Preferencje help
Widoczny [Schowaj] Abstrakt
Liczba wyników
2013 | 18 | 1 |

Tytuł artykułu

Differentiation of mesenchymal stem cells derived from human bone marrow and subcutaneous adipose tissue into pancreatic islet-like clusters in vitro

Warianty tytułu

Języki publikacji



Although stem cells are present in various adult tissues and body fluids, bone marrow has been the most popular source of stem cells for treatment of a wide range of diseases. Recent results for stem cells from adipose tissue have put it in a position to compete for being the leading therapeutic source. The major advantage of these stem cells over their counterparts is their amazing proliferative and differentiation potency. However, their pancreatic lineage transdifferentiation competence was not compared to that for bone marrow-derived stem cells. This study aims to identify an efficient source for transdifferentiation into pancreatic islet-like clusters, which would increase potential application in curative diabetic therapy. The results reveal that mesenchymal stem cells (MSC) derived from bone marrow and subcutaneous adipose tissue can differentiate into pancreatic islet-like clusters, as evidenced by their islet-like morphology, positive dithizone staining and expression of genes such as Nestin, PDX1, Isl 1, Ngn 3, Pax 4 and Insulin. The pancreatic lineage differentiation was further corroborated by positive results in the glucose challenge assay. However, the results indicate that bone marrow-derived MSCs are superior to those from subcutaneous adipose tissue in terms of differentiation into pancreatic islet-like clusters. In conclusion, bone marrow-derived MSC might serve as a better alternative in the treatment of diabetes mellitus than those from adipose tissue.








