Differentiation of adipocytes and osteocytes from human adipose and placental mesenchymal stem cells

Document Type: Original Article


1 Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

3 Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

4 Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Stem Cell & Regenerative Medicine Research Group, Department of Clinical Biochemistry, Mashhad University of Medical Sciences, Mashhad, Iran. Department of Clinical Biochemistry, Mashhad University of Medical Sciences, Mashhad, Iran

5 Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.


Objective(s):Mesenchymal stem cells (MSC) can be isolated from adult tissues such as adipose tissue and other sources. Among these sources, adipose tissue (because of easy access) and placenta (due to its immunomodulatory properties, in addition to other useful properties), have attracted more attention in terms of research. The isolation and comparison of MSC from these two sources provides a proper source for clinical experimentation. The aim of this study was to compare the characteristics of MSC isolated from human adipose tissue and placenta.
Materials and Methods: Adipose and placental MSC were isolated from the subcutaneous adipose tissues of 10 healthy women (25 to 40 years) and from a fresh term placenta (n= 1), respectively. Stem cells were characterized and compared by flow cytometry using CD29, CD31, CD34, CD44, CD45, CD105, CD166 and HLA-DR markers. Osteocytes and adipocytes were differentiated from isolated human mesenchymal stem cells (HMSC).
Results: Adipose and placenta-derived MSC exhibited the same morphological features. ADSC differentiated faster than placenta; however, both were differentiated, taking up to 21 days for osteocyte and 14 days for adipocyte differentiation. About 90% of PLC-MSC and ADSC were positive for CD29, CD44, CD105, and CD166; and negative for CD31, CD34, CD45, and HLA-DR.
Conclusion: The two sources of stem cells showed similar surface markers, morphology and differentiation potential and because of their multipotency for differentiating to adipocytes and osteocytes, they can be applied as attractive sources of MSC for regenerative medicine.


1. Nikoozad Z, Ghorbanian MT, Rezaei A. Comparison of the liver function and hepatic specific genes expression in cultured mesenchymal stem cells and hepatocytes. Iran J Basic Med Sci  2014; 17:27-33.

2. Maqbool M, Vidyadaran S, George E, Ramasamy R. Human mesenchymal stem cells protect neutrophils from serum-deprived cell death. Cell Biol Int 2011; 35:1247-1251.

3. Raynaud CM, Maleki M, Lis R, Ahmed B, Al-Azwani I, Malek J, et al. Comprehensive characterization of mesenchymal stem cells from human placenta and fetal membrane and their response to osteoactivin stimulation. Stem Cells Int 2012; 2012:658356.

4. Semenov OV, Koestenbauer S, Riegel M, Zech N, Zimmermann R, Zisch AH, et al. Multipotent mesenchymal stem cells from human placenta: critical parameters for isolation and maintenance of stemness after isolation. Am J Obstet Gynecol 2010; 202:193 e1-193. e13.

5. Barlow S, Brooke G, Chatterjee K, Price G, Pelekanos R, Rossetti T, et al. Comparison of human placenta- and bone marrow-derived multipotent mesenchymal stem cells. Stem Cells Dev 2008; 17:1095-1107.

6. Thomas ED. Bone marrow transplantation: prospects for leukemia and other conditions. Proc Inst Med Chic. 1975;30(8):256-8.

7. Bacigalupo A. Mesenchymal stem cells and haematopoietic stem cell transplantation. Best Pract Res Clin Haematol 2004; 17:387-399.

8. Talaei-Khozani T, Heidari F, Esmaeilpour T, Vojdani Z, Mostafavi-Pour Z, Rohani L. Cardiomyocyte marker expression in mouse embryonic fibroblasts by cell-free cardiomyocyte extract and epigenetic manipulation. Iran J Med Sci 2014; 39:203-212.

9. Efimenko A, Starostina E, Kalinina N, Stolzing A. Angiogenic properties of aged adipose derived mesenchymal stem cells after hypoxic conditioning. J Transl Med 2011; 9:10.

10. Kan I, Melamed E, Offen D. Integral therapeutic potential of bone marrow mesenchymal stem cells. Curr Drug Targets 2005; 6:31-41.

