Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Cellular and Molecular Biology Letters

Editor-in-Chief: /

IMPACT FACTOR 2016: 1.260
5-year IMPACT FACTOR: 1.506

CiteScore 2016: 1.56

SCImago Journal Rank (SJR) 2016: 0.615
Source Normalized Impact per Paper (SNIP) 2016: 0.470

See all formats and pricing
More options …
Volume 18, Issue 1 (Mar 2013)

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

Dhanasekaran Marappagounder / Indumathi Somasundaram / Sudarsanam Dorairaj / Rajkumar Sankaran
Published Online: 2012-12-28 | DOI: https://doi.org/10.2478/s11658-012-0040-5


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.

Keywords: Diabetes; Islet-like clusters; Bone marrow; Subcutaneous fat; Mesenchymal stem cells; Transdifferentiation; Flow cytometry; Intracellular staining; Dithizone staining; Glucose challenge assay

  • [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. http://dx.doi.org/10.1126/science.284.5411.143CrossrefGoogle Scholar

  • [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. http://dx.doi.org/10.1038/6529CrossrefGoogle Scholar

  • [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. http://dx.doi.org/10.1089/107632703768247412CrossrefGoogle Scholar

  • [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. http://dx.doi.org/10.1007/s10350-005-0052-6CrossrefGoogle Scholar

  • [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. http://dx.doi.org/10.1089/107632701300062859CrossrefGoogle Scholar

  • [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. http://dx.doi.org/10.1007/s00441-007-0555-7CrossrefWeb of ScienceGoogle Scholar

  • [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. http://dx.doi.org/10.2337/diacare.27.5.1047CrossrefGoogle Scholar

  • [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. http://dx.doi.org/10.1056/NEJM200007273430401CrossrefGoogle Scholar

  • [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. http://dx.doi.org/10.1210/me.2009-0311CrossrefWeb of ScienceGoogle Scholar

  • [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. http://dx.doi.org/10.2337/diabetes.53.7.1721CrossrefGoogle Scholar

  • [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. http://dx.doi.org/10.1016/j.bbrc.2006.01.072CrossrefGoogle Scholar

  • [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. http://dx.doi.org/10.1038/labinvest.3700074CrossrefGoogle Scholar

  • [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. http://dx.doi.org/10.1634/stemcells.2005-0234CrossrefGoogle Scholar

  • [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. http://dx.doi.org/10.1002/cbf.1488CrossrefWeb of ScienceGoogle Scholar

  • [15] Adipose-derived adult stem cells: isolation, characterization, and differentiation potential. Cytotherapy 5 (2003) 362–369. Google Scholar

  • [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. http://dx.doi.org/10.1093/eurheartj/ehp568CrossrefGoogle Scholar

  • [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. http://dx.doi.org/10.1091/mbc.E02-02-0105CrossrefGoogle Scholar

  • [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. http://dx.doi.org/10.3181/0712-RM-356CrossrefGoogle Scholar

  • [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. Google Scholar

  • [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. http://dx.doi.org/10.1007/s10047-009-0455-6Web of ScienceCrossrefGoogle Scholar

  • [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. http://dx.doi.org/10.1007/s10616-012-9427-4CrossrefWeb of ScienceGoogle Scholar

  • [22] Bonner-Weir, S. and Sharma, A. Pancreatic stem cells. J. Pathol. 197 (2002) 519–526. http://dx.doi.org/10.1002/path.1158CrossrefGoogle Scholar

  • [23] Halban, P.A. Cellular sources of new pancreatic beta cells and therapeutic implications for regenerative medicine. Nat. Cell Biol. 6 (2004) 1021–1025. http://dx.doi.org/10.1038/ncb1104-1021CrossrefGoogle Scholar

  • [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. http://dx.doi.org/10.4081/scs.2011.e5CrossrefGoogle Scholar

  • [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. http://dx.doi.org/10.1002/stem.314Web of ScienceCrossrefGoogle Scholar

  • [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. http://dx.doi.org/10.1016/S0165-2478(03)00108-1CrossrefGoogle Scholar

  • [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. http://dx.doi.org/10.1182/blood.V98.9.2615CrossrefGoogle Scholar

  • [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. http://dx.doi.org/10.1007/s00125-003-1182-9CrossrefGoogle Scholar

  • [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. http://dx.doi.org/10.2337/diabetes.53.3.616CrossrefGoogle Scholar

About the article

Published Online: 2012-12-28

Published in Print: 2013-03-01

Citation Information: Cellular and Molecular Biology Letters, ISSN (Online) 1689-1392, DOI: https://doi.org/10.2478/s11658-012-0040-5.

