WO2007145442A1 - Composition pour transplantation comprenant des cellules souches adipeuses ou des adipocytes - Google Patents

Composition pour transplantation comprenant des cellules souches adipeuses ou des adipocytes Download PDF

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Publication number
WO2007145442A1
WO2007145442A1 PCT/KR2007/002729 KR2007002729W WO2007145442A1 WO 2007145442 A1 WO2007145442 A1 WO 2007145442A1 KR 2007002729 W KR2007002729 W KR 2007002729W WO 2007145442 A1 WO2007145442 A1 WO 2007145442A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
transplantation
adipocytes
adipose
stem cells
Prior art date
Application number
PCT/KR2007/002729
Other languages
English (en)
Inventor
Byung Rok Do
Ji Hyang Kim
Sung Goo Kang
Chul Geun Kim
Hyuck Chan Kwon
Un Sang Chang
Hae Kwon Kim
Original Assignee
Infitron, Inc.
Hurimbiocell Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from KR1020070043363A external-priority patent/KR100803576B1/ko
Application filed by Infitron, Inc., Hurimbiocell Co., Ltd. filed Critical Infitron, Inc.
Priority to US12/304,813 priority Critical patent/US20100028310A1/en
Publication of WO2007145442A1 publication Critical patent/WO2007145442A1/fr

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Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06Animal cells or tissues; Human cells or tissues
    • C12N5/0602Vertebrate cells
    • C12N5/0652Cells of skeletal and connective tissues; Mesenchyme
    • C12N5/0653Adipocytes; Adipose tissue
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2533/00Supports or coatings for cell culture, characterised by material
    • C12N2533/50Proteins
    • C12N2533/54Collagen; Gelatin
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2533/00Supports or coatings for cell culture, characterised by material
    • C12N2533/70Polysaccharides

