WO2010063887A1 - Régénérat biologique pour utilisation en oblitération - Google Patents

Régénérat biologique pour utilisation en oblitération Download PDF

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WO2010063887A1
WO2010063887A1 PCT/FI2009/050967 FI2009050967W WO2010063887A1 WO 2010063887 A1 WO2010063887 A1 WO 2010063887A1 FI 2009050967 W FI2009050967 W FI 2009050967W WO 2010063887 A1 WO2010063887 A1 WO 2010063887A1
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Prior art keywords
stem cells
biological
composition
regenerate
obliteration
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PCT/FI2009/050967
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English (en)
Inventor
Jura Numminen
Bettina Lindroos
Marjo-Riitta Suuronen
Susanna Miettinen
Markus Rautiainen
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Tampereen Yliopisto, Solu- Ja Kudosteknologiakeskus Regea
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Publication of WO2010063887A1 publication Critical patent/WO2010063887A1/fr

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    • 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
    • A61L27/3834—Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem 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
    • A61K38/1875—Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
    • 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
    • A61L27/02—Inorganic materials
    • A61L27/10—Ceramics or glasses
    • 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
    • A61L27/3839—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 the site of application in the body
    • 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
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • 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
    • 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
    • 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
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • A61L2300/406—Antibiotics
    • 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
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • A61L2300/408—Virucides, spermicides
    • 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
    • A61L2300/41—Anti-inflammatory agents, e.g. NSAIDs
    • 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
    • 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
    • A61L2300/428—Vitamins, e.g. tocopherol, riboflavin
    • 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
    • A61L2300/43—Hormones, e.g. dexamethasone
    • 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
    • C12N2533/00—Supports or coatings for cell culture, characterised by material
    • C12N2533/10—Mineral substrates
    • C12N2533/12—Glass
    • 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
    • C12N2533/00—Supports or coatings for cell culture, characterised by material
    • C12N2533/10—Mineral substrates
    • C12N2533/14—Ceramic

