US20060246044A1 - Methods for improving cell therapy and tissue regeneration in patients with cardiovascular and neurological diseases by means of shockwaves - Google Patents

Methods for improving cell therapy and tissue regeneration in patients with cardiovascular and neurological diseases by means of shockwaves Download PDF

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US20060246044A1
US20060246044A1 US11/304,865 US30486505A US2006246044A1 US 20060246044 A1 US20060246044 A1 US 20060246044A1 US 30486505 A US30486505 A US 30486505A US 2006246044 A1 US2006246044 A1 US 2006246044A1
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patient
tissue
cells
progenitor cells
shock waves
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Andreas Lutz
Harald Eizenhofer
Andreas Zeiher
Stefanie Dimmeler
Christopher Heeschen
Alexandra Aicher
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Dornier Medtech Systems GmbH
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Dornier Medtech Systems GmbH
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Publication of US20060246044A1 publication Critical patent/US20060246044A1/en
Priority to US12/214,660 priority patent/US9060915B2/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61H—PHYSICAL THERAPY APPARATUS, e.g. DEVICES FOR LOCATING OR STIMULATING REFLEX POINTS IN THE BODY; ARTIFICIAL RESPIRATION; MASSAGE; BATHING DEVICES FOR SPECIAL THERAPEUTIC OR HYGIENIC PURPOSES OR SPECIFIC PARTS OF THE BODY
    • A61H23/00—Percussion or vibration massage, e.g. using supersonic vibration; Suction-vibration massage; Massage with moving diaphragms
    • A61H23/008—Percussion or vibration massage, e.g. using supersonic vibration; Suction-vibration massage; Massage with moving diaphragms using shock waves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B17/22004—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/44—Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1858—Platelet-derived growth factor [PDGF]
    • A61K38/1866—Vascular endothelial growth factor [VEGF]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/195—Chemokines, e.g. RANTES
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/00234—Surgical instruments, devices or methods, e.g. tourniquets for minimally invasive surgery
    • A61B2017/00238—Type of minimally invasive operation
    • A61B2017/00243—Type of minimally invasive operation cardiac
    • A61B2017/00247—Making holes in the wall of the heart, e.g. laser Myocardial revascularization
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00315—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for treatment of particular body parts
    • A61B2018/00345—Vascular system
    • A61B2018/00351—Heart
    • A61B2018/00392—Transmyocardial revascularisation

Definitions

  • the present invention relates to methods for improving cell therapy in a patient. More specifically, the present invention relates to methods for improving cell therapy in patient who is suffering from a cardiovascular or a neurological disease by using shock waves as a therapeutic tool for targeting the recruitment of stem cells and/or progenitor cells to a tissue of the patient.
  • Stem and progenitor cells derived from the bone marrow may play a role in ongoing endothelial repair (Kalka et al., 2000). Impaired mobilization or depletion of these cells may contribute to endothelial dysfunction and cardiovascular disease progression. Indeed, in healthy men, levels of circulating progenitor cells may be a surrogate biologic marker for vascular function and cumulative cardiovascular risk. Recent advances in basic science have also established a fundamental role for endothelial stem and progenitor cells in postnatal neovascularization and cardiac regeneration. Improvement of neovascularization after critical ischemia is an important therapeutic option after myocardial infarction or limb ischemia.
  • angiogenesis neovascularization of ischemic tissue in the adult was believed to be restricted to migration and proliferation of mature endothelial cells, a process termed “angiogenesis”.
  • increasing evidence suggests that circulating stem and progenitor cells home to sites of ischemia and contribute to the formation of new blood vessels.
  • this process is referred to as “vasculogenesis”.
  • the importance of circulating stem and progenitor cells is demonstrated by the fact that genetic inhibition of their recruitment inhibits tumor angiogenesis.
  • VEGF vascular endothelial growth factor
  • SDF-1 stromal cell-derived factor
  • the present inventors have recently shown that infusion of bone marrow mononuclear cells derived from patients with ischemic heart disease is significantly less effective in improving perfusion of ischemic tissue in a hind limb ischemia animal model. Moreover, bone marrow cells of patients with ischemic heart disease reveal a reduced colony forming activity and an impairment of migratory response towards VEGF and SDF-1, which are potent chemoattractive and mobilizing agents (Heeschen C et al., Circulation 2004; 109(13): 1615-22.) Moreover, the present inventors were also able to demonstrate that in experimental models of tissue ischemia, recruitment of systemically infused stem/progenitor cells is significantly lower as compared to the recruitment of stem/progenitor cells derived from healthy donors.
  • Extracorporeal shock waves are generated by high voltage spark discharge under water. This causes an explosive evaporation of water, producing high energy acoustic waves. By focusing the acoustic waves with a semi-ellipsoid reflector, the waves can be transmitted to a specific tissue site (Ogden et al., 2001). ESW have been found beneficial in certain orthopedic conditions. The interactions of ESW with the targeted tissue are manifold: mechanical forces at tissue interfaces related to different acoustic impedances, as well as micro-jets of collapsing cavitation bubbles are the primary effects. However, the cellular and biochemical mechanisms, by which these physical effects may enhance healing of fractures, remain to be determined. It has been scintigraphically and sonographically implicated that local blood flow and metabolism of bone and Achilles tendon are positively affected by ESW treatment (Maier et al., 2002).
  • ESW therapy has shown to be effective in the treatment of orthopedic conditions including non-union of long bone fracture, calcifying tendonitis of the shoulder, lateral epicondylitis of the elbow, proximal plantar fasciitis, and Achilles tendonitis (Kruger et al., 2002).
  • the success of shock wave therapy ranges from 80% for non-unions of long bone fractures to 15-90% for tendinopathies of the shoulder, elbow and heel.
  • the short-term results of shock wave therapy for avascular necrosis of the femoral head appear encouraging.
  • Shock wave therapy also showed a positive effect in promoting bone healing in animal experiments. Despite the success in clinical application, the exact mechanism of shock wave therapy remains unknown.
  • shock wave therapy enhanced neovascularization at the tendon-bone junction (Wang et al., 2002). It was hypothesized that shock wave therapy may have the potential to induce the ingrowth of new blood vessels and improvement of blood supply that lead to tissue regeneration. Indeed, a recent study in rabbits showed that shock wave therapy induces the ingrowth of neovessels and tissue proliferation associated with the early release of angiogenesis-related factors including endothelial nitric oxide synthase (eNOS) and VEGF at the tendon-bone junction in rabbits (Wang et al., 2003).
  • eNOS endothelial nitric oxide synthase
  • VEGF vascular endothelial nitric oxide synthase
  • the mechanism of shock wave therapy may involve the early release of angiogenic growth factors and subsequent induction of cell proliferation and formation of neovessels at the tendon-bone junction.
  • the occurrence of neovascularization may lead to the improvement of blood supply and play a role in tissue regeneration at the tendon-bone junction.
  • ESW therapy ameliorates ischemia-induced myocardial dysfunction in pigs in vivo (Nishida et al., 2004).
  • post infarction heart failure remains a major cause of morbidity and mortality in patients with coronary heart disease.
  • ventricular remodeling processes characterized by progressive expansion of the infarct area and dilation of the left ventricular cavity result in the development of heart failure in a sizeable fraction of patients surviving an acute myocardial infarction.
  • the major goal to reverse remodeling would be the stimulation of neovascularization as well as the enhancement of regeneration of cardiac myocytes within the infarct area.
