WO2015006510A1 - Procédés de traitement d'un infarctus du myocarde établi - Google Patents

Procédés de traitement d'un infarctus du myocarde établi Download PDF

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WO2015006510A1
WO2015006510A1 PCT/US2014/046052 US2014046052W WO2015006510A1 WO 2015006510 A1 WO2015006510 A1 WO 2015006510A1 US 2014046052 W US2014046052 W US 2014046052W WO 2015006510 A1 WO2015006510 A1 WO 2015006510A1
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construct
myocardial infarction
svf
stromal vascular
vascular fraction
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Stuart K. Williams
James Beatty Hoying
Amanda J. LEBLANC
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The University Of Louisville Research Foundation
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    • 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
    • A61K35/35—Fat tissue; Adipocytes; Stromal cells; Connective tissues
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A61L27/3804—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
    • A—HUMAN NECESSITIES
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    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56—Porous materials, e.g. foams or sponges
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
    • C12N5/0662—Stem cells
    • C12N5/0667—Adipose-derived stem cells [ADSC]; Adipose stromal stem cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
    • C12N5/0662—Stem cells
    • C12N5/0668—Mesenchymal stem cells from other natural sources
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents
    • A61L2300/414—Growth factors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/20—Materials or treatment for tissue regeneration for reconstruction of the heart, e.g. heart valves
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2533/00—Supports or coatings for cell culture, characterised by material
    • C12N2533/30—Synthetic polymers
    • C12N2533/40—Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers

Definitions

  • the presently-disclosed subject matter relates to methods for treating an established myocardial infarction.
  • the presently-disclosed subject matter relates to methods for treating an established myocardial infarction whereby a stromal vascular fraction construct is applied to the site of an established myocardial infarction in a subject.
  • Cardiac disease including coronary heart disease (CHD) and associated heart failure following myocardial infarction (MI) comprises the most direct and indirect costs of major cardiovascular diseases [1]. Since the innate ability of the heart to repair itself following a MI is largely limited, regenerative therapies for patients with acute MI are being investigated as a means to reduce the extent of ischemic damage, whether as a novel treatment or a supplement to current therapies, such as primary percutaneous coronary intervention and thrombolytic therapy [2] ⁇
  • LateTIME (NCT00684060) trials have recently been conducted to help determine the appropriate timing of cell-based therapy to improve ventricular function and structure post-MI [3]. Specifically, the LateTIME trial was to evaluate the efficacy of cell treatment 2-3 weeks following initial MI in an effort to address high-risk patients with persistent LV dysfunction [3]. This has prompted the need to evaluate the efficacy of successful acute MI cellular therapies in a more clinically challenging model of established or chronic ventricular dysfunction.
  • adipose tissue houses an easily isolatable, regenerative, and multipotent cell population defined as the stromal vascular fraction (SVF), consisting of endothelial cells, smooth muscle cells, blood cells and mesenchymal cells containing perivascular and adventitial cells [4,5].
  • SVF stromal vascular fraction
  • the broad clinical potential of SVF has significantly boosted the number of ongoing clinical trials utilizing adipose-derived cells as a cell therapy [6]. It is worth noting, though, most cell-based therapies are limited by the lack of retention of cells into the target tissue.
  • the above method increases the amount of perfused vessels at the site of the established myocardial infarction.
  • FIG. 1A is a plot representing single PV loop recordings during baseline. All MI hearts display a rightward shift in PV relationship compared to the representative control PV loop.
  • FIG. IB is a table summarizing cardiac functional parameters during PV loop recordings and respective ANOVA p-values. Emax was significantly higher for MI SVF than either the MI or MI Vicryl groups. The asterisk ⁇ *) indicates significantly different than MI SVF.
  • FIG. 1C is a set of graphs showing representative PV loops obtained at different preloads, showing differences in the end-systolic PV relationship (ESPVR, or Emax) between MI (left), MI SVF (center) and MI Vicryl (right). The less steep Emax in the MI and MI Vicryl loops indicate decreased systolic performance.
  • ESPVR end-systolic PV relationship
  • FIG. 2 A is an 18 F-FDG PET scan showing an uptake defect in partitioned polar maps in all groups [anterior (top), lateral (right), apex (center)].
  • FIG. 2B is a chart showing that relative infarcted volume, calculated as a ratio of infarcted volume (regions with 18 F-FDG uptake ⁇ 70%) to total LV volume, was significantly higher in the MI and MI Vicryl groups compared to MI SVF.
  • FIG. 3 A is set of representative photographs of explanted hearts.
  • FIG. 3C is a chart showing infarct size as a percentage of total LV per experimental group by trichrome analysis.
  • FIG. 4B is a chart showing how the example MI SVF group exhibited significantly more GS-1+ vessels in the area of infarct when compared to both the MI and MI Vicryl groups.
  • FIG. 5B is a chart showing the percentage of perfused vessels in this example.
  • FIG. 6A-G show cumulative data comparing MI SVF with the time point of intervention, MI 2wk. On several parameters, MI SVF hearts maintain similar cardiac function and vascular dynamics as the MI 2wk group.
  • FIG. 6 A is a plot of representative PV loops showing both the lack of rightward shift (vs. MI 2wk) or reversal of dysfunction (vs. control) for MI SVF.
  • FIG. 6B is a table containing a summary of cardiac functional parameters as assessed by PV loops.
  • FIG. 6C is a set of two 18 F-FDG uptake PET polar map views.
  • FIG. 6D is a chart showing percent relative infarct volume from PET data.
  • FIG. 6F is a chart showing that MI SVF had significantly higher count of GS-1+ vessel density in the area of infarct than MI 2wk.
  • FIG. 6G is a chart displaying percent perfused vessels in the area of infarct.
  • the term "about,” when referring to a value or to an amount of mass, weight, time, volume, concentration or percentage is meant to encompass variations of in some embodiments ⁇ 20%, in some embodiments ⁇ 10%, in some embodiments ⁇ 5%, in some embodiments ⁇ 1%, in some embodiments ⁇ 0.5%, and in some embodiments ⁇ 0.1% from the specified amount, as such variations are appropriate to perform the disclosed method.