Definitions

  • the invention relates to a composition and a to biological regenerate comprising mesenchymal stem cells and an osteoinductive material for use in frontal sinus obliteration, and particularly in treating chronic frontal sinusitis.
  • Frontal sinus obliteration is a surgical technique that has been used clinically for decades to treat chronically infected sinuses.
  • the pathological sinus mucosa and the inner cortical bony lining are removed surgically and the sinuses are filled with a suitable material.
  • Different obliteration materials have been used during the last decades, and the success rates often depend on the choice of these materials.
  • One of the most commonly used materials is abdominal fat.
  • problems such as re- aeration and abdominal donor site morbidity have been frequently seen in a long term follow-up (Schenck, Laryngoscope 1975;85:76-92).
  • Suitable and widely used obliteration materials include synthetic materials such as tricalcium phosphate and hydroxyapatite bone cements, (DAddario et al., J Long-Term Effects of Med lmpl 2004;14(6):455- 465).
  • synthetic materials eliminates the disadvantage of donor site morbidity.
  • the results obtained with hydroxyapatite are often unsatisfactory and the long-term outcome is quite poor.
  • the use of hydroxyapatite may involve rejections and postoperative infections. Another problem is that hydroxyapatite cannot be used directly adjacent to dura.
  • bioactive glass granules have been the best choice for obliteration.
  • the advantages of bioactive glass include easy handling, osteoconductivity, and nontoxicity.
  • transformation of bioactive glass into bone requires a long time, which raises the risk of late complications, such as relapse of the infection.
  • Still another object of the present invention is to provide a method of treating frontal sinusitis by obliteration.
  • the method comprises administering into a frontal sinus of a patient in need of such treatment a biological regenerate comprising a composition of mesenchymal stem cells and at least one osteoinductive biocompatible material.
  • the mesenchymal stem cells are derived from adipose tissue.
  • the osteoinductive material is selected from a group consisting of bioactive glasses and glass ceramics.
  • a suitable bioactive glass contains about 45% SiO 2 , about 24.5%
  • the bioactive glass contains about 53% SiO 2 , about 23% Na 2 O, about 20% CaO, and about 4% P 2 O 5 by weight of the composition.
  • Figure 1 shows a frontal CT scan of patient 1 before obliteration
  • Figure 2 shows a horizontal CT scan of patient 1 before the obliteration (frontal sinus within a circle);
  • Figure 3 shows a frontal CT scan of patient 1 one month after the obliteration
  • Figure 4 shows a horizontal CT scan of patient 1 one month after the obliteration (frontal sinus within a circle);
  • Figure 5 shows a frontal CT scan of patient 2 before obliteration
  • Figure 6 shows a horizontal CT scan of patient 2 before the obliteration (frontal sinus within a circle)
  • Figure 7 shows a frontal CT scan of patient 2 one month after the obliteration
  • Figure 8 shows a horizontal CT scan of patient 2 one month after the obliteration (frontal sinus within a circle).
  • the present invention relates to a composition and a biological regenerate comprising mesenchymal stem cells and a biocompatible osteoinductive material for use in frontal sinus obliteration, especially in treating chronic frontal sinusitis.
  • a biological regenerate it is meant herein a living implant or transplant that may be used to replace autogenic or allogenic body parts. More specifically, a biological regenerate is a biological composition which induces osteogenesis or bone formation, and may thus be used for obliteration purposes.
  • mesenchymal stem cells refer to multipotent adult stem cells, which are capable of differentiating into a variety of cell types, especially osteoblasts.
  • mesenchymal stem cells may be obtained from various autogenic or allogenic sources including, but not limited to, adipose tissue and bone marrow. Methods of isolating mesenchymal stem cells are known and are readily available.
  • autogenic stem cells from adipose tissue are an attractive source of cells for use in the present invention, owing for instance to the fact that they can be obtained in large quantities and they reduce the risk of immune rejection by the host and of transfer of infectious agents.
  • any biocompatible material that induces osteogenesis of mesenchymal stem cells may be used.
  • a biocompatible material refers to a safe and non-toxic material which does not elicit any undesirable local or systemic effects in the host.
  • an osteoinductive material refers to any material that is able to induce osteogenesis, i.e. bone formation, of mesenchymal stem cells. Osteogenic differentiation may be determined easily e.g. by histochemical alkaline phosphatase staining, as is well known in the art.