  • Peripheral neuropathy describes damage to the peripheral nerves. It may be caused by diseases of the nerves or as the result of systemic illnesses. Many neuropathies have well-defined causes such as diabetes, uremia, AIDS, or nutritional deficiencies. In fact, diabetes is one of the most common causes of peripheral neuropathy. Other causes include mechanical pressure such as compression or entrapment, direct trauma, fracture or dislocated bones; pressure involving the superficial nerves (ulna, radial, or peroneal); and vascular or collagen disorders such as atherosclerosis, systemic lupus erythematosus, scleroderma, and rheumatoid arthritis.
  • peripheral neuropathy Although the causes of peripheral neuropathy are diverse, they produce common symptoms including weakness, numbness, paresthesia (abnormal sensations such as burning, tickling, pricking or tingling) and pain in the arms, hands, legs and/or feet. A large number of cases are of unknown cause.
  • Therapy for peripheral neuropathy differs depending on the cause.
  • therapy for peripheral neuropathy caused by diabetes involves control of the diabetes.
  • treatment may consist of splinting or surgical decompression of the ulnar or median nerves.
  • Peroneal and radial compression neuropathies may require avoidance of pressure.
  • Physical therapy and/or splints may be useful in preventing contractures (a condition in which shortened muscles around joints cause abnormal and sometimes painful positioning of the joints).
  • Ischemic peripheral neuropathy is a frequent, irreversible complication of lower extremity vascular insufficiency. It has been shown that ischemic peripheral neuropathy can be prevented and/or reversed by gene transfer of an endothelial cell mitogen (e.g. VEGF) designed to promote therapeutic angiogenesis (Schratzberger P, et al.). The major goal to reverse vascular insufficiency would thus be the stimulation of angiogenesis and the regeneration of the vascular tissue within the area affect by peripheral neuropathy.
  • an endothelial cell mitogen e.g. VEGF
  • the technical problem underlying the present invention in thus to enhance the cell therapy and regeneration of tissues affected by a cardiovascular or a neurological disease.
  • this problem is solved by the provision of a method for improving cell therapy in a patient suffering from a cardiovascular disease or a neurological disease comprising a treatment by means of shock waves of an tissue of the patient affected by the disease, which tissue is targeted for cell therapy.
  • the present invention provides, in part, a therapeutic tool improving the targeted recruitment of stem and progenitor cells in patients undergoing cell therapy.
  • the present invention relates to methods for improving cell therapy in a patient who is suffering from a cardiovascular or a neurological disease and is undergoing cell therapy by using shock waves as a therapeutic tool for targeting the recruitment of stem cells and/or progenitor cells to a tissue of the patient.
  • the present invention also relates to methods for improving tissue regeneration in a patient suffering from a cardiovascular or neurological disease by treating a tissue of the patient affected by the disease using shock waves.
  • methods for treating a cardiovascular or neurological disease in a patient comprising the treatment of a tissue of the patient affected by the disease by means of shock waves, and applying to the patient a therapeutically effective amount of stem cells and/or progenitor cells.
  • the present invention further also relates to the use of stem cells and/or progenitor cells for preparing a pharmaceutical composition for treating a patient suffering from a cardiovascular disease or a neurological disease, wherein the patient is subjected to a treatment with shock waves before, during, or after administration of the stem cells and/or progenitor cells.
  • the present inventors have recently shown that autologous stem and progenitor cells in patients with cardiovascular risk factors have a reduced ability to home and migrate to damaged tissue. Since the expression of chemoattractant factors in chronically injured tissue is markedly reduced as compared to acute injury, the overall recruitment of stem/progenitor cells in patients with cardiovascular risk factors is impaired.
  • the invention involves the treatment of tissue that is targeted for therapy with stem and progenitor cells by means of shock waves to increase the expression of chemoattractants (i.e. factors mediating the attraction of circulating stem and progenitor cells, e.g. SDF-1 ⁇ , VEGF, P1GF) and pro-angiogenic factors (i.e.
  • pro-survival factors i.e. factors stimulating pre-existing endothelial cells to form new vessels
  • pro-survival factors i.e. factors inhibiting apoptosis/programmed cell death, e.g. HGF, IGF, VEGF.
  • the increased expression of chemoattractant and pro-angiogenic factors will improve the recruitment of systemically infused stem and/or progenitor cells, and enhanced expression of pro-survival factors will improve the microenvironment for cells directly administered into the target tissue.
  • the homing of stem and progenitor cells will be enhanced. Thereby, shock wave treatment of the targeted tissue will enhance the therapeutic effect of cell therapy.
  • ESW extracorporeal shock waves
  • stem cells and/or progenitor cells By combining the application of extracorporeal shock waves (“ESW”) and the application of stem cells and/or progenitor cells, the regeneration of cardiovascular and neurological diseases may be improved.
  • the combination of ESW and the application of stem cells and/or progenitor cells may be used to treat cardiovascular and neurological diseases.
  • FIG. 1 is a block diagram depicting shock wave-induced vascular endothelial growth factor (“VEGF”) expression in rat hindlimb muscles detected by Western blot, according to an exemplary embodiment of the invention.
  • VEGF vascular endothelial growth factor
  • FIG. 2A is a representative image of shock wave-induced VEGF expression in rat hind limb muscles detected by VEGF staining on frozen sections, according to an exemplary embodiment of the invention.
  • FIG. 2B is a block diagram depicting shock wave-induced VEGF expression in rat hind limb muscles detected by VEGF staining on frozen sections, according to an exemplary embodiment of the invention.
  • FIG. 3A is a representative image of detection of intravenously injected endothelial progenitor cells (“EPCs”) after shock wave treatment, wherein 10- ⁇ m frozen sections were analyzed for EPCs (red fluorescence) and nuclei were stained with Tropro-3 (blue fluorescence), according to an exemplary embodiment of the invention.
  • EPCs endothelial progenitor cells
  • FIG. 3B is a block diagram depicting quantification of intravenously injected EPCs that were recruited to shock wave treated muscles, according to an exemplary embodiment of the invention.
  • FIG. 4A is a series of representative images of the ischemic (left) and non-ischemic (right) limb for animals that received either no treatment, EPC infusion only, shock wave pretreatment only, or both, according to an exemplary embodiment of the invention.
  • FIG. 4B is a block diagram depicting quantitative perfusion data generated by calculating the ratio of the perfusion of the ischemic to the non-ischemic limb, according to an exemplary embodiment of the invention.
  • the invention is related to a method for improving cell therapy in a patient suffering from a cardiovascular disease or a neurological disease comprising a treatment by means of shock waves of a tissue of the patient affected by the disease, which tissue is targeted for cell therapy.
  • the invention in another aspect, relates to a method for improving the tissue regeneration in a patient suffering from a cardiovascular disease or a neurological disease comprising the steps of treating a tissue of the patient affected by the disease by means of shock waves, and applying to the patient a therapeutically effective amount of stem cells and/or progenitor cells.
  • the invention is related to a method for treating a cardiovascular disease or a neurological disease in a patient comprising the steps of treating a tissue of the patient affected by the disease by means of shock waves, and applying to the patient a therapeutically effective amount of stem cells and/or progenitor cells.
  • the treatment of the patient by shock waves is carried out prior to the administration of the stem and/or progenitor cells.
  • a simultaneous application of both shock waves and stem/progenitor cells and a subsequent application of shock waves is also contemplated.