  • ranges can be expressed as from “about” one particular value, and/or to “about” another particular value. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as “about” that particular value in addition to the value itself. For example, if the value “10” is disclosed, then “about 10” is also disclosed. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.
  • a stromal vascular fraction (SVF) construct after a myocardial infarction (MI) and onto an established MI or, in other words, onto a MI during the weeks to months following a MI where cellular necrosis, the beginning of scar tissue formation, and thinning of outer LV wall occurs
  • MI myocardial infarction
  • the cell-based intervention provided by applying the SVF construct onto an established infarct halts further deterioration of left ventricular (LV) function compared to untreated hearts, and that this is accomplished, at least in part, through an increase in coronary neovascularization and perfusion, as well as a retention of implanted regenerative cells in the area of infarct.
  • the presently- disclosed subject matter thus includes methods for treating an established myocardial infarction and, in particular, methods for treating an established myocardial infarction whereby a stromal vascular fraction construct is applied to the site of an established myocardial infarction in a subject.
  • a method of treating an established myocardial infarction comprises the steps of: providing a stromal vascular fraction construct, the stromal vascular fraction construct including an amount of stromal vascular fraction cells seeded onto a biocompatible substrate; and applying the stromal vascular fraction construct to the site of the established myocardial infarction in a subject.
  • the stromal vascular fraction construct can be applied to the site of the established myocardial infarction at a time period of about 2 weeks to about 6 weeks following a myocardial infarction in the subject to thereby treat the established myocardial infarction.
  • applying the stromal vascular fraction construct to the site of the established myocardial infarction comprises suturing the stromal vascular fraction construct to an epicardial surface of the heart of the subject.
  • treatment relate to any treatment of an established myocardial infarction, including but not limited to prophylactic treatment and therapeutic treatment.
  • treatment or “treating” include, but are not limited to: preventing an established myocardial infarction or the development of an established myocardial infarction; inhibiting the progression of an established myocardial infarction;
  • applying the stromal vascular fraction construct decreases an amount of fibrosis at the site of the established myocardial infarction. In some embodiments, applying the stromal vascular fraction construct increases an amount of perfused vessels at the site of the established myocardial infarction. In further embodiments, applying the stromal vascular fraction construct reduces an amount of myocardial cell death at the site of the established myocardial infarction.
  • applying the stromal vascular fraction construct increases an amount of growth factors at the site of the established myocardial infarction.
  • the growth factors are selected from the group consisting of vascular endothelial growth factor, transforming growth factor-beta 1 , placental growth factor, and basic fibroblast growth factor.
  • the growth factor is vascular endothelial growth factor (VEGF).
  • the stromal vascular fraction used in the constructs are those that are typically obtained by enzymatically digesting an amount of adipose tissue obtained from a subject, followed by a period of centrifugation to pellet the stromal vascular fraction of the adipose tissue.
  • the stromal vascular fraction contains a number of cell types, including preadipocytes, mesenchymal stem cells (MSCs), endothelial progenitor cells, T cells, B cells, mast cells, and adipose tissue macrophages, as well as small blood vessels or microvascular fragments found within the stromal vascular fraction.
  • the substrates used in connection with the stromal vascular fraction construct can be comprised of a number of materials, but are generally comprised of biocompatible materials that will not have a long-lasting inflammatory or other adverse effects when placed in the body of a subject.
  • the biocompatible substrate comprises a vicryl mesh.
  • the term "subject” includes both human and animal subjects.
  • veterinary therapeutic uses are provided in accordance with the presently disclosed subject matter.
  • the presently-disclosed subject matter provides for the treatment of mammals such as humans, as well as those mammals of importance due to being endangered, such as Siberian tigers; of economic importance, such as animals raised on farms for consumption by humans; and/or animals of social importance to humans, such as animals kept as pets or in zoos. Examples of such animals include but are not limited to: carnivores such as cats and dogs;
  • swine including pigs, hogs, and wild boars
  • ruminants and/or ungulates such as cattle, oxen, sheep, giraffes, deer, goats, bison, and camels
