Published online Feb 26, 2020. doi: 10.4252/wjsc.v12.i2.139
Peer-review started: August 27, 2019
First decision: October 19, 2019
Revised: December 27, 2019
Accepted: January 6, 2020
Article in press: January 6, 2020
Published online: February 26, 2020
Despite the availability of current therapies, including oral antidiabetic drugs and insulin, to control the symptoms caused by high blood glucose, it is difficult to cure diabetes mellitus, especially type 1 diabetes mellitus.
Both islet transplantation and cadaveric whole pancreas transplantation are the treatment choice for diabetes. However, shortage of donors, high perioperative risks, and the long-term postoperative need of immunosuppressants are some of the major concerns and challenges for these treatments. More appropriate and effective medical technologies to cure diabetes are needed. Cell therapies using mesenchymal stem cells (MSCs) may be a promising option.
In this study, we tried to figure out the therapeutic mechanisms by which MSCs exert their effects for diabetic rats.
We used three types of differentiation media over 10 d to generate insulin-producing cells (IPCs) from human Wharton’s jelly MSCs (hWJ-MSCs). We further transplanted the undifferentiated hWJ-MSCs and differentiated IPCs derived from them into the portal vein of rats with streptozotocin-induced diabetes and recorded the physiological and pathological changes.
Using fluorescent staining and C-peptide ELISA, we have shown that we were able to successfully induce the differentiation of hWJ-MSCs into IPCs. Transplantation of both IPCs derived from hWJ-MSCs and undifferentiated hWJ-MSCs had the therapeutic effect of ameliorating blood glucose levels and improving intraperitoneal glucose tolerance tests. The transplanted IPCs homed to the pancreas and functionally survived for at least 8 wk after transplantation, whereas the undifferentiated hWJ-MSCs were able to improve the insulitis and ameliorate the serum inflammatory cytokine in streptozotocin-induced diabetic rats.
The therapeutic mechanism of differentiated and undifferentiated human hWJ-MSCs in streptozotocin-induced diabetic rats may be different. Differentiated IPCs can significantly improve blood glucose levels due to continuously secretion insulin by the transplanted cells that survived in the islets of diabetic rats. Transplantation of undifferentiated hWJ-MSCs can significantly improve insulitis and re-balance the inflammatory condition with only a slight improvement in blood glucose levels.
The