  • the invention relates to a use of stem and/or progenitor cells for preparing a pharmaceutical composition for treating a patient suffering from a cardiovascular disease or neurological disease, wherein the patient is subjected to a treatment with shock waves before, during, or after administration of the stem and/or progenitor cells.
  • cell therapy refers to the transplantation of cells to replace or repair damaged tissue and/or cells.
  • Cell therapy involves the use of blood transfusions and bone marrow transplants, as well as injections of cellular materials.
  • shock waves is used interchangeably with the term “acoustical pressure pulse”.
  • stem cell refers to an unspecialised cell that is capable of replicating or self-renewing itself and developing into specialized cells of a variety of cell types.
  • the product of a stem cell undergoing division is at least one additional cell that has the same capabilities as the original cell.
  • stem cell is intended to encompass embryonal and adult stem cells, totipotent and pluripotent cells, and autologous cells, as well as heterologous cells.
  • progenitor cell also known as a precursor cell
  • progenitor cell is intended to encompass cells which are yet undifferentiated but may already be committed to a specific cell type (e.g. endothelial progenitor cells are committed to differentiate into endothelial cells).
  • the patient's disease is a cardiovascular disease.
  • the cardiovascular disease has a non-ischemic etiology.
  • An example of a cardiovascular disease with a non-ischemic etiology which can be treated by the methods according to the invention is dilatative cardiomyopathy.
  • the cardiovascular disease may have an ischemic etiology.
  • Cardiovascular diseases with an ischemic etiology which may be improved by cell therapy include myocardial infarctions and ischemic cardiomyopathies. Chronic ischemic cardiomyopathy is particularly preferred.
  • the patient's disease is a neurological disease.
  • the neurological disease is peripheral neuropathy or neuropathic pain.
  • the affected tissue is located in the heart or in a skeletal muscle.
  • chemoattractant factor is used herein to refer to a factor activating the movement of individual cells, in response to a chemical concentration gradient.
  • the at least one chemoattractant factor is vascular endothelial growth factor, VEGF, or stromal cell derived factor 1, SDF-1.
  • the shock waves used in the methods and uses according to the invention preferably are extracorporeal shock waves which may, for instance, be applied extra-thoracal.
  • extracorporeal shock waves delivered e.g. trans-esophageal
  • endoscopic shock waves delivered e.g. intraluminal such as in the artery
  • the shock waves may be applied during open surgery (intra-operative).
  • shocks per area and/or a total number of 100, 250, 500, 1000, or 1500 shocks per treatment are applied.
  • shocks with an energy of 0.05, 0.09, 0.13; 0.22, 0.36, or 0.50 mJ/mm 2 are applied.
  • the shock waves may be applied once or several times prior to cell therapy; an application once or twice prior to cell therapy is preferred.
  • the shock waves are applied several hours before the start of the cell therapy; an application 24 h, 36 h, or 48 h prior to cell injection is particularly preferred.
  • the shock waves may be exclusively or additionally be applied during cell therapy and/or after the start of the cell therapy.
  • the stem and/or progenitor cells which are used in the methods and uses according to the invention are embryonic or umbilical cord-blood derived cells.
  • the stem and/or progenitor cells are adult cells.
  • Adult stem and/or progenitor cells can be derived from bone marrow, peripheral blood, and organs.
  • the cells can be derived from healthy donors or patients suffering from coronary heart disease.
  • the stem and/or progenitor cells are isolated and, optionally, cultivated ex vivo before being applied.
  • stem and/or progenitor cells may be used in the methods and uses according to the invention:
  • CD34-CD45 ⁇ bone marrow-derived mesenchymal stem cells (MSC)
  • stage-specific embryonic antigen SSEA-4+Oct4+ embryonic stem cells
  • CD34+CD45+ cord blood-derived stem cells CD34+CD45+ cord blood-derived stem cells.
  • the stem and/or progenitor cells used in the methods and uses according to the invention may be applied by way of systemic infusion, local arterial infusion, venous infusion, and/or by direct injection into the affected tissue.
  • the cells may further be encapsulated in microspheres (targeted drug delivery). Contrast agents used for ultrasound are examples for useful encapsulation agents.
  • the cells may then be released from the microspheres at the targeted tissue using ultrasound (acoustic energy).
  • a prerequisite for the success of cell therapy is the homing and, thus, engraftment of transplanted cells into the target area, especially if an intravascular route of administration is chosen.
  • the present inventors have now shown that the migratory capacity of adult progenitor cells towards their physiological chemo-attractant reflects their homing capacity into the ischemic/infarcted area.
  • enhancing the recruitment of stem/progenitor cells is a novel target for improving the clinical outcome after autologous cell therapy in aged individuals and patients with cardiovascular risk factors;
  • peripheral blood was freshly drawn and collected in heparin monovettes (10 ml).
  • Dulbecco's Phosphate Buffered Saline without calcium and magnesium (Cat. No. H-15-002) was used for suspension of the cells for injection.
  • PAA was purchased from Laboratories GmbH (Pasching, Austria).
  • Fetal Bovine Serum (Cat. No.
  • Mononuclear cells are separated from freshly collected peripheral blood or buffy coats from the blood donation center using Ficoll gradient centrifugation.
  • 15 ml Biocoll separation solution are provided per 50 ml tube.
  • the peripheral blood (PB) is diluted with PBS (PB 1:1 or buffy coats 1:4).
  • 25 ml of the diluted blood are overlayed on 15 ml of the Biocoll separation solution.
  • the tube is centrifugated at 800 ⁇ g for 20 min at room temperature without brake. This is an important step to separate the mononuclear cells (in the interphase) from erythrocytes and granulocytes (pellet) and platelets in the upper serum phase.
  • wells are coated with 10 ⁇ g/ml human fibronectin in PBS, and the wells are incubated for at least 30 min at room temperature.
  • the mononuclear cells are pipetted from the interphase carefully in a new 50 ml tube.
  • PBS is added to 50 ml to wash the cells.
  • the cells were centrifugated at 800 ⁇ g for 10 min at room temperature (with brake). The supernatant was removed and the cell pellet was resuspended in 50 ml PBS.
  • the cells were centrifugated at 800 ⁇ g for 10 min at room temperature (with brake), the supernatant was removed and the cell pellet was resuspended in 10 ml PBS.
  • the supernatant is removed and the cell pellet is resuspended in culture medium (endothelial basal medium supplemented with 20% FBS, epidermal growth factor (10 ⁇ g/mL), bovine brain extract (3 ⁇ g/mL), gentamicin (50 ⁇ g/mL), hydrocortisone (1 ⁇ g/mL), VEGF (100 ng/ml) to a cell concentration of 8 ⁇ 10 6 cells/ml medium.
  • Fibronectin is then removed from the dishes.
  • the cells are added to the fibronectin-coated wells at a density of approx.
  • EPCs adherent endothelial progenitor cells
  • EPCs were washed with PBS, trypsinized for 2 min, then the reaction was stopped with serum-containing RPMI medium. Detached EPCs were washed again with PBS, incubated with CM-Dil (Molecular Probes) diluted in PBS (1:100) for 5 min at 37° C., followed by incubation for 15 min on ice. After washing, 1 ⁇ 10 6 CM-Dil-labeled EPCs were injected into the jugular vein of nude rats pre-treated with shock wave therapy.
  • CM-Dil Molecular Probes
  • Shock waves were applied at graded doses of flux density (0.13-0.64 mJ/mm 2 ; 3 Hz; 500 impulses) to the upper right hind limb of nude rats. The energy was focused on the upper limb, while moving the focus distally for 2 mm after every 100 impulses.