11. Shyu KG, Wang BW, Hung HF, Chang CC, Shih DT. Mesenchymal stem cells are superior to angiogenic growth factor genes for improving myocardial performance in the mouse model of acute myocardial infarction. J Biomed Sci  2006; 13:47-58.

12. Baghaban Eslaminejad M, Fallah N. Small molecule-BIO accelerates and enhances marrow-derived mesenchymal stem cell in vitro chondrogenesis. Iran J Med Sci 2014; 39:107-116.

13. Gronthos S, Franklin DM, Leddy HA, Robey PG, Storms RW, Gimble JM. Surface protein characterization of human adipose tissue-derived stromal cells. J Cell Physiol 2001; 189:54-63.

14. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 2002; 13:4279-4295.

15. Bieback K, Kern S, Kocaomer A, Ferlik K, Bugert P. Comparing mesenchymal stromal cells from different human tissues: bone marrow, adipose tissue and umbilical cord blood. Biomed Mater Eng 2008; 18:S71-S76.

16. De Ugarte DA, Morizono K, Elbarbary A, Alfonso Z, Zuk PA, Zhu M, et al. Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs 2003; 174:101-109.

17. Gimble J, Guilak F. Adipose-derived adult stem cells: isolation, characterization, and differentiation potential. Cytotherapy 2003; 5:362-369.

18. Planat-Benard V, Silvestre JS, Cousin B, Andre M, Nibbelink M, Tamarat R, et al. Plasticity of human adipose lineage cells toward endothelial cells: physiological and therapeutic perspectives. Circulation 2004; 109:656-663.

19. Halvorsen YD, Franklin D, Bond AL, Hitt DC, Auchter C, Boskey AL, et al. Extracellular matrix mineralization and osteoblast gene expression by human adipose tissue-derived stromal cells. Tissue Eng 2001; 7:729-741.

20. De Francesco F, Tirino V, Desiderio V, Ferraro G, D'Andrea F, Giuliano M, et al. Human CD34/CD90 ASCs are capable of growing as sphere clusters, producing high levels of VEGF and forming capillaries. PLoS One 2009; 4:e6537.

21. Timmins NE, Kiel M, Gunther M, Heazlewood C, Doran MR, Brooke G, et al. Closed system isolation and scalable expansion of human placental mesenchymal stem cells. Biotechnol Bioeng 2012; 109:1817-1826.

22. Sun NZ, Ji H. In vitro differentiation of osteocytes and adipocytes from human placenta-derived cells. J Int Med Res 2012; 40:761-767.

23. Kadam S, Muthyala S, Nair P, Bhonde R. Human placenta-derived mesenchymal stem cells and islet-like cell clusters generated from these cells as a novel source for stem cell therapy in diabetes. Rev Diabet Stud 2010; 7:168-182.

24. Vellasamy S, Sandrasaigaran P, Vidyadaran S, George E, Ramasamy R. Isolation and characterisation of mesenchymal stem cells derived from human placenta tissue. World J Stem Cells 2012; 4:53-61.

25. Lee JM, Jung J, Lee HJ, Jeong SJ, Cho KJ, Hwang SG, et al. Comparison of immunomodulatory effects of placenta mesenchymal stem cells with bone marrow and adipose mesenchymal stem cells. Int Immunopharmacol 2012; 13:219-224.

26. Kim BS, Kim JS, Chung YS, Sin YW, Ryu KH, Lee J, et al. Growth and osteogenic differentiation of alveolar human bone marrow-derived mesenchymal stem cells on chitosan/hydroxyapatite composite fabric. J Biomed Mater Res A 2013; 101:1550-1558.

27. Wosnitza M, Hemmrich K, Groger A, Graber S, Pallua N. Plasticity of human adipose stem cells to perform adipogenic and endothelial differentiation. Differentiation 2007; 75:12-23.

28. Kern S, Eichler H, Stoeve J, Kluter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 2006; 24:1294-1301.

29. Sabapathy V, Ravi S, Srivastava V, Srivastava A, Kumar S. Long-term cultured human term placenta-derived mesenchymal stem cells of maternal origin displays plasticity. Stem Cells Int 2012; 2012:174328.