  • horses Also provided is the treatment of birds, including the treatment of those kinds of birds that are endangered and/or kept in zoos, as well as fowl, and more particularly domesticated fowl, i.e., poultry, such as turkeys, chickens, ducks, geese, guinea fowl, and the like, as they are also of economic importance to humans.
  • livestock including, but not limited to, domesticated swine, ruminants, ungulates, horses (including race horses), poultry, and the like.
  • Buoyant adipocytes were removed by centrifugation and the entire cell pellet suspended in 0.1% BSA-PBS. Cells were immediately plated (l x lO 6 cells/cm 2 ) onto a piece of VicrylTM 1 x 1.5 cm, and cultured for 14 days in Dulbecco's Modified Eagle's Medium (DMEM) with 10% FBS.
  • DMEM Dulbecco's Modified Eagle's Medium
  • the MI 2wk group was included to compare the SVF treated group to the time point of intervention.
  • the Vicryl alone implant group was included as an epicardial implant control. All endpoint parameters were assessed at 2 weeks or 6 weeks following initial MI. Rats were euthanized by removal of the heart.
  • IVC inferior vena cava
  • An apical stab was used for catheter insertion, and the catheter was positioned along the cardiac longitudinal axis with the distal electrode in the aortic root and the proximal electrode in the LV apex. Placement of the catheter was monitored directly.
  • Overall LV function was assessed under baseline conditions, following transient inferior vena cava (IVC) occlusion (to assess contractility and LV stiffness), and after intravenous administration of 20-40 ul of 30% saline (for conductance volume calibration).
  • IVC transient inferior vena cava
  • the most widely used and validated PET radiotracer for the assessment of myocardial glucose utilization and metabolically active tissue is 18 F-FDG [13].
  • Each rat was injected with a dose of 18 F-FDG (28-44 MBq x 0.6 ml saline) via the lateral tail veins.
  • 18 F-FDG IV injection each rat was anesthetized with isoflurane (1-3%) and securely taped onto the imaging bed of a Siemens R4 MicroPET (Knoxville, TN).
  • Siemens R4 MicroPET Knoxville, TN
  • a 17-partitioned polar cardiac map was produced for each rat. Imaging data was analyzed with the Siemens Inveon Imaging system.
  • Reduced uptake regions ( ⁇ 70% of the maximum uptake) were calculated by summing the individual volumes (in mm 3 ) from each reduced 18 F-FDG uptake region.
  • Total left ventricle (LV) volume was calculated by summing the individual volumes from all short axis slices. The extension of infarction was compared between animals using the equation:
  • % Relative Infarcted Volume (Infarcted myocardial volume / Total LV volume) x 100
  • Rats received an injection of anesthesia (Ketamine 40-80 mg/kg and Xylazine 5-10 mg/kg) and then were perfused with dextran (Tetramethylrhodamine, Molecular Probes) at 2 mg/ml via the jugular vein (circulating 15') before hearts were explanted.
  • dextran Tetramethylrhodamine, Molecular Probes
  • 18 F-FDG PET is considered the most sensitive means to assess myocardial viability compared to any other imaging modality [16].
  • Myocardial glucose utilization (indicative of metabolism) measured by 18 F-FDG uptake demonstrated the ischemic injury in the anterior wall of infarcted rats in the representative polar maps (FIG. 2A).
  • percent relative infarcted volume was calculated in each group. Percent relative infarcted volume was significantly increased in MI and MI Vicryl compared to MI SVF hearts (MI: 12.9 ⁇ 0.7, MI Vicryl: 12.6 ⁇ 0.7, MI SVF: 9.1 ⁇ 0.9, FIG. 2B).
  • Example 3 Heart remodeling and fibrosis following post-MI intervention.
  • Example 4 Vessel Characteristics in the Area of Infarct.
  • Example 5 SVF Construct and Time Point of Intervention.
  • Example 7 Vascular endothelial growth factor (VEGF) production.
  • VEGF vascular endothelial growth factor
  • the above examples illustrate, among other things, that regenerative medicine therapy previously shown to preserve myocardial function following MI can restore and/or maintain function if applied at a later time point.
  • the primary findings from this study are: 1) clinical indices of heart function, such as Emax (indicative of systolic performance and contractile function) and PET imaging of cardiac viability, established that treatment with the SVF construct at 2 weeks post-MI halted the progressive worsening of LV function displayed by untreated and control MI hearts (MI and MI Vicryl), and 2) hearts treated with an SVF construct exhibited an increase in both total and perfused vessels in the infarcted area compared to MI and MI Vicryl.
  • Emax indicative of systolic performance and contractile function
  • PET imaging of cardiac viability established that treatment with the SVF construct at 2 weeks post-MI halted the progressive worsening of LV function displayed by untreated and control MI hearts (MI and MI Vicryl), and 2) hearts treated with an SVF construct exhibited an increase in both total and
  • a major barrier to the efficacy of regenerative medicine in a given tissue is the method of delivery of the selected cell population.