  • shock wave treatment up-regulates pro-angiogeneic growth factors such as VEGF, which is chemoattractant for VEGF receptor 1 or 2 positive stem and progenitor cells that are injected after 24 h.
  • VEGF pro-angiogeneic growth factors
  • the right hind limb of nude rats was treated with a flux density of 0.13, 0.22, 0.43, and 0.64 mJ/mm 2 ( FIG. 1 ).
  • the left hind limb was used as a negative control (0 mJ/mm 2 ).
  • the shock wave-induced up-regulation of VEGF protein expression was analyzed in the treated versus the untreated hind limb by means of Western blotting.
  • rats were sacrificed and the adductor muscle of the right and left hind limbs were removed, frozen in liquid nitrogen, and minced in a mortar using 1 ml protein lysis buffer (20 mmol/L Tris (pH 7.4), 150 mmol/L NaCl, 1 mmol/L EDTA, 1 mmol/L EGTA, 1% Triton, 2.5 mmol/L sodium pyrophosphate, 1 mmol/L ⁇ -glycerophosphate, 1 mmol/L Na3VO4, 1 ⁇ g/mL leupeptin and 1 mmol/L phenylmethylsulfonyl fluoride) for 15 min on ice.
  • 1 ml protein lysis buffer (20 mmol/L Tris (pH 7.4), 150 mmol/L NaCl, 1 mmol/L EDTA, 1 mmol/L EGTA, 1% Triton, 2.5 mmol/L sodium pyrophosphate, 1 mmol/L ⁇
  • VEGF expression was detected as cytoplasmic and secreted VEGF staining (green fluorescence) with respect to nuclear staining (blue fluorescence). Since flux densities higher than 0.43 mJ/mm 2 led to high unspecific background levels of VEGF expression, only flux densities between 0.13 mJ/mm 2 and 0.43 mJ/mm 2 were used ( FIG. 2 b ).
  • VEGF + cells per high power (HP) view was determined for 0.13, 0.22, and 0.43 mJ/mm 2 .
  • EPCs were labeled with a red fluorescent cell tracker and infused intravenously 24 h after shock wave therapy of the right hind limb. Since the best results for VEGF staining in cyrosections had been obtained using energy of 0.43 mJ/mm 2 , the following experiments were performed using the same flux density.
  • CM-Dil + (red fluorescent) human EPCs (1 ⁇ 10 6 ) were intravenously injected. The animals were sacrificed after 72 h and the tissue was evaluated for red fluorescent EPCs incorporated into vessel structures. The number of red fluorescent cells in the shock wave-treated right versus the untreated left hind limb was analysed.
  • Hind limb ischemia model The in vivo neovascularization capacity of infused human EPC was investigated in a rat model of hind limb ischemia, by use of 5 wk old athymic nude rats (Charles River Laboratory) weighing 100-120 g. The proximal portion of the femoral artery including the superficial and the deep branch as well as the distal portion of the saphenous artery were occluded using an electrical coagulator. The overlying skin was closed using surgical staples. Three weeks after induction of hind limb ischemia, chronic ischemia was assessed by Laser Doppler imaging. Only rats with evidence for chronic ischemia were randomized for one of the four treatment groups: Shock wave Group pretreatment EPC infusion 1 ⁇ ⁇ 2 ⁇ + 3 + ⁇ 4 + + +
  • EPCs were infused 24 hours after shock wave pretreatment.
  • the ischemic (right)/non-ischemic (left) limb blood flow ratio was determined using a laser Doppler blood flow imager (Laser Doppler Perfusion Imager System, moorLDITM-Mark 2, Moor Instruments, Wilmington, Del.). Before initiating scanning, mice were placed on a heating pad at 37° C. to minimize variations in temperature. After twice recording laser Doppler color images, the average perfusions of the ischemic and non-ischemic limb were calculated. To minimize variables including ambient light and temperature, calculated perfusion is expressed as the ratio of ischemic to non-ischemic hind limb perfusion.
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Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070142753A1 (en) * 2005-03-04 2007-06-21 General Patent Llc Pancreas regeneration treatment for diabetics using extracorporeal acoustic shock waves
US20100056849A1 (en) * 2006-11-30 2010-03-04 Miracor Medical Systems Gmbh Method and device for the intermittent occlusion of a vein draining the organ system
US20110034832A1 (en) * 2009-07-08 2011-02-10 Iulian Cioanta Usage of Extracorporeal and Intracorporeal Pressure Shock Waves in Medicine
US20130197404A1 (en) * 2012-01-27 2013-08-01 Avner Spector Method for imporoving kidney function with extracorporeal shockwaves
US20170296427A1 (en) * 2016-04-18 2017-10-19 General Patent, Llc Treatments for blood sugar levels and muscle tissue optimization using extracorporeal acoustic shock waves
US9855049B2 (en) 2013-12-11 2018-01-02 Miracor Medical Systems Gmbh System and method for treating heart tissue
US20200269073A1 (en) * 2019-02-22 2020-08-27 Creative Medical Technologies, Inc. Extracorporeal shock wave ultrasound for enhancement of regenerative activities in erectile dysfunction
US20210153885A1 (en) * 2012-01-27 2021-05-27 Avner Spector Method of treatment with low energy extracorporeal shockwaves
US11389373B2 (en) 2016-04-18 2022-07-19 Softwave Tissue Regeneration Technologies, Llc Acoustic shock wave therapeutic methods to prevent or treat opioid addiction
US11389371B2 (en) 2018-05-21 2022-07-19 Softwave Tissue Regeneration Technologies, Llc Acoustic shock wave therapeutic methods
US11389372B2 (en) 2016-04-18 2022-07-19 Softwave Tissue Regeneration Technologies, Llc Acoustic shock wave therapeutic methods
US11458069B2 (en) 2016-04-18 2022-10-04 Softwave Tissue Regeneration Technologies, Llc Acoustic shock wave therapeutic methods to treat medical conditions using reflexology zones

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10234144A1 (de) * 2002-07-26 2004-02-05 Dornier Medtech Gmbh Lithotripter
DE102005037043C5 (de) * 2005-08-05 2017-12-14 Dornier Medtech Systems Gmbh Stoßwellentherapiegerät mit Bildgewinnung
US9669200B2 (en) 2010-08-06 2017-06-06 Boston Scientific Scimed, Inc. Systems and methods for the treatment of pelvic disorders including magnetic particulates
US9180172B2 (en) 2010-12-15 2015-11-10 Ams Research Corporation Treatment of Peyronies disease
US8979797B2 (en) 2010-12-16 2015-03-17 Ams Research Corporation High pressure delivery system and method for treating pelvic disorder using large molecule therapeutics
KR101303914B1 (ko) * 2011-04-26 2013-09-05 윤종규 허혈성 심질환 치료용 충격파 발생 장치
CN106138415A (zh) * 2016-09-08 2016-11-23 四川聚豪生物科技有限公司 一种用于各种原因导致的股骨头坏死的中药组合物
CN110982779B (zh) * 2019-12-25 2020-12-29 广州市天河诺亚生物工程有限公司 一种提高脐带血利用率的方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2707391A (en) * 1951-10-23 1955-05-03 Bell Telephone Labor Inc Testing viscous liquids
US3934458A (en) * 1974-02-04 1976-01-27 Technicon Instruments Corporation Method and apparatus for pulse echo imaging
US4240285A (en) * 1978-08-09 1980-12-23 The Marconi Company Limited Measurement of the density of liquids
US4712037A (en) * 1985-07-03 1987-12-08 Nederlandse Centrale Organisatie Voor Toegepast-Natuurwetenschappelijk Onderzoek Resonant piezoelectric sensor
US6039565A (en) * 1997-01-14 2000-03-21 Chou; Marilyn M. Combined ultrasonic and laser device and method of use

