We studied in vitro differentiation of pancreatic stem and progenitor cells into insulin secreting cells in the model of streptozotocin-induced diabetes in C57Bl/6 mice. Streptozotocin was shown to increase the population of pancreatic oligopotent β-cell precursors (CD45–, TER119–, CD133+, and CD49flow) and did not affect multipotent (stem) progenitor cells (CD45–, TER119–, CD17–, CD309–). During long-term culturing, diabetic multipotent progenitor cells showed high capacity for self-renewal. A population of dithizone-positive (insulin secreting cells) mononuclear cells was obtained releasing insulin after prolonged culturing in suspension enriched with diabetic CD45–, TER119–, CD17–, and CD309– cells. The rate of generation of “new” insulin-producing cells and insulin release in the samples of experimental group considerably exceeded activity of the corresponding processes in the control group.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
S. Bonner-Weir, M. Taneja, G. C. Weir, et al., Proc. Natl. Acad. Sci. USA, 97, No. 14, 7999-8004(2000).
C. H. Chung and F. Levine, Rev. Diabet Stud., 7, No. 2, 124-131 (2010).
J. Dominguez-Bendala, G. Lanzoni, L. Inverardi, and C. Ricordi, Stem Cells Transl. Med., 1, No, 1, 59-63 (2012).
R. Gopurappilly, V. Bhat, and R. Bhonde, J. Cell. Biochem., 114, No. 10, 2240-2247 (2013)
J. F. Habener and V. Stanojevic, Islets, 4, No. 3, 188-198 (2012).
K. Minami, M. Okuno, K. Miyawaki, et al., Proc. Natl. Acad. Sci. USA, 102, No. 42, 15,116-15,121 (2005).
K. Minami and S. Seino, J. Diabetes Invest., 4, No. 2, 131-141 (2013).
F. Mosna, L. Sensebe, and M. Krampera, Stem Cells, 19, No. 10, 1449-1470.
M. Okuno, K. Minami , A. Okumachi, et al., Am. J. Physiol. Endocrinol. Metab., 292, No. 1, E158-E165 (2007).
A. Shiro, M. Yoshikawa, H. Yokota, et al., Stem Cells, 20, No. 4, 284-292 (2002).
T. Sugiyama, R. T. Rodriguez, G. W. McLean, and S. K. Kim, Proc. Natl. Acad. Sci. USA, 104, No. 1, 175-180 (2007).
A. Suzuki, H. Nakauchi, and H. Taniguchi, Diabetes, 53, No. 8, 2143-2152 (2004).
D. Q. Tang, L. Z. Cao, B. R. Burkhardt, et al., Diabetes, 53, No. 7, 1721-1732 (2004).
C. Zanini, S. Bruno, G. Mandili, et al., PLoS One, 6, No. 12, e28175, doi:10.1371/journal.pone.0028175 (2011).
Q. Zhou, A. C. Law, J. Rajagopal, et al., Dev. Cell., 13, No. 1, 103-114 (2007).
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 156, No. 12, pp. 681-686, December, 2013
Rights and permissions
About this article
Cite this article
Skurikhin, E.G., Ermakova, N.N., Khmelevskaya, E.S. et al. Differentiation of Pancreatic Stem and Progenitor β-Cells into Insulin Secreting Cells in Mice with Diabetes Mellitus. Bull Exp Biol Med 156, 726–730 (2014). https://doi.org/10.1007/s10517-014-2434-z
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10517-014-2434-z