Definitions

  • the present invention relates to a stable composition for transplantation
  • adipose stem cells comprising adipose stem cells, adipocytes, separated adipose tissues (aspirated fat
  • subcutaneous fat separated for example, from the abdomen or the legs for the
  • subcutaneous fat transplantation is performed by separating subcutaneous fat using
  • Subcutaneous fat is separated by
  • adipocytes present within adipose tissues mass may not be able to
  • adipose stem cells for transplantation it may be able to overcome the problem due
  • stem cells are provided to a direct transplantation of subcutaneous fat to a patient. Further, stem cells
  • derived from fat e.g., adipose stem cells
  • adipocytes derived from fat, e.g., adipose stem cells
  • the volumes may increase about 1,000 times
  • adipocytes and/ or adipose stem cells in a normal (physiological) saline solution adipocytes and/ or adipose stem cells in a normal (physiological) saline solution
  • the aforementioned cells may easily precipitate, thus
  • transplantations at hips or breasts which require a relatively large amount of material.
  • stem cells may be extracted using some of extracted adipose tissues and mixing them with the extracted adipose tissues to
  • this method also has a
  • adipocytes, adipose stem cells and/ or adipose tissues are included in transplantation, where adipocytes, adipose stem cells and/ or adipose tissues.
  • adipocytes and/ or adipose stem cells can be stably dispersed in a medium such as a
  • a living body organ or a biodegradable substance such as hyaluronic acid,
  • albumin albumin, collagen, elastin and chondroitin sulfate with high viscosity.
  • the present invention relates to a stable composition for
  • transplantation comprising adipocytes, adipose stem cells and/ or adipose tissues.
  • composition for transplantation comprising (a) a transplant-cell selected from the
  • hyaluronic acid selected from the group consisting of hyaluronic acid, collagen, thrombin, elastin, chondroitin sulfate, albumin and a mixture thereof, in a physiologically compatible
  • adipocytes adipose stem cells and adipose tissues
  • adipose stem cells may be separated from adipose tissues by means of liposuction,
  • physiologically compatible buffer solution comprises
  • composition herein may comprise, as a transplant cell, each of adipose stem
  • adipocytes adipocytes, adipose tissues; a mixture of adipocytes and adipose stem cells; a
  • adipose tissues adipose tissues; or a mixture of adipose stem cells adipocytes and adipose tissues.
  • composition may serve the purpose of transplantation and may also increase the
  • adipose stem cells may be differentiated and grown to promote the volumetric growth of the transplanted
  • damaged adipocytes means to treat the substance so that oil or cell debris derived
  • from adipocytes may remain in the amount of less than 30%, less than 20%, less than
  • adipose stem cells adipose stem cells, adipocytes, adipose tissues and a mixture
  • composition herein may be determined considering the physical
  • adipocytes may be transplanted in the
  • Adipose stem cells may be
  • stem cells are used, they may be mixed without limitation within the
  • stem cells are used, about 50 mL of adipocytes and about IxIO 5 cells of adipose stem cells may be used.
  • a biodegradable substance is a stabilizer for stably dispersing the transplant cells.
  • body or a biodegradable substance include hyaluronic acid, collagen, thrombin,
  • collagen is preferred. Hyaluronic acid, collagen, thrombin, elastin, chondroitin
  • sulfate or albumin is derived from a living body, and naturally degrades in a body.
  • composition for transplantation herein may be endowed with a semi-floating
  • biodegradable substance is not limited to a substance derived from a living body in
  • adipocytes adipose stem cells and/ or adipose
  • substance contained in a composition herein is preferred to have a predetermined
  • adipocytes, adipose stem cells and/ or adipose tissues may be stably dispersed.
  • composition herein contains only adipose stem cells as a
  • biodegradable substance may be contained in an amount of about 0.001-20 wt%
  • composition herein contains adipocytes and/ or adipose
  • biodegradable substance may be contained in an amount of about 0.0001-10 wt%
  • composition herein may comprise the semi-solid substance derived from a
  • hyaluronic acid or collagen may be preferred.
  • Hyaluronic acid is a biodegradable polymer derived from a living body
  • KFDA Korean Food and Drug Administration
  • USFDA US Food and Drug Administration
  • hyaluronic acid can be selected from the group consisting of a
  • Hyaluronic acid a chemically synthesized hyaluronic acid.
  • hyaluronic acid may be modified depending on the content, i.e., concentration, of hyaluronic acid in
  • Collagen is a scleroprotein contained in large amount in bones, cartilage,
  • collagen when melted.
  • collagen may be selected among collagen
  • Collagen may have a molecular weight of
  • Albumin is present in large amount in blood of mammals including human.
  • albumin may be selected among albumin obtained from
  • body fluids of a mammal including human and albumin prepared by cultivating
  • albumin is any substance that is present in the present invention.
  • albumin is
  • adipocytes and/ or adipose stem cells may be stably dispersed.
  • This concentration is higher than that of the semi-solid substance derived from a
  • albumin may be any substance that is, for example, albumin may be any substance that is, for example, albumin.
  • 0.05-50 wt% preferably 1-30 wt%, more preferably
  • albumin may
  • albumin for example albumin human fraction V (Promega,