Family Cites Families (165)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US48847A (en) 1865-07-18 Improvement in vessels for reception and transportation of night-soil
US1750129A (en) 1926-10-12 1930-03-11 Hudson Motor Car Co Automobile body handling
US2324702A (en) 1938-11-30 1943-07-20 Karl F Hoffmann Surgical simulacra and process of preparing same
US2578505A (en) 1948-03-02 1951-12-11 Sperry Prod Inc Supersonic agitation
DE1011800B (de) 1953-07-03 1957-07-04 Leo Torsten Ulfstedt Verfahren zur Haertung grossporiger, erstarrter Erzeugnisse
US4189026A (en) 1954-01-13 1980-02-19 The United States Of America As Represented By The Secretary Of The Navy Underwater generation of low frequency sound
US2859726A (en) 1954-06-24 1958-11-11 John V Bouyoncos Acoustic-vibration coupler
US3056312A (en) 1957-09-19 1962-10-02 Gen Motors Corp Dynamic vibration absorber
US3249177A (en) 1961-11-13 1966-05-03 Bolt Associates Inc Acoustic wave impulse generator repeater
US3406302A (en) 1966-03-15 1968-10-15 Westinghouse Electric Corp Cylindrical magnetostrictive electromechanical transducer
US3505880A (en) 1967-01-20 1970-04-14 Singer General Precision Pneumatic vibratory digital sensors
US3538919A (en) 1967-04-07 1970-11-10 Gregory System Inc Depilation by means of laser energy
US3555880A (en) 1967-04-12 1971-01-19 Industrial Nucleonics Corp Liquid density measuring system
US3556928A (en) 1967-06-09 1971-01-19 Cincinnati Milacron Inc Copper-clad plastic panel
US3588801A (en) 1968-11-07 1971-06-28 Willie B Leonard Impulse generator
CH537045A (de) * 1970-08-13 1973-05-15 Eckardt Ag J Pneumatischer Regler
US3783403A (en) 1972-09-22 1974-01-01 Trw Inc Double pulse laser
DE2346649A1 (de) 1973-09-17 1975-03-27 Ngk Spark Plug Co Ultraschallgeber
US3997853A (en) 1974-11-29 1976-12-14 Allied Chemical Corporation Chromium-doped beryllium aluminate lasers
IT1117550B (it) 1977-08-01 1986-02-17 Righini Giancarlo Sistema di trasporto e di focalizzazione della radiazione laser con fibra ottica particolarmente per applicazioni mediche chirurgiche e biologiche
US4369100A (en) 1977-09-27 1983-01-18 Sawyer Harold T Method for enhancing chemical reactions
US4207874A (en) 1978-03-27 1980-06-17 Choy Daniel S J Laser tunnelling device
US4272733A (en) 1978-10-20 1981-06-09 Allied Chemical Corporation Broadly tunable chromium-doped beryllium aluminate lasers and operation thereof
US4336858A (en) 1978-11-03 1982-06-29 General Electric Company Braking system for a medical diagnostic device
US4286168A (en) 1979-01-18 1981-08-25 Atomic Products Corp. Phantom simulation device for scintillation cameras
US4286455A (en) 1979-05-04 1981-09-01 Acoustic Standards Corporation Ultrasound phantom
US4336809A (en) 1980-03-17 1982-06-29 Burleigh Instruments, Inc. Human and animal tissue photoradiation system and method
US4494622A (en) 1981-01-05 1985-01-22 Thompson David L Motorcycle power transmission and brake assembly
DE3119295A1 (de) 1981-05-14 1982-12-16 Siemens AG, 1000 Berlin und 8000 München Einrichtung zum zerstoeren von konkrementen in koerperhoehlen
EP0068961A3 (de) 1981-06-26 1983-02-02 Thomson-Csf Vorrichtung zur lokalen Erwärmung von biologischen Gewebe
DE3240691C1 (de) 1982-11-04 1987-12-23 Dornier System Gmbh, 7990 Friedrichshafen Vorrichtung zur Erzeugung von Stosswellenimpulsfolgen
US4546960A (en) 1983-06-20 1985-10-15 Gould Inc. Vibration isolation assembly
US4493653A (en) 1983-09-27 1985-01-15 Technicare Corporation Biopsiable ultrasound phantom
US4672969A (en) 1983-10-06 1987-06-16 Sonomo Corporation Laser healing method
US4642611A (en) 1983-10-14 1987-02-10 Koerner Andre F Sound engine
FR2563725B1 (fr) 1984-05-03 1988-07-15 Dory Jacques Appareil d'examen et de localisation de tumeurs par ultrasons muni d'un dispositif de traitement localise par hyperthermie
US5143073A (en) 1983-12-14 1992-09-01 Edap International, S.A. Wave apparatus system
US6203777B1 (en) 1983-12-21 2001-03-20 Nycomed Imaging As Method of contrast enhanced magnetic resonance imaging using carbohydrate particles
US4639923A (en) 1984-05-21 1987-01-27 Cornell Research Foundation, Inc. Optical parametric oscillator using urea crystal
US4693244A (en) 1984-05-22 1987-09-15 Surgical Laser Technologies, Inc. Medical and surgical laser probe I
US4620546A (en) 1984-06-30 1986-11-04 Kabushiki Kaisha Toshiba Ultrasound hyperthermia apparatus
US4580559A (en) 1984-07-24 1986-04-08 Esperance Francis A L Indirect ophthalmoscopic photocoagulation delivery system for retinal surgery
DE3443295A1 (de) 1984-11-28 1986-06-05 Wolfgang Prof. Dr. 7140 Ludwigsburg Eisenmenger Einrichtung zur beruehrungsfreien zertruemmerung von konkrementen im koerper von lebewesen
US4641912A (en) 1984-12-07 1987-02-10 Tsvi Goldenberg Excimer laser delivery system, angioscope and angioplasty system incorporating the delivery system and angioscope
US4807626A (en) 1985-02-14 1989-02-28 Mcgirr Douglas B Stone extractor and method
US4671254A (en) 1985-03-01 1987-06-09 Memorial Hospital For Cancer And Allied Diseases Non-surgical method for suppression of tumor growth
US5067493A (en) 1985-05-24 1991-11-26 Elscint Ltd. Lithotripsy system using ultrasound to locate calculi
DE3617032C2 (de) 1985-05-24 1997-06-05 Elscint Ltd Lithotripsiegerät mit extrakorporalem Stoßwellengenerator
US4813402A (en) 1986-02-19 1989-03-21 Siemens Aktiengesellschaft Coupling member for a shock wave therapy device
DE3607949A1 (de) 1986-03-11 1987-09-17 Wolf Gmbh Richard Verfahren zum erkennen von moeglichen gewebeschaedigungen bei der medizinischen anwendung von hochenergie-schall
US4829986A (en) 1986-08-22 1989-05-16 Siemens Aktiengesellschaft Lithotripsy work station
DE3723815A1 (de) 1986-11-29 1988-06-09 Hoffmann Medizinische Technik Verfahren und vorrichtung zur eliminierung traumatischer effekte bei der nierensteinzertruemmerung
US4798196A (en) 1986-12-16 1989-01-17 Trutek Research, Inc. Shroud for coupling kidney stone disintegrator to human body
DE3703335C2 (de) 1987-02-04 1996-04-18 Siemens Ag Lithotripter mit PVDF-Folie als Ortungselement
DE3703338A1 (de) 1987-02-04 1988-08-18 Siemens Ag Lithotripter mit integrierter ortungsvorrichtung
US4756016A (en) 1987-03-06 1988-07-05 John K. Grady Asymmetric X-ray stand
DE8710118U1 (de) 1987-07-23 1988-11-17 Siemens Ag, 1000 Berlin Und 8000 Muenchen, De
US5209221A (en) 1988-03-01 1993-05-11 Richard Wolf Gmbh Ultrasonic treatment of pathological tissue
DE3817726A1 (de) 1988-05-25 1989-11-30 Siemens Ag Vorrichtung zur raeumlichen ultraschall-ortung von konkrementen
DE3830183A1 (de) 1988-09-06 1990-03-15 Philips Patentverwaltung Verfahren zum positionieren eines auf einer tischplatte eines lagerungstisches befindlichen patienten und geraet zum durchfuehren des verfahrens
DE3835318C1 (de) 1988-10-17 1990-06-28 Storz Medical Ag, Kreuzlingen, Ch
DE68921154T2 (de) 1988-11-15 1995-09-28 Bruno Germain Einschalige Mehrzweckvorrichtung zum Demontieren und abgedichteten Lagern von medizinischen und chirurgischen Instrumenten.