  • the volume of cells that remain in the heart, delivered either by direct injection into the myocardium or through intracoronary infusion, can be ⁇ 10% hours after transplantation [7,17].
  • Catheter-based injectable materials offer an alternative solution to delivering cells directly to the infarcted area while simultaneously facing the need for a longer-lasting cell-matrix platform and interaction within the myocardium;
  • Adipose-derived micro vessels [22] and cells [23] have the capability of forming a de novo microvasculature and migrating into the vessel wall of existing neovessel segments to assemble parts of the vasculature; however, this study suggests a likelier mechanism where implantation of the SVF construct following MI promotes a positive neovascularizing environment.
  • VEGF vascular endothelial growth factor
  • VEGF vascular endothelial growth factor
  • adipose-derived stem cells can also produce large amounts of transforming growth factor Pi(TGFPi), placental growth factor, and basic fibroblast growth (FGF) factor [27], all of which support the impressive angiogenic effects reported previously [10,27,28].
  • Culturing cells on a 3D construct may alter the relative expression and production of these growth factors and cytokines secreted by SVF, but this is unlikely in our hands.
  • PET imaging is a well-established modality to evaluate myocardial perfusion, metabolism and viability in the clinical population, it is used significantly less in rodent models of MI [29].
  • 18 F-FDG is considered the most sensitive means to assess myocardial viability.
  • the uptake of glucose by the myocardium is increased acutely, but is decreased in areas of very severe ischemia.
  • Clinical trials using bone marrow-derived stem cell (BMSC) intracoronary injection therapy for both acute [30,31] and chronic [32] MI have shown an increased 18 F-FDG uptake in the infarct zone of patients.
  • BMSC bone marrow-derived stem cell
  • Auspicious microcirculatory function is a critical factor in the post-MI repair process and is linked with increased viable myocardium following acute MI [34,35].
  • the current results support this association, as MI SVF hearts exhibited preserved myocardial viability (FIG. 2) and increased vessel count and perfusion in the at-risk area compared to MI and MI Vicryl hearts (FIG. 4,FIG. 5).
  • Multiple studies have shown a similar increase in vessel density (through IHC) in chronic MI hearts after treatment with either BMSC [36] or ADSC [37,38].
  • BMSC through IHC
  • Therapeutic treatment with the SVF construct on an established infarct may result in preserved myocardial viability and function, in addition to increased microvascular perfusion in the infarcted area compared to untreated MI hearts in rats.
  • This tissue engineering approach of creating an SVF-laden construct can increase the cell quantity that can be implanted into an ischemic area without massive rates of acute cell death and also improves cell retention over time [18].
  • the present results indicate that treatment with an SVF construct, either immediately or during the active remodeling phase of scar formation post-MI, halts deteriorating cardiac function and maintains LV viability and microcirculatory perfusion.
  • the clinical potential of an autologous construct made from adipose-derived SVF is high, as the SVF construct may be utilized in conjunction to existing MI therapies to promote microvessel survival and/or growth of new vessels following coronary infarct.
  • Camici PG Camici PG, Prasad SK, Rimoldi OE. stunning, Hibernation, and Assessment of
  • Pacher P Mabley JG, Liaudet L, et al. Left Ventricular Pressure- Volume Relationship in a Rat Model of Advanced Aging- Associated Heart Failure. Am J Physiol Heart Circ Physiol. 2004;287:H2132-2137.

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Abstract

L'invention concerne des procédés de traitement d'un infarctus du myocarde établi, comprenant un traitement au moyen d'une construction épicardique contenant une fraction stroma-vasculaire (FSV) provenant de tissu adipeux qui peut être semée sur un substrat biocompatible, ce qui préserve la fonction micro-vasculaire et les mécanismes de contraction du ventricule gauche.
PCT/US2014/046052 2013-07-09 2014-07-09 Procédés de traitement d'un infarctus du myocarde établi WO2015006510A1 (fr)

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WO2021003340A1 (fr) * 2019-07-03 2021-01-07 United States Government As Represented By The Department Of Veterans Affairs Compositions et méthodes de traitement du myocarde à l'aide d'un échafaudage de cellules souches mésenchymateuses

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US20120201890A1 (en) * 2009-10-13 2012-08-09 University Of Louisville Research Foundation, Inc. Methods and compositions to support transplanted tissue integration and innosculation with adipose stromal cells
WO2013049862A1 (fr) * 2011-09-30 2013-04-04 University Of Louisville Research Foundation, Inc. Construction à base de cellules de la fraction stroma-vasculaire du tissu adipeux soutenant la fonction microvasculaire coronarienne après un infarctus du myocarde aigu

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