Export Citation

© 2012 Versita Warsaw. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Louise Cleal, Teodora Aldea, and You-Ying Chau
Adipocyte, 2017, Page 00
Chunling Wu, Feilin Liu, Pengdong Li, Guifang Zhao, Shaowei Lan, Wenyue Jiang, Xiangwei Meng, Lixing Tian, Gang Li, Yulin Li, and Jin Yu Liu
Cell Transplantation, 2015, Volume 24, Number 5, Page 891
Juan A. Guadix, José L. Zugaza, and Patricia Gálvez-Martín
Medicina Clínica (English Edition), 2017, Volume 148, Number 9, Page 408
Mahmoud M. Gabr, Mahmoud M. Zakaria, Ayman F. Refaie, Engy A. Abdel-Rahman, Asmaa M. Reda, Sameh S. Ali, Sherry M. Khater, Sylvia A. Ashamallah, Amani M. Ismail, Hossam El-Din A. Ismail, Nagwa El-Badri, and Mohamed A. Ghoneim
BioMed Research International, 2017, Volume 2017, Page 1
Arefeh Jafarian, Mohammad Taghikani, Saeid Abroun, Amir Allahverdi, Maryam Lamei, Niknam Lakpour, Masoud Soleimani, and Giovanni Camussi
PLOS ONE, 2015, Volume 10, Number 6, Page e0128650
Juan A. Guadix, José L. Zugaza, and Patricia Gálvez-Martín
Medicina Clínica, 2017, Volume 148, Number 9, Page 408
Arianna Scuteri, Elisabetta Donzelli, Virginia Rodriguez-Menendez, Maddalena Ravasi, Marianna Monfrini, Barbara Bonandrini, Marina Figliuzzi, Andrea Remuzzi, Giovanni Tredici, and Paolo Fiorina
PLoS ONE, 2014, Volume 9, Number 1, Page e84309
Dominique L. Doster, Amanda R. Jensen, Sina Khaneki, and Troy A. Markel
Cytotherapy, 2016, Volume 18, Number 12, Page 1457
Katarzyna Siennicka, Aleksandra Zolocinska, Karolina Stepien, Natalia Lubina-Dabrowska, Marzena Maciagowska, Ewa Zolocinska, Anna Slysz, Renata Piusinska-Macoch, Slawomir Mazur, Urszula Zdanowicz, Robert Smigielski, Adam Stepien, and Zygmunt Pojda
Stem Cells International, 2016, Volume 2016, Page 1
Nadine E. Rekittke, Meidjie Ang, Divya Rawat, Rahul Khatri, and Thomas Linn
Stem Cells International, 2016, Volume 2016, Page 1
M.A. Wassef, H. Fouad, D. Sabry, N. Afifi, A.M. Abbas, W. Mostafa, and S.H. Ahmed
Biochemistry and Biophysics Reports, 2016, Volume 5, Page 468
Molecular Medicine Reports, 2015, Volume 12, Number 3, Page 3345
Mingjun Cao, Qingjie Pan, Huansheng Dong, Xinxu Yuan, Yang Li, Zhen Sun, Xiao Dong, and Hongjun Wang
Stem Cell Research & Therapy, 2015, Volume 6, Number 1
Hossein Salehi, Noushin Amirpour, Ali Niapour, and Shahnaz Razavi
Stem Cell Reviews and Reports, 2016, Volume 12, Number 1, Page 26
Helen P. Makarenkova and Darlene A. Dartt
Current Molecular Biology Reports, 2015, Volume 1, Number 3, Page 115
Loan Thi-Tung Dang, Anh Nguyen-Tu Bui, Vuong Minh Pham, Ngoc Kim Phan, and Phuc Van Pham
Biomedical Research and Therapy, 2015, Volume 2, Number 1
Anahita Shaer, Negar Azarpira, Akbar Vahdati, Mohammad Karimi, and Mehrdad Shariati
Cellular and Molecular Biology Letters, 2014, Volume 19, Number 3
Mahmoud M. Gabr, Mahmoud M. Zakaria, Ayman F. Refaie, Sherry M. Khater, Sylvia A. Ashamallah, Amani M. Ismail, Nagwa El-Badri, and Mohamed A. Ghoneim
BioMed Research International, 2014, Volume 2014, Page 1
Izabela Harasymiak-Krzyżanowska, Alicja Niedojadło, Jolanta Karwat, Lidia Kotuła, Paulina Gil-Kulik, Magdalena Sawiuk, and Janusz Kocki
Cellular and Molecular Biology Letters, 2013, Volume 18, Number 4

Comments (0)

Please log in or register to comment.
Log in