DE3840077A1 (de) 1988-11-28 1990-05-31 Wolf Gmbh Richard Lithotriptor
US5149030A (en) 1988-12-23 1992-09-22 Summa A.N.T.S. Advanced neonatal transport system
JP2694992B2 (ja) 1989-02-17 1997-12-24 株式会社東芝 結石破砕装置
JP3011414B2 (ja) 1989-02-28 2000-02-21 株式会社東芝 結石破砕装置
DE3916093A1 (de) 1989-05-17 1990-11-22 Wolf Gmbh Richard Lithotriptor
DE3917858A1 (de) 1989-06-01 1990-12-06 Dornier Medizintechnik Koppelflaeche fuer einen lithotripter
DE3919083C1 (de) 1989-06-10 1990-06-21 Dornier Medizintechnik Gmbh, 8000 Muenchen, De
US5435311A (en) 1989-06-27 1995-07-25 Hitachi, Ltd. Ultrasound therapeutic system
DK168302B1 (da) 1989-06-29 1994-03-07 Danisco Fremgangsmåde til indføring af molekyler, især genetisk materiale i planteceller
DE3921808A1 (de) 1989-07-03 1991-01-17 Schubert Werner Vorrichtung zur fokussierten stosswellenbehandlung von tumoren
US5065761A (en) 1989-07-12 1991-11-19 Diasonics, Inc. Lithotripsy system
DE3942253A1 (de) 1989-12-21 1991-06-27 Dornier Medizintechnik Halterung eines diagnostischen ultraschall-transducers
US5542935A (en) 1989-12-22 1996-08-06 Imarx Pharmaceutical Corp. Therapeutic delivery systems related applications
US6088613A (en) 1989-12-22 2000-07-11 Imarx Pharmaceutical Corp. Method of magnetic resonance focused surgical and therapeutic ultrasound
US5072960A (en) 1990-02-15 1991-12-17 Sterilizer Technologies Corporation Sterilizer cart
JP3065634B2 (ja) 1990-03-24 2000-07-17 株式会社東芝 衝撃波治療装置及び温熱治療装置
IN172208B (de) 1990-04-02 1993-05-01 Sint Sa
EP0460536B1 (de) 1990-05-31 1994-10-12 Kabushiki Kaisha Toshiba Vorrichtung für Lithotripsie
US5394786A (en) 1990-06-19 1995-03-07 Suppression Systems Engineering Corp. Acoustic/shock wave attenuating assembly
US5055051A (en) 1990-08-03 1991-10-08 Dornier Medical Systems, Inc. Semi-anthropomorphic biliary/renal training phantom for medical imaging and lithotripsy training
NO912922L (no) 1990-09-05 1992-03-06 Atochem North America Peroksyder for polymeriseringsreaksjoner.
DE4032357C1 (de) 1990-10-12 1992-02-20 Dornier Medizintechnik Gmbh, 8000 Muenchen, De
DE4205030C2 (de) 1991-02-28 1997-04-03 Hitachi Ltd Therapeutische Ultraschallvorrichtung
US5289856A (en) 1991-03-04 1994-03-01 Amoco Corporation Multi-purpose nozzle with liquid pickup
EP0514010B1 (de) 1991-04-15 1996-02-07 Kabushiki Kaisha Toshiba Vorrichtung zum Zerstören von Konkrementen
DE4113697A1 (de) 1991-04-26 1992-11-05 Dornier Medizintechnik Vorrichtung zur fokalbereichsortung fuer die lithotripsie
DE4125950C1 (de) 1991-08-06 1992-11-05 Dornier Medizintechnik Gmbh, 8000 Muenchen, De
FR2680460B1 (fr) 1991-08-21 1999-08-20 Technomed Int Sa Procede et appareil de determination de la position exacte d'une cible a l'aide d'un dispositif de reception subdivise en une multiplicite d'elements discrets sensibles aux rayonnements.
