The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
The Antidiabetic Effect of Mesenchymal Stem Cells Is Unrelated to Their Transdifferentiation Potential But to Their Capability to Restore Th1/Th2 Balance and to Modify the Pancreatic Microenvironment
Open accessAbstract
Type 1 diabetes mellitus (T1DM) is a chronic metabolic disease that results from cell-mediated autoimmune destruction of insulin-producing cells. In T1DM animal models, it has been shown that the systemic administration of multipotent mesenchymal stromal cells, also referred as to mesenchymal stem cells (MSCs), results in the regeneration of pancreatic islets. Mechanisms underlying this effect are still poorly understood. Our aims were to assess whether donor MSCs (a) differentiate into pancreatic β-cells and (b) modify systemic and pancreatic pathophysiologic markers of T1DM. After the intravenous administration of 5 × 10(5) syngeneic MSCs, we observed that mice with T1DM reverted their hyperglycemia and presented no donor-derived insulin-producing cells. In contrast, 7 and 65 days post-transplantation, MSCs were engrafted into secondary lymphoid organs. This correlated with a systemic and local reduction in the abundance of autoaggressive T cells together with an increase in regulatory T cells. Additionally, in the pancreas of mice with T1DM treated with MSCs, we observed a cytokine profile shift from proinflammatory to antinflammatory. MSC transplantation did not reduce pancreatic cell apoptosis but recovered local expression and increased the circulating levels of epidermal growth factor, a pancreatic trophic factor. Therefore, the antidiabetic effect of MSCs intravenously administered is unrelated to their transdifferentiation potential but to their capability to restore the balance between Th1 and Th2 immunological responses along with the modification of the pancreatic microenvironment. Our data should be taken into account when designing clinical trials aimed to evaluate MSC transplantation in patients with T1DM since the presence of endogenous precursors seems to be critical in order to restore glycemic control.
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Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F. C., Krause, D. S., Deans, R. J., Keating, A., Prockop, D. J., & Horwitz, E. M. (2006) · Cytotherapy · doi:10.1080/14653240600855905 · Cited by 17,766
Mesenchymal stem cells as trophic mediators
Caplan, A. I., & Dennis, J. E. (2006) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20886 · Cited by 2,992
Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation
Dor, Y., Brown, J., Martinez, O. I., & Melton, D. A. (2004) · Nature · doi:10.1038/nature02520 · Cited by 2,219
Immune modulation by mesenchymal stem cells
Rasmusson, I. (2006) · Experimental Cell Research · doi:10.1016/j.yexcr.2006.03.019 · Cited by 374
Cited by
Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine
Murphy, M. B., Moncivais, K., & Caplan, A. I. (2013) · Experimental & Molecular Medicine · doi:10.1038/emm.2013.94 · Cited by 1,231
Advances in islet encapsulation technologies
Desai, T., & Shea, L. D. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.232 · Cited by 427
Vasandan, A. B., Jahnavi, S., Shashank, C., Prasad, P., Kumar, A., & Prasanna, S. J. (2016) · Scientific Reports · doi:10.1038/srep38308 · Cited by 406
Engineering islets from stem cells for advanced therapies of diabetes
Siehler, J., Blöchinger, A. K., Meier, M., & Lickert, H. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00262-w · Cited by 125
Mesenchymal Stem Cell-Derived Extracellular Vesicles to the Rescue of Renal Injury
Birtwistle, L., Chen, X.-M., & Pollock, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126596 · Cited by 113
Metadata
- Authors
- Ezquer, F., Ezquer, M., Contador, D., Ricca, M., Simon, V., & Conget, P.
- Venue
- STEM CELLS
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-07-24
- Volume
- 30
- Issue
- 8
- Pages
- 1664-1674
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- OpenAlex
- W1981284807
- Cited by
- 162
- References
- 4
- FWCI
- 12.03
- Type
- journal article
- Language
- en
- Open access
- bronze
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