Opis fizyczny



  • Lifeline Multispeciality Hospitals, Perungudi, Chennai, India


  • 1. Pittenger, M.F., Mackay, A.M., Beck, S.C., Jaiswal, R.K., Douglas, R., Mosca, J.D., Moorman, M.A., Simonetti, D.W., Craig, S. and Marshak, D.R. Multilineage potential of adult human mesenchymal stem cells. Science 284 (1999) 143-147.
  • 2. Horwitz, E.M., Prockop, D.J., Fitzpatrik, L.A., Koo, W.W., Gordon, P.L., Neel, M., Sussman, M., Orchard, P., Marx, J.C., Pyeritz, R.E. and Brenner, M.K. Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nature Med. 5 (1999) 309-313.
  • 3. Nathan, S., Das, D.S., Thambyah, A. and Fen, C. Cell based therapy in the repair of osteochondral defects: A novel use for adipose tissue. Tissue Eng. 9 (2003) 733-744.
  • 4. Garcia-Olmo, D., Garcia-Arranz, M., Herreros, D., Pascual, I., Peiro, C. and Rodriguez-Montes, J.A. A phase 1 clinical trial of the treatment of Crohn’s fistula by adipose mesenchymal stem cell transplantation. Dis. Colon Rectum 48 (2005) 1416-1423.
  • 5. Zuk, P.A., Zhu, M., Mizuno, H., Huang, J., Futrell, J.W., Katz, A.J., Benhaim, P., Lorenz, H.P. and Hedrick, M.H. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 7 (2001) 211-228.
  • 6. Jurgens, W., Oedayrajsingh-Varma, M., Helder, M., ZandiehDoulabi, B., Schouten, T., Kuik, D., Ritt, M. and van Milligen, F. Effect of tissueharvesting site on yield of stem cells derived from adipose tissue: implications for cell-based therapies. Cell Tissue Res. 332 (2008) 415-426.
  • 7. Wild, S., Roglic, G., Green, A., Sicree, R. and King, H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27 (2004) 1047-1053.
  • 8. Shapiro, A.M., Lakey, J.R., Ryan, E.A., Korbutt, G.S., Toth, E., Warnock, G.L., Kneteman, N.M. and Rajotte, R.V. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid free immunosuppressive regimen. N. Engl. J. Med. 343 (2000) 230-238.
  • 9. Yechoor, V. and Chan, L. Minireview: beta cell replacement therapy for diabetes in the 21st century: manipulation of cell fate by directed differentiation. Mol. Endocrinol. 24 (2010) 1501-1511.
  • 10. Tang, D.Q., Cao. L.Z., Burkhardt, B.R., Xia, C.Q., Litherland, S.A., Atkinson,M.A. and Yang, L.J. In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow. Diabetes 53 (2004) 1721-1732.
  • 11. Timper, K., Seboek, D., Eberhardt, M., Linscheid, P., Christ-Crain, M., Keller, U., Muller, B. and Zulewski, H. Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells. Biochem. Biophys. Res. Commun. 341 (2006) 1135-1140.
  • 12. Oh, S.H., Muzzonigro, T.M., Bae, S.H., LaPlante, J.M., Hatch, H.M. and Petersen, B.E. Adult bone marrow-derived cells trans-differentiating into insulin-producing cells for the treatment of type I diabetes. Lab. Invest. 84 (2004) 607-617.
  • 13. Mitchell, J.B., McIntosh, K., Zvonic, S., Garrett, S., Floyd, Z.E., Kloster, A., Halvorsen, Di., Storms, Y., Goh, R.W., Kilroy, B.G., Wu, X. and Gimble, J.M. Immunophenotype of human adipose-derived cells: temporal changes in stromal-associated and stem cell-associated markers. Stem Cells 240 (2006) 376-385.
  • 14. Zhu, Y., Liu, T., Song, K., Fan, X., Ma, X. and Cui, Z. Adipose-derived stem cell: a better stem cell than BMSC. Cell Biochem. Funct. 26 (2008) 664-675.
  • 15. Adipose-derived adult stem cells: isolation, characterization, and differentiation potential. Cytotherapy 5 (2003) 362-369.
  • 16. Bai, X., Yan, Y., Song, Y.H., Seidensticker, M., Rabinovich, B., Metzele, R., Bankson, J.A., Vykoukal, D. and Alt, E. Both cultured and freshly isolated adipose tissue-derived stem cells enhance cardiac function after acute myocardial infarction. Eur. Heart J. 31 (2010) 489-501.
  • 17. Zuk, P.A., Zhu, M., Ashjian, P., De Ugarte, D.A., Huang, J.I., Mizuno, H., Alfonso, Z.C., Fraser, J.K., Benhaim, P. and Hedrick, M.H. Human Adipose Tissue Is a Source of Multipotent Stem Cells. Mol. Biol. Cell 13 (2002) 4279-4295.
  • 18. Rebelatto, C.K., Aguiar, A.M., Moretao, M.P., Senegaglia, A.C., Hansen, P., Barchiki, F., Oliveira, J., Martins, J., Kuligovski, C., Mansur, F., Christofis, A., Amaral, V.F., Brofman, P.S., Goldenberg, S., Nakao L.S. and Correa, A. dissimilar differentiation of mesenchymal stem cells from bone marrow, umbilical cord blood, and adipose tissue. Exp. Biol. Med. 233 (2008) 901-913.
  • 19. Sun, Y., Chen, L., Hou, X.G., Hou W.K., Dong, J.J., Sun, L., Tang, K.X., Wang, B., Song, J., Li, H. and Wang, K.X. Differentiation of bone marrowderived mesenchymal stem cells from diabetic patients into insulinproducing cells in vitro. Chin. Med. J. 120 (2007) 771-776.
  • 20. Okura, H., Komoda, H., Fumimoto, Y., Lee, C.M., Nishida, T., Sawa, Y., and Matsuyama, A. Transdifferentiation of human adipose tissue-derived stromal cells into insulin-producing clusters. J. Artif. Organs 12 (2009) 123-130.
  • 21. Dhanasekaran, M., Indumathi, S., Kanmani, A., Revathy, K.M., Rajkumar, J.S. and Sudarsanam, D. Surface antigenic profiling of stem cells from human omentum fat in comparison with subcutaneous fat and bone marrow. Cytotechnology 64 (2012) 497-509.
  • 22. Bonner-Weir, S. and Sharma, A. Pancreatic stem cells. J. Pathol. 197 (2002) 519-526.
  • 23. Halban, P.A. Cellular sources of new pancreatic beta cells and therapeutic implications for regenerative medicine. Nat. Cell Biol. 6 (2004) 1021-1025.
  • 24. Chelluri, L.K., Kancherla, R., Turlapati, N., Vemuri, S., Debnath, T., Kumar, P., Beevi, S.S. and Kamaraju, R.S. Improved differentiation protocol of rat bone marrow precursors to functional islet like cells. Stem Cell Stud. 1 (2011) 36-41.
  • 25. Sordi, V., Melzi, R., Mercalli, A., Formicola, R., Doglioni, C., Tiboni, F., Ferrari, G., Nano, R., Chwalek, K., Lammert, E., Bonifacio, E., Borg, D. and Piemonti, L. Mesenchymal cells appearing in pancreatic tissue culture are bone marrow-derived stem cells with the capacity to improve transplanted islet function. Stem Cells 28 (2010) 386-386.
  • 26. De Ugarte, D.A., Alfonso, Z., Zuk, P.A., Elbarbury, A., Zhu, M., Ashjian, P., Benhaim, P., Hedrick, M.H. and Fraser, J.K. Differential expression of stem cell mobilization associated-molecules on multi lineage cells from adipose tissue and bone marrow. Immunol. Lett. 89 (2003) 267-270.
  • 27. Reyes, M., Lund, T., Lenvik, T., Aguiar, D., Koodie, L. and Verfaillie, C.M. Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cell. Blood 98 (2001) 2615-2625.
  • 28. Choi, J.B., Uchino, H., Azuma, K., Iwashita, N., Tanaka, Y., Mochizuki, H., Migita, M., Shimada, T., Kawamori, R. and Watada, H. Little evidence of transdifferentiation of bone marrow-derived cells into pancreatic beta cells. Diabetologia 46 (2003) 1366-1374.
  • 29. Lechner, A., Yang, Y.G., Blacken, R.A., Wang, L., Nolan, A.L. and Habener, J.F. No Evidence for significant transdifferentiation of bone marrow into pancreatic beta-cells in vivo. Diabetes 53 (2004) 616-623.

Typ dokumentu



Identyfikator YADDA

JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.