DE4143540C2 (de) 1991-10-24 1996-08-08 Siemens Ag Therapieeinrichtung zur Behandlung eines Patienten mit fokussierten akustischen Wellen
US5524620A (en) 1991-11-12 1996-06-11 November Technologies Ltd. Ablation of blood thrombi by means of acoustic energy
WO1993022976A1 (en) 1992-05-12 1993-11-25 Delmenico Peter F Method and apparatus to establish target coordinates for lithotripsy
US5301659A (en) 1992-06-08 1994-04-12 Bantum Tripter Joint Venture Extracorporeal shockwave lithotripter
US5318014A (en) 1992-09-14 1994-06-07 Coraje, Inc. Ultrasonic ablation/dissolution transducer
US5362309A (en) 1992-09-14 1994-11-08 Coraje, Inc. Apparatus and method for enhanced intravascular phonophoresis including dissolution of intravascular blockage and concomitant inhibition of restenosis
US5658892A (en) * 1993-01-15 1997-08-19 The General Hospital Corporation Compound delivery using high-pressure impulse transients
DE4302537C1 (de) 1993-01-29 1994-04-28 Siemens Ag Therapiegerät zur Ortung und Behandlung einer Zone im Körper eines Lebewesens mit akustischen Wellen
US5650156A (en) 1993-02-22 1997-07-22 Vivorx Pharmaceuticals, Inc. Methods for in vivo delivery of nutriceuticals and compositions useful therefor
US5665382A (en) 1993-02-22 1997-09-09 Vivorx Pharmaceuticals, Inc. Methods for the preparation of pharmaceutically active agents for in vivo delivery
AU673057B2 (en) 1993-02-22 1996-10-24 Abraxis Bioscience, Llc Methods for (in vivo) delivery of biologics and compositionsuseful therefor
US5665383A (en) 1993-02-22 1997-09-09 Vivorx Pharmaceuticals, Inc. Methods for the preparation of immunostimulating agents for in vivo delivery
DE4309456A1 (de) 1993-03-24 1994-09-29 Hoechst Ag Polyethylenmassen zum Spritzgießen
DE4318237A1 (de) 1993-06-01 1994-12-08 Storz Medical Ag Vorrichtung zur Behandlung von biologischem Gewebe und Körperkonkrementen
US5395592A (en) 1993-10-04 1995-03-07 Bolleman; Brent Acoustic liquid processing device
DE9414692U1 (de) 1994-09-10 1994-11-03 Draegerwerk Ag Fahrgestell für ein medizinisches Gerät
DE4443495A1 (de) 1994-12-07 1996-06-20 Philips Patentverwaltung Lithotripsiekombination mit einer Therapieeinheit
DE4446192A1 (de) 1994-12-23 1996-07-04 Wolf Gmbh Richard Verfahren zur Trefferkontrolle
WO1996020784A1 (en) 1995-01-06 1996-07-11 Trustees Of Boston University Method and apparatus for enhancing chemical reactions through acoustic cavitation
DE19509004C1 (de) 1995-03-13 1996-10-24 Siemens Ag Akustisches Therapiegerät
US5572569A (en) 1995-03-31 1996-11-05 Beta Medical Products Tilting imaging table
US5795581A (en) 1995-03-31 1998-08-18 Sandia Corporation Controlled release of molecular components of dendrimer/bioactive complexes
US5642898A (en) 1995-07-11 1997-07-01 Wise; Robert W. Tool cart
US6245347B1 (en) 1995-07-28 2001-06-12 Zars, Inc. Methods and apparatus for improved administration of pharmaceutically active compounds
WO1999013943A1 (en) 1996-03-05 1999-03-25 Ekos Corporation Ultrasound assembly for use with light activated drugs
DE19622919C1 (de) 1996-06-07 1997-08-21 Dornier Medizintechnik Vorrichtung zur Ortung und Zertrümmerung von Konkrementen
DE19625164A1 (de) 1996-06-24 1998-01-02 Wolf Gmbh Richard Vorrichtung zum Auflösen von Thromben
DE19631246A1 (de) 1996-08-02 1998-02-05 Juergen Ziehm Fahrbares chirurgisches Röntgendiagnostikgerät
DE19702829A1 (de) 1997-01-27 1998-07-30 Siemens Ag Medizinisches Gerät
DE19709918C2 (de) 1997-03-11 2001-02-01 Dornier Medizintechnik Hochleistungs-Druckwellenquelle
US5864517A (en) 1997-03-21 1999-01-26 Adroit Systems, Inc. Pulsed combustion acoustic wave generator
DE19718511C5 (de) 1997-05-02 2010-10-21 Sanuwave, Inc., Gerät zur Applikation von akustischen Stoßwellen
US6416740B1 (en) 1997-05-13 2002-07-09 Bristol-Myers Squibb Medical Imaging, Inc. Acoustically active drug delivery systems
US6276471B1 (en) 1997-06-06 2001-08-21 EXPRESSO DEUTSCHLAND TRANSPOTGERäTE GMBH Delivery cart
US6036611A (en) 1997-07-07 2000-03-14 Poclain Hydraulics Industrie Drive mechanism for driving displacement members disposed in tandem
DE29712035U1 (de) 1997-07-09 1997-09-11 Dornier Medizintechnik Therapievorrichtung
US6231516B1 (en) 1997-10-14 2001-05-15 Vacusense, Inc. Endoluminal implant with therapeutic and diagnostic capability
US6585763B1 (en) 1997-10-14 2003-07-01 Vascusense, Inc. Implantable therapeutic device and method
DE19746956C2 (de) 1997-10-23 2000-05-11 Siemens Ag Medizinisches System aufweisend ein Röntgengerät und ein Therapiegerät mit einer Quelle fokussierter akustischer Wellen
US6066123A (en) * 1998-04-09 2000-05-23 The Board Of Trustees Of The Leland Stanford Junior University Enhancement of bioavailability by use of focused energy delivery to a target tissue
CA2238951A1 (fr) 1998-05-26 1999-11-26 Les Technologies Sonomax Inc. Reacteur a cavitation acoustique pour le traitement des materiaux
JP2002520298A (ja) 1998-07-13 2002-07-09 ザ・ボード・オブ・リージェンツ・オブ・ザ・ユニバーシティー・オブ・ネブラスカ 標的化部位特異的薬物送達組成物および使用方法
US6298264B1 (en) 1998-08-31 2001-10-02 Duke University Apparatus and method for macromolecule delivery into living cells
DE19843680C1 (de) 1998-09-23 2000-02-24 Dornier Medtech Holding Int Gmbh Urologischer Arbeitsplatz mit einer Röntgenstrahlungsquelle- und Strahlungsempfänger-Anordnung
US6135357A (en) 1998-11-23 2000-10-24 General Electric Company Apparatus for atomizing high-viscosity fluids
US6296619B1 (en) 1998-12-30 2001-10-02 Pharmasonics, Inc. Therapeutic ultrasonic catheter for delivering a uniform energy dose
US6428532B1 (en) 1998-12-30 2002-08-06 The General Hospital Corporation Selective tissue targeting by difference frequency of two wavelengths
US6444192B1 (en) 1999-02-05 2002-09-03 The Regents Of The University Of California Diagnostic imaging of lymph structures
US7107997B1 (en) 1999-03-16 2006-09-19 Jeffrey Warren Moses Method and apparatus for increasing angiogenic, growth factor in heart muscle
US6206835B1 (en) 1999-03-24 2001-03-27 The B. F. Goodrich Company Remotely interrogated diagnostic implant device with electrically passive sensor
US6424863B1 (en) 1999-03-26 2002-07-23 Stephen T. Flock Delivery of pharmaceutical compounds and collection of biomolecules using electromagnetic energy and uses thereof
AU5154000A (en) 1999-05-19 2000-12-05 Brigham Young University Stabilization and acoustic activation of polymeric micelles for drug delivery
CA2377866A1 (en) 1999-06-14 2000-12-21 Roger J. Talish Method and kit for cavitation-induced tissue healing with low intensity ultrasound
US6709427B1 (en) * 1999-08-05 2004-03-23 Kensey Nash Corporation Systems and methods for delivering agents into targeted tissue of a living being
EP1244770A2 (de) 1999-12-23 2002-10-02 Dornier Medizintechnik GmbH Vorrichtung zum transfer von molekülen in zellen
US6496557B2 (en) 2000-02-09 2002-12-17 Hologic, Inc. Two-dimensional slot x-ray bone densitometry, radiography and tomography
US6386560B2 (en) 2000-04-25 2002-05-14 Joseph P. Calender Dolly for large appliances
US6444217B1 (en) 2000-04-25 2002-09-03 University Of Washington Drug delivery devices, and methods of use
