Adipose-derived stem cells and lattices

• US 20050153441A1
• Filed: 12/17/2003
• Published: 07/14/2005
• Est. Priority Date: 03/10/1999
• Status: Active Grant

• Current Assignee: University of Pittsburgh of The Commonwealth System of Higher Education
• Original Assignee: University of Pittsburgh of The Commonwealth System of Higher Education
• Inventors: Hedrick, Marc H., Katz, Adam J., Zhu, Min, Llull, Ramon, Lorenz, Hermann Peter, Benhaim, Prosper, Futrell, J. William
• Granted Patent: US 7,470,537 B2
• Time in Patent Office: Days
• US Class Current: 435/366
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C12N 2500/25 Insulin-transferrin; Insulin-transferrin-selenium
• CPC Class Codes: C12N 2500/38 Vitamins
• CPC Class Codes: C12N 2500/42 Organic phosphate, e.g. beta glycerophosphate
• CPC Class Codes: C12N 2501/01 Modulators of cAMP or cGMP, e.g. non-hydrolysable analogs, phosphodiesterase inhibitors, cholera toxin
• CPC Class Codes: C12N 2501/15 Transforming growth factor beta (TGF-β)
• CPC Class Codes: C12N 2501/33 Insulin together with transferrin C12N2500/25; Insulin-like growth factors C12N2501/105
• CPC Class Codes: C12N 2501/39 Steroid hormones
• CPC Class Codes: C12N 2510/00 Genetically modified cells
• CPC Class Codes: C12N 2533/90 Substrates of biological origin, e.g. extracellular matrix, decellularised tissue
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: C12N 5/0667 Adipose-derived stem cells [ADSC]; Adipose stromal stem cells

Abstract

The present invention provides adipose-derived stem cells (ADSCs), adipose-derived stem cell-enriched fractions (ADSC-EF) and adipose-derived lattices, alone and combined with the ADSCs of the invention. In one aspect, the present invention provides an ADSC substantially free of adipocytes and red blood cells and clonal populations of connective tissue stem cells. The ADSCs can be employed, alone or within biologically-compatible compositions, to generate differentiated tissues and structures, both in vivo and in vitro. Additionally, the ADSCs can be expanded and cultured to produce molecules such as hormones, and to provide conditioned culture media for supporting the growth and expansion of other cell populations. In another aspect, the present invention provides a adipose-derived lattice substantially devoid of cells, which includes extracellular matrix material from adipose tissue. The lattice can be used as a substrate to facilitate the growth and differentiation of cells, whether in vivo or in vitro, into anlagen or even mature tissues or structures.

Claims

1. An isolated adipose-derived stem cell (ADSC).

2. The stem cell of claim 1, which can be cultured for at least 15 passages without differentiating.

3. The stem cell of claim 1, that is multipotent.

4. The stem cell of claim 3, that differentiates into mesoderm, ectoderm or endoderm.

6. The stem cell of claim 1 which is human.

7. The stem cell of claim 1, which is genetically modified.

8. A defined cell population comprising a plurality of the cell of claim 1.

9. The defined cell population of claim 8 which is homogenous.

10. The defined cell population of claim 8 which is heterogeneous.

11. The defined cell population of claim 8 which is clonal.

12. A progeny cell of the stem cell of claim 4, committed to develop into a mesodermal cell.

13. A progeny cell of the stem cell of claim 4, committed to develop into an ectodermal cell.

14. A progeny cell of the stem cell of claim 4, committed to develop into an endodermal cell.

15. Tissue comprised of the stem cell of claim 4, and differentiated mesodermal cells.

16. Tissue comprised of the stem cell of claim 4, and differentiated ectodermal cells.

17. Tissue comprised of the stem cell of claim 4, and differentiated into endodermal cells.

18. A method of inducing mesodermal tissue comprising culturing the stem cell of claim 4 in a mesoderm-inducing medium.

19. A method of inducing ectodermal tissue comprising culturing the stem cell of claim 4 in a ectoderm-inducing medium.

20. A method of inducing endodermal tissue comprising culturing the stem cell of claim 4 in a endoderm-inducing medium.

21. A method of forming tissue in a subject comprising introducing the progeny cell of claim 12, 13 or 14 into a subject in a sufficient amount to form mesodermal, ectodermal or endodermal tissue in said subject.

22. A method of regenerating or repairing tissue in a subject comprising introducing a stem cell of claim 1, 12, 13 or 14 into a subject in a sufficient amount to regenerate or repair tissue.

31. A composition comprising the cell of claim 1 and a biologically compatible lattice.

32. A composition comprising the cell of claim 1 and the lattice of claim 29 or 30.

33. Progeny of the stem cell of claim 3.

34. A method of delivering a transgene to an animal comprising introducing the stem cell of claim 1 containing a selected transgene into a subject, such that the transgene is expressed in the subject.

35. A method of inducing the differentiation of the cell of claim 1, comprising culturing the cell in a suitable medium effective to induce differentiation under suitable differentiation conditions.

36. The method of claim 35 wherein said medium is a conditioned medium of a specific cell type.

37. A method of inducing the differentiation of the cell of claim 1, comprising co-culturing the cell with a cell of desired lineage.

38. A method of conditioning culture medium comprising contacting the medium with the cell of claim 1.

39. The cultured medium obtained by the method of claim 38.

5. An adipose-derived stem-cell enriched fraction (ADSC-EF) of an adipose tissue sample from a subject, said fraction substantially free of adipocytes.

23. A method for obtaining an adipose-derived stem cell-enriched fraction (ADSC-EF) comprising treating a sample of adipose tissue from a subject to remove adipocytes forming an adipose-derived stem-cell-enriched fraction (ADSC-EF).

24. The adipose-derived stem-cell enriched-fraction (ADSC-EF) obtained by the method of claim 23.

25. The adipose-derived stem cells (ADSCs) obtained by separating said cells from the ADSC-EF of claim 24.

26. The stem cells of claim 25, wherein said stem cells are multipotent.

27. The stem cells of claim 26, wherein said stem cell differentiate into mesoderm, ectoderm, or endoderm.

28. An adipose-derived lattice comprising adipose tissue extracelluar matrix substantially devoid of cells.

29. The lattice of claim 28 which is substantially anhydrous.

30. The lattice of claim 28 which is hydrated.

40. A kit for obtaining adipose-derived stem cells (ADSCs) from adipose tissues of a subject comprising means for separating the ADSCs from the adipose tissue.

41. The kit of claim 40, further comprising a device for isolating adipose tissue from a subject.

42. The kit of claim 40, further comprising a medium for inducing differentiation of the adipose-derived stem cells.

43. The kit of claim 40, further comprising a medium for culturing the ADSCs.