30. Yang XF, He X, He J, Zhang LH, Su XJ, Dong ZY, et al. High efficient isolation and systematic identification of human adipose-derived mesenchymal stem cells. J Biomed Sci 2011; 18:59.

31. Kogler G, Sensken S, Airey JA, Trapp T, Muschen M, Feldhahn N, et al. A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. J Exp Med 2004; 200:123-135.

32. Cao Y, Sun Z, Liao L, Meng Y, Han Q, Zhao RC. Human adipose tissue-derived stem cells differentiate into endothelial cells in vitro and improve postnatal neovascularization in vivo. Biochem Biophys Res Commun 2005; 332:370-379.

33. Loya K, Eggenschwiler R, Ko K, Sgodda M, Andre F, Bleidissel M, et al. Hepatic differentiation of pluripotent stem cells. Biol Chem 2009; 390:1047-1055.

34. Chou MT, Chang SN, Ke C, Chang HI, Sung ML, Kuo HC, et al. The proliferation and differentiation of placental-derived multipotent cells into smooth muscle cells on fibrillar collagen. Biomaterials 2010; 31:4367-4375.

35. Behravan E, Moallem SA, Khateri S, Maraghi E, Jowsey P, Blain PG, et al. Deoxyribonucleic acid damage in Iranian veterans 25 years after wartime exposure to sulfur mustard. J Res Med Sci 2013; 18:239-244.

36. Caviggioli F, Vinci V, Salval A, Klinger M. Human adipose-derived stem cells: isolation, characterization and applications in surgery. ANZ J Surg 2009; 79:856.

37. Parekkadan B, Milwid JM. Mesenchymal stem cells as therapeutics. Annu Rev Biomed Eng 2010; 12:87-117.

38. D'Ippolito G, Schiller PC, Ricordi C, Roos BA, Howard GA. Age-related osteogenic potential of mesenchymal stromal stem cells from human vertebral bone marrow. J Bone Miner Res 1999; 14:1115-1122.

39. Rao MS, Mattson MP. Stem cells and aging: expanding the possibilities. Mech Ageing Dev 2001; 122:713-734.

40. Hass R, Kasper C, Bohm S, Jacobs R. Different populations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-derived MSC. Cell Commun Signal 2011; 9:12.

41. Izadpanah R, Trygg C, Patel B, Kriedt C, Dufour J, Gimble JM, et al. Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue. J Cell Biochem 2006; 99:1285-1297.

42. Yoshimura H, Muneta T, Nimura A, Yokoyama A, Koga H, Sekiya I. Comparison of rat mesenchymal stem cells derived from bone marrow, synovium, periosteum, adipose tissue, and muscle. Cell Tissue Res 2007; 327:449-462.

43. Najar M, Raicevic G, Boufker HI, Kazan HF, Bruyn CD, Meuleman N, et al. Mesenchymal stromal cells use PGE2 to modulate activation and proliferation of lymphocyte subsets: Combined comparison of adipose tissue, Wharton’s Jelly and bone marrow sources. Cell Immunol 2010; 264:171-179. 

44. Yañez R, Oviedo A, Aldea M, Bueren JA, Lamana ML. Prostaglandin E2 plays a key role in the immunosuppressive properties of adipose and bone marrow tissue-derived mesenchymal stromal cells. Exp Cell Res 2010; 316:3109-3123.

45. English K. Mechanisms of mesenchymal stromal cell immunomodulation. Immunol Cell Biol 2012; 91:19-26.

46. Fukuchi Y, Nakajima H, Sugiyama D, Hirose I, Kitamura T, Tsuji K. Human placenta‚Äźderived cells have mesenchymal stem/progenitor cell potential. Stem Cells 2004; 22:649-658.

47. Kim SJ, Song CH, Sung HJ, Yoo YD, Geum DH, Park SH, et al. Human placenta-derived feeders support prolonged undifferentiated propagation of a human embryonic stem cell line, SNUhES3: comparison with human bone marrow-derived feeders. Stem Cells Dev 2007; 16:421-428.

48. Mikkola HK, Gekas C, Orkin SH, Dieterlen-Lievre F. Placenta as a site for hematopoietic stem cell development. Exp Hematol 2005; 33:1048-1054.