US6875176B2 (en) 2000-11-28 2005-04-05 Aller Physionix Limited Systems and methods for making noninvasive physiological assessments
DE10062749C1 (de) 2000-12-15 2002-04-04 Dornier Medtech Holding Int Gmbh Koppelbalg zur Stoßwellentherapie
US6986764B2 (en) 2000-12-15 2006-01-17 Laserscope Method and system for photoselective vaporization of the prostate, and other tissue
SE0100758D0 (sv) 2001-03-07 2001-03-07 Siemens Elema Ab Vagn och kärra
DE10111800A1 (de) 2001-03-12 2002-10-02 Siemens Ag Mobiles medizintechnisches Gerät und Verwendung einer elektromechanischen Feststellbremse für ein derartiges medizintechnisches Gerät
US6478741B2 (en) 2001-03-19 2002-11-12 General Electric Company Transmission of optimized pulse waveforms for ultrasonic subharmonic imaging
US7311731B2 (en) * 2001-04-27 2007-12-25 Richard C. Satterfield Prevention of myocardial infarction induced ventricular expansion and remodeling
AU2002321804A1 (en) * 2001-08-01 2003-02-17 Nvr Lab Inc. Method for selective enhancement of cell growth
DE10145852B4 (de) 2001-09-17 2005-08-25 Richard Wolf Gmbh Medizinische Vorrichtung
DE10158519B4 (de) 2001-11-29 2005-01-13 Dornier Medtech Holding International Gmbh Stoß- und Druckwellen-Therapiegerät
DE10162595A1 (de) 2001-12-19 2003-07-10 Dornier Medtech Holding Int Gmbh Prüfung und Überwachung einer Stoss- bzw. Druckwellenquelle
KR20040086503A (ko) 2002-01-28 2004-10-11 마츠시타 덴끼 산교 가부시키가이샤 음향 정합층, 초음파 송수파기 및 초음파 유량계
DE10206193C1 (de) 2002-02-14 2003-07-03 Siemens Ag Vorrichtung und Verfahren zur Ausrichtung eines Röntgengerätes und eines Therapiegerätes relativ zueinander
DE10234144A1 (de) 2002-07-26 2004-02-05 Dornier Medtech Gmbh Lithotripter
DE20315924U1 (de) 2003-10-17 2005-02-24 Dornier Medtech Systems Gmbh Therapiekopf eines Lithotripters und Lithotripter
DE102005037043C5 (de) 2005-08-05 2017-12-14 Dornier Medtech Systems Gmbh Stoßwellentherapiegerät mit Bildgewinnung
DE102006037289B4 (de) 2006-08-09 2008-08-07 Limmer Laser Gmbh Vorrichtung zur Vaporisation von Gewebe mittels Laserstrahlung

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2707391A (en) * 1951-10-23 1955-05-03 Bell Telephone Labor Inc Testing viscous liquids
US3934458A (en) * 1974-02-04 1976-01-27 Technicon Instruments Corporation Method and apparatus for pulse echo imaging
US4240285A (en) * 1978-08-09 1980-12-23 The Marconi Company Limited Measurement of the density of liquids
US4712037A (en) * 1985-07-03 1987-12-08 Nederlandse Centrale Organisatie Voor Toegepast-Natuurwetenschappelijk Onderzoek Resonant piezoelectric sensor
US6039565A (en) * 1997-01-14 2000-03-21 Chou; Marilyn M. Combined ultrasonic and laser device and method of use

Cited By (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7988648B2 (en) 2005-03-04 2011-08-02 General Patent, Llc Pancreas regeneration treatment for diabetics using extracorporeal acoustic shock waves
US20070142753A1 (en) * 2005-03-04 2007-06-21 General Patent Llc Pancreas regeneration treatment for diabetics using extracorporeal acoustic shock waves
US8500623B2 (en) 2006-11-30 2013-08-06 Miracor Medical Systems Gmbh Method and device for intermittent occlusion of a vein draining the organ system
US8162813B2 (en) * 2006-11-30 2012-04-24 Miracor Medical Systems Gmbh Method and device for the intermittent occlusion of a vein draining the organ system
US20100056849A1 (en) * 2006-11-30 2010-03-04 Miracor Medical Systems Gmbh Method and device for the intermittent occlusion of a vein draining the organ system
US8996106B2 (en) 2006-11-30 2015-03-31 Miracor Medical Systems Gmbh Method and device for intermittent occlusion of a vein draining the organ system
US20110034832A1 (en) * 2009-07-08 2011-02-10 Iulian Cioanta Usage of Extracorporeal and Intracorporeal Pressure Shock Waves in Medicine
US11925366B2 (en) 2009-07-08 2024-03-12 Sanuwave, Inc. Catheter with multiple shock wave generators
US8556813B2 (en) 2009-07-08 2013-10-15 Sanuwave, Inc. Extracorporeal pressure shock wave device
US11666348B2 (en) 2009-07-08 2023-06-06 Sanuwave, Inc. Intracorporeal expandable shock wave reflector
US10639051B2 (en) 2009-07-08 2020-05-05 Sanuwave, Inc. Occlusion and clot treatment with intracorporeal pressure shock waves
US10058340B2 (en) 2009-07-08 2018-08-28 Sanuwave, Inc. Extracorporeal pressure shock wave devices with multiple reflectors and methods for using these devices
US10238405B2 (en) 2009-07-08 2019-03-26 Sanuwave, Inc. Blood vessel treatment with intracorporeal pressure shock waves
US10583069B2 (en) * 2012-01-27 2020-03-10 Avner Spector Method for improving kidney function with extracorporeal shockwaves
US20130197404A1 (en) * 2012-01-27 2013-08-01 Avner Spector Method for imporoving kidney function with extracorporeal shockwaves
US20210153885A1 (en) * 2012-01-27 2021-05-27 Avner Spector Method of treatment with low energy extracorporeal shockwaves
US11771447B2 (en) * 2012-01-27 2023-10-03 Avner Spector Method of treatment with low energy extracorporeal shockwaves
US11517499B2 (en) * 2012-01-27 2022-12-06 Avner Spector Method for improving kidney function with extracorporeal shockwaves
US10561425B2 (en) 2013-12-11 2020-02-18 Miracor Medical Sa System and method for treating heart tissue
US9855049B2 (en) 2013-12-11 2018-01-02 Miracor Medical Systems Gmbh System and method for treating heart tissue
US11607225B2 (en) 2013-12-11 2023-03-21 Miracor Medical Sa System and method for treating heart tissue
US11389370B2 (en) * 2016-04-18 2022-07-19 Softwave Tissue Regeneration Technologies, Llc Treatments for blood sugar levels and muscle tissue optimization using extracorporeal acoustic shock waves
US11389372B2 (en) 2016-04-18 2022-07-19 Softwave Tissue Regeneration Technologies, Llc Acoustic shock wave therapeutic methods
US11458069B2 (en) 2016-04-18 2022-10-04 Softwave Tissue Regeneration Technologies, Llc Acoustic shock wave therapeutic methods to treat medical conditions using reflexology zones
US11389373B2 (en) 2016-04-18 2022-07-19 Softwave Tissue Regeneration Technologies, Llc Acoustic shock wave therapeutic methods to prevent or treat opioid addiction
US20170296427A1 (en) * 2016-04-18 2017-10-19 General Patent, Llc Treatments for blood sugar levels and muscle tissue optimization using extracorporeal acoustic shock waves
US20220031563A1 (en) * 2016-04-18 2022-02-03 Softwave Tissue Regeneration Technologies, Llc Treatments for blood sugar levels and muscle tissue optimization using extracorporeal acoustic shock waves
US11389371B2 (en) 2018-05-21 2022-07-19 Softwave Tissue Regeneration Technologies, Llc Acoustic shock wave therapeutic methods
US11826301B2 (en) 2018-05-21 2023-11-28 Softwave Tissue Regeneration Technologies, Llc Acoustic shock wave therapeutic methods
US20200269073A1 (en) * 2019-02-22 2020-08-27 Creative Medical Technologies, Inc. Extracorporeal shock wave ultrasound for enhancement of regenerative activities in erectile dysfunction

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US20080267927A1 (en) 2008-10-30
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