CA2262014A1 - Adipogenic differentiation of human mesenchymal stem cells - Google Patents

Adipogenic differentiation of human mesenchymal stem cells

Info

Publication number
CA2262014A1
CA2262014A1 CA002262014A CA2262014A CA2262014A1 CA 2262014 A1 CA2262014 A1 CA 2262014A1 CA 002262014 A CA002262014 A CA 002262014A CA 2262014 A CA2262014 A CA 2262014A CA 2262014 A1 CA2262014 A1 CA 2262014A1
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CA
Canada
Prior art keywords
camp
mesenchymal stem
composition
compound
cells
Prior art date
Legal status (The legal status 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 status listed.)
Granted
Application number
CA002262014A
Other languages
French (fr)
Other versions
CA2262014C (en
Inventor
Mark F. Pittenger
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Osiris Therapeutics Inc
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Individual
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
Application filed by Individual filed Critical Individual
Publication of CA2262014A1 publication Critical patent/CA2262014A1/en
Application granted granted Critical
Publication of CA2262014C publication Critical patent/CA2262014C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • 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
    • C12N5/0653—Adipocytes; Adipose tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • 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
    • 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
    • C12N5/0663—Bone marrow mesenchymal stem cells (BM-MSC)
    • 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
    • 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
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/01—Modulators of cAMP or cGMP, e.g. non-hydrolysable analogs, phosphodiesterase inhibitors, cholera toxin
    • 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
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/30—Hormones
    • C12N2501/38—Hormones with nuclear receptors
    • C12N2501/39—Steroid hormones

Abstract

A composition which comprises human mesenchymal stem cells which have the potential to differentiate into cells of more than one connective tissue type and a composition which induces cells from the mesenchymal stem cell population to differentiate into the adipogenic lineage, and a process for inducing such differentiation. The composition for inducing such differentiation comprises a glucocorticoid and a compound which stimulates cAMP production or inhibits cAMP degradation (such as a phosphodiesterase inhibitor). The process can further include isolating the adipocytes from remaining hMSCs.

Claims (11)

1. A composition which comprises human mesenchymal stem cells which have the potential to differentiate into cells of more than one connective tissue type and a substance which induces cells from the mesenchymal stem cell population to differentiate into the adipogenic lineage.
2. The composition of claim 1 wherein the substance which induces cells from the mesenchymal stem cell population to differentiate into the adipogenic lineage comprises a glucocorticoid and a member selected from the groups consisting of (i) a compound which elevates intracellular levels of cAMP and (ii) a compound which inhibits degradation of cAMP.
3. The composition of claim 2 wherein the glucocorticoid is selected from the group consisting of dexamethasone, hydrocortisone, and cortisone.
4. The composition of claim 2 wherein the substance which elevates intracellular cAMP include dibutyryl-cAMP, 8-CPT-cAMP (8-(4)-chlorophenylthio)-adenosine 3', 5' cyclic monophosphate; 8-bromo-cAMP; dioctanoyl-cAMP and Forskolin.
5. The composition of claim 2 wherein the substance which inhibits degradation of cAMP is a phosphodiesterase inhibitor selected from the group consisting of methyl isobutylxanthine, theophylline, caffeine, and indomethacin.
6. The composition of claim 2 wherein the substance which induces cells from the mesenchymal stem cell population to differential into the adipogenic lineage further comprises insulin.
7. A process for inducing a human mesenchymal stem cells to differential into adipocytes, comprising:

contacting human mesenchymal stem cells with (i) a glucocorticoid and (ii) a compound which elevates intracellular levels of cAMP, said glucocorticoid and compound being employed in an amount sufficient to induce human mesenchymal stemcells to differentiate into adipocytes.
8. The process of claim 7 wherein (ii) is a compound which inhibits a compound which degrades cAMP.
9. The process of Claim 8 wherein (ii) is a phosphodiesterase inhibitor.
10. The process of Claim 9 wherein (i) and (ii) are in admixture with each other.
11. The process of Claim 7 which further comprises isolating the adipocytes from remaining hMSCs.
CA2262014A 1996-07-30 1997-07-21 Adipogenic differentiation of human mesenchymal stem cells Expired - Fee Related CA2262014C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US08/700,753 US5827740A (en) 1996-07-30 1996-07-30 Adipogenic differentiation of human mesenchymal stem cells
US08/700,753 1996-07-30
PCT/US1997/012356 WO1998004682A1 (en) 1996-07-30 1997-07-21 Adipogenic differentiation of human mesenchymal stem cells

Publications (2)

Publication Number Publication Date
CA2262014A1 true CA2262014A1 (en) 1998-02-05
CA2262014C CA2262014C (en) 2010-09-14

Family

ID=24814738

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2262014A Expired - Fee Related CA2262014C (en) 1996-07-30 1997-07-21 Adipogenic differentiation of human mesenchymal stem cells

Country Status (11)

Country Link
US (3) US5827740A (en)
EP (2) EP1659172A1 (en)
JP (1) JP2001523084A (en)
AT (1) ATE342349T1 (en)
AU (1) AU3729097A (en)
CA (1) CA2262014C (en)
DE (1) DE69736814T2 (en)
DK (1) DK0954565T3 (en)
ES (1) ES2274547T3 (en)
PT (1) PT954565E (en)
WO (1) WO1998004682A1 (en)

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