  • Biomaterials are synthetic or natural products that may be used in contact with tissues, blood or body fluids. They may be used for therapeutic, prosthetic and diagnostic purposes, yet the material does not harm a living biological organism. Synthetic materials can be divided into four classes; metals, ceramics, polymers, and composites (e.g. material combinations).
  • Natural biomaterials can be extracted from plants and animals or they can be produced by micro-organisms.
  • Suitable osteoinductive materials for use in the present invention include bioactive glasses and glass ceramics.
  • Bioactive glass is a well known bone substitute material as it is biocompatible, osteoconductive, provokes no significant inflammatory response, and is biodegradable.
  • bioactive glasses form a thin layer of calcium phosphate on their surfaces. In vivo and in vitro studies have demonstrated that the development of this bioactive layer stimulates the adjacent structures to form new bone.
  • One example of a suitable bioactive glass contains 45.0% SiO 2 ; 24.5% Na 2 O;
  • BiogranTM 24.5% CaO; 6.0% P 2 O 5 by weight of the composition, and is available as a commercial preparation called BiogranTM by 3i.
  • Another example of a suitable bioactive glass contains 53.0% SiO 2 ; 23.0% Na 2 O; 20.0% CaO; 4.0% P 2 O 5 by weight of the composition, and is available as a commercial preparation called
  • Beta-tricalcium phosphate (beta-TCP) is another well known bone substitute material suitable for use in the present invention. It has been extensively studied and clinically used because its molecular composition is similar to that of human bone. Among bioceramics, beta-TCP has an excellent osteoconductivity, bioactivity and ability to form a strong bone-calcium phosphate interface. In general, clinical application of beta-TCP is limited due to its poor mechanical properties, in particular its low fracture toughness, and its improper degradation properties. These properties do not, however, hinder its use in frontal sinus obliteration since no mechanical properties or fast degradation are required.
  • An osteoinductive material suitable for use in the present invention may also contain a combination of various biomaterials.
  • examples of such combinations include mixtures of a bioactive glass or triclacium phosphate with collagen, poly(lactic-co-glycolic acid) (PLGA) and/or polylactic acid (PLA).
  • composition and the biological regenerate may be supplemented with therapeutic agents such as antibiotic, antiviral and anti- inflammatory agents, and osteoinductive hormones, growth factors and other agents including Bone Morphogenetic Protein 2 and 7 (BPM-2 and -7), vitamin D, dexamethazone, beta-glycerophosphate and ascorbic acid, or any combinations thereof.
  • therapeutic agents such as antibiotic, antiviral and anti- inflammatory agents, and osteoinductive hormones, growth factors and other agents including Bone Morphogenetic Protein 2 and 7 (BPM-2 and -7), vitamin D, dexamethazone, beta-glycerophosphate and ascorbic acid, or any combinations thereof.
  • the composition and the biological regenerate may be prepared by mixing isolated mesenchymal stem cells with a selected osteoinductive material.
  • the cells are preferably pre-cultivated so that they become attached to the osteoinductive material.
  • the cells and the osteoinductive material may be mixed immediately prior to use.
  • at least 50% of the surface of the material is covered by the cells.
  • mesenchymal stem cells promote ossification of osteoinductive bioactive materials.
  • Such an effect is herein demonstrated by a clinical study with patients suffering from severe chronic frontal sinusitis.
  • Administration of adipose tissue derived autogenic stem cells in combination with bioactive glass granules resulted in faster generation of new bone after frontal sinus obliteration as compared to patients treated with bioactive glass granules only.
  • the faster generation of new bone minimizes the risks of re-infections and re-aerations of the frontal sinuses, which are the most feared of complications of obliteration surgery. Long-term infection management was accomplished without any complications.
  • the present invention may be applied to the treatment of chronic frontal sinusitis. It will be obvious to a person skilled in the art that, as technology advances, the inventive concept can be implemented in various ways. The invention and its embodiments are not limited to the examples described below but may vary within the scope of the claims.
  • EXAMPLE 1 Treatment of patients suffering from severe frontal sinus infection with autologous adipose tissue derived stem cells combined with BAG.
  • Patient 1 was a 45-year-old woman with chronic frontal sinusitis problems since 1993. She had been operated with external approach 1993 using abdominal fat obliteration. The patient was asymptomatic 5 years postoperatively, after which she had continuous problems with relapsed disease. Her main symptoms were pain, coloured infectious discharge, and oedema of the frontal head. She went through endonasal sinus operation in 2004 with no relief. She was re-obliterated with autologous stem cells and BAG granules according to the present invention in November 2006 and has been asymptomatic for at least 24 months.
  • Patient 2 was a 36-year-old man who was healthy and sinusitis free until the summer of 2005, when he suffered from prolonged pansinusitis. Since then he had been treated with optimal pharmaceutical and surgical treatments, including frontal sinus trephinations and endonasal sinus surgery three times with no lasting relief. His main symptoms were intensive pain of the frontal head, coloured infectious discharge, and oedema. Frontal sinus obliteration with autologous stem cells and BAG granules according to the present invention was performed in December 2006, and he has been asymptomatic in all control visits postoperatively.
  • the fat was transported to the laboratory for stem cell isolation and expansion.
  • the second operation was performed through a bicoronal incision.
  • the frontal sinus mucosa was removed completely, and the mucosa in the region of the frontonasal ostium was inverted nasally.
  • Adipose tissue stem cells were isolated from subcutaneous adipose tissue using mechanical and enzymatic isolation as described previously (Zuk et al., MoI. Biol. Cell, 13 (2002) 4279-4295; Zuk et al., Tissue Eng., 7 (2001) 21 1-228).
  • the adipose tissue was minced into small fragments and digested with collagenase type I (Invitrogen, Paisley, Scotland, UK). The isolated cells were then maintained seven days in vitro in Dulbecco's Modified Eagle Medium/Ham's Nutrient Mixture F-12 (Invitrogen) with 15 % human serum (Sigma-Aldrich, MO, USA/PAA Laboratories GmbH, Pasching, Austria) without antibiotics, detached with TrypLE Select (Gibco) and prepared for cell transplantation. Prior to combination of BAG and the cells, BAG was incubated with a cell growth medium for 24 hours. Approximately 5x10 6 cells and BAG (20cc/ ⁇ 20ml) were combined just before the surgical operation.
  • the biomaterial used was BiogranTM (3i), with the particle size of 300 to 355 ⁇ m.
  • the composition (by weight) of this bioactive glass is: 45.0% SiO 2 ; 24.5% Na 2 O; 24.5% CaO; 6.0% P 2 O 5 .
  • BonAliveTM (Vivoxid) granules with the particle size of 500 to 800 ⁇ m were used.
  • the composition (by weight) of this bioactive glass is: 53.0% SiO 2 ; 23.0% Na 2 O; 20.0% CaO; 4.0% P 2 O 5 .
  • adipose tissue stem cells were harvested, and analyzed by a fluorescence activated cell sorter (FACSAria, BD Biosciences, Erembodegem, Belgium).
  • the FACS analysis demonstrated that the adipose stem cells from both patients expressed tetraspan protein (CD9), integrin a4 (CD49d), endoglin (CD105), vascular cell adhesion molecule (VCAM; CD106), activated lymphocyte cell adhesion molecule (ALCAM; CD166), hyaluronate (CD44), common acute lymphocytic leukemia antigen (CALLA; CD10), aminopeptidase (CD13) and Thy-1 (CD90).
  • the cells showed weak expression of CD34 and no expression of the hematopoietic markers CD31 or CD45. This marker profile is typical of adipose tissue derived stem cells.
  • the surplus BAG and cell material from the surgical procedure was recovered and maintained in vitro. After seven days in culture, the osteogenic differentiation of cell cultures were determined with a leukocyte alkaline phosphatase (ALP) staining kit (Sigma-Aldrich). DAPI nuclear staining (Vector Laboratories Inc., Burlingame, CA, USA) was used for detecting cell attachment to BAG granules. Both stainings were carried out according to the manufacturers' protocols.
  • ALP leukocyte alkaline phosphatase
  • the histochemical alkaline phosphatase staining revealed that BAG induced osteogenic differentiation of adipose tissue derived stem cells while DAPI staining showed that cells can attach to and grow on BAG granules.

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Abstract

La présente invention concerne des compositions et des régénérats biologiques comprenant des cellules souches mésenchymateuses et des matériaux ostéo-inducteurs, tels que des verres bioactifs et des céramiques vitreux, pour utilisation dans l’oblitération de sinus frontal, et particulièrement dans le traitement de la sinusite frontale chronique. En conséquence, l’invention concerne en outre un procédé de traitement de la sinusite frontale.
PCT/FI2009/050967 2008-12-04 2009-12-01 Régénérat biologique pour utilisation en oblitération WO2010063887A1 (fr)

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US11987608P 2008-12-04 2008-12-04
FI20086161A FI20086161A0 (fi) 2008-12-04 2008-12-04 Obliteraatioon tarkoitettu biologinen regeneraatti
US61/119,876 2008-12-04
FI20086161 2008-12-04

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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