  • composition herein may optionally comprise pharmaceutically acceptable
  • additives examples include without limitation an isotonic agent
  • dextran such as dextran and a soothing agent such as benzyl alcohol.
  • a soothing agent such as benzyl alcohol.
  • composition herein comprises adipose stem cells, adipocytes and/ or
  • adipose tissues that are stably dispersed without floating or precipitating in a
  • composition for transplantation of the present invention enables the minute control of the content of
  • transplant cell and may be injected into various transplantation areas in an exact
  • transplant cells prevents non-uniform
  • adipose stem cells transplantation of adipose stem cells, adipocytes and/ or adipose tissues.
  • the spaces of the transplanted cells, stem cells and adipocytes may easily receive
  • the introduced adipocytes and stem cells may extend through the pre-existing
  • adipose tissues and connective tissues and be assisted by the blood vessels, thereby
  • FIG 1 shows the separation of two layers generated when the collected
  • adipose tissues were added with a physiological buffer solution, wherein the upper
  • one is adipose tissues layer, and the lower one is a layer comprising body fluids
  • the red-colored layer is a mixture of body
  • Figure 2 shows the separation of layers after the removal of body fluids
  • the upper layer is adipose tissues layer and the lower one is a layer having a
  • Figure 3 shows the separation of layers after the adipose tissues were treated
  • collagenase wherein the upper layer is an oil layer derived from damaged
  • the intermediate layer is an adipocyte layer
  • the lower layer is an adipocyte layer
  • Figure 4 shows the separation of a composition for transplantation according
  • Figure 5a is a graph showing the weight percentages of adipose stem cells
  • transplantation was divided into the uppermost layer, the upper intermediate layer,
  • composition for transplantation containing adipose stem cells, a physiological saline
  • composition without a biodegradable stabilizer for transplantation (without
  • Figure 5b is a graph showing the distribution of adipose stem cells contained
  • composition for transplantation was divided into the uppermost layer, the upper
  • Figure 6 is a graph showing the weight percentages of adipocytes contained
  • Figure 7 shows the microphotographs, taken immediately after the
  • Figure 8 shows the microphotographs, taken immediately after the
  • transplantation containing no semi-solid substance derived from a living body containing no semi-solid substance derived from a living body.
  • Example 1 Collection of adipocytes and adipose stem cells
  • Adipose tissues which had been removed from a patient through liposuction
  • adipose tissues were added with a physiological
  • Figure 1 shows the separation of the collected adipose tissues added with
  • adipose tissues after the triple treatment of a physiological buffer solution.
  • adipose tissues float, and a substance derived from blood such as
  • adipose tissues contained non-uniform adipocytes, and are thus hard to be
  • the adipocyte layer and the adipose stem cell layer were separated, and each layer was added with a physiological saline solution to remove
  • collagenase The adipose tissues were treated with collagenase, and divided into
  • an oil layer (upper portion), an adipocyte layer (middle portion) and an adipose
  • adipocytes and disrupted fat cells derived oil generated during the collection and
  • Example 2 Preparation of composition for transplantation containing adipose
  • composition for transplantation containing adipose stem cells was
  • stem cells (IxIO 7 ) prepared in Example 1 in 2.5 mL of 2 wt% hyaluronic acid for
  • transplantation prepared by using 2.5 mL of a physiological buffer solution 2.5mL in
  • Example 2 instead of the hyaluronic acid for medical purpose. As compared to the
  • Example 3 Preparation of composition for transplantation containing adipocytes
  • a composition for transplantation containing adipocytes by adding 15 mL of
  • composition for transplantation containing no semi-floating substance
  • Example 4 Preparation of composition for transplantation containing adipocytes
  • a composition for transplantation containing adipocytes and adipose stem containing adipocytes and adipose stem
  • adipose stem cells IxIO 7
  • 15 mL of adipocytes prepared in Example 1 in 0.5 mL of 2% hyaluronic acid having a weight average molecular weight of 300,000 for
  • FIG. 4 shows the separation of the composition for transplantation of the
  • Example 1 adipocytes and adipose stem cells prepared in Example 1.
  • Example 5 Preparation of composition for transplantation containing adipose
  • Collagen having a molecular weight of 130 kDa was dissolved in a
  • composition for transplantation containing adipose stem cells.
  • Example 6 Preparation of composition for transplantation containing adipocytes
  • composition for transplantation containing adipocytes and adipose stem cells
  • Example 7 Preparation of composition for transplantation containing adipose
  • a composition for transplantation was prepared by adding 0.5 mL of a
  • Example 1 and 15 mL of washed adipose tissues separated from a patient, which
  • adipocytes are uniformly present in the uppermost layer and the lowermost
  • the transplantation composition of the present invention comprises stably
  • adipose stem cells dispersed adipose stem cells, adipocytes and/ or adipose tissues in a physiologically compatible physiological saline solution without showing a supernatant or
  • composition of the present invention enables a precise control of the content of
  • transplant cells and may be injected into various transplantation regions in an exact

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • Chemical & Material Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Rheumatology (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Cell Biology (AREA)
  • Materials For Medical Uses (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

La présente invention concerne une composition pour transplantation dans une solution tampon physiologiquement compatible comprenant, (a) une cellule à transplanter choisie parmi une cellule souche adipeuse, un adipocyte, des tissus adipeux (tissu graisseux) et un mélange de ceux-ci; et (b) une substance semi-solide dérivée d'un organisme vivant ou une substance biodégradable choisie par l'acide hyaluronique, le collagène, l'élastine, la thrombine, le sulfate de chondroïtine, l'albumine et un mélange de ceux-ci.
PCT/KR2007/002729 2006-06-14 2007-06-05 Composition pour transplantation comprenant des cellules souches adipeuses ou des adipocytes WO2007145442A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US12/304,813 US20100028310A1 (en) 2006-06-14 2007-06-05 Composition for Transplantation Comprising Adipose Stem Cells or Adipocytes

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR20060053247 2006-06-14
KR10-2006-0053247 2006-06-14
KR10-2007-0043363 2007-05-04
KR1020070043363A KR100803576B1 (ko) 2006-06-14 2007-05-04 지방줄기세포 및 지방세포를 포함한 이식용 조성물

Publications (1)

Publication Number Publication Date
WO2007145442A1 true WO2007145442A1 (fr) 2007-12-21

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITMI20081464A1 (it) * 2008-08-05 2010-02-06 Bint Srl Bio Info Nano Tecnologie Utilizzo di adipociti maturi isolati in medicina rigenerativa per la ricostituzione e la riparazione dei tessuti
US9062288B2 (en) 2008-08-22 2015-06-23 Regeneus Ltd Therapeutic methods using adipose tissue-derived cell suspensions comprising adipocytes

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003053346A2 (fr) * 2001-12-07 2003-07-03 Macropore Biosurgery, Inc. Systemes et methodes de traitement de patients ayant des cellules aspirees par liposuccion traitees
WO2003084468A2 (fr) * 2002-04-03 2003-10-16 Artecel Sciences, Inc. Ameliorations apportees a des cellules souches adultes differenciees derivees du tissu adipeux et leurs utilisations

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003053346A2 (fr) * 2001-12-07 2003-07-03 Macropore Biosurgery, Inc. Systemes et methodes de traitement de patients ayant des cellules aspirees par liposuccion traitees
WO2003084468A2 (fr) * 2002-04-03 2003-10-16 Artecel Sciences, Inc. Ameliorations apportees a des cellules souches adultes differenciees derivees du tissu adipeux et leurs utilisations

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SUGIHARA ET AL.: "Unilocular fat cells in three-dimensional collagen gel matrix culture", JOURNAL OF LIPID RESEARCH, vol. 29, no. 5, 1988, pages 691 - 697, XP002912191 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITMI20081464A1 (it) * 2008-08-05 2010-02-06 Bint Srl Bio Info Nano Tecnologie Utilizzo di adipociti maturi isolati in medicina rigenerativa per la ricostituzione e la riparazione dei tessuti
WO2010016083A1 (fr) * 2008-08-05 2010-02-11 Bint S.R.L. Bio-Info-Nano-Tecnologie Utilisation d'adipocytes matures isolés en médecine régénérative pour la reconstruction et la réparation de tissus
US9062288B2 (en) 2008-08-22 2015-06-23 Regeneus Ltd Therapeutic methods using adipose tissue-derived cell suspensions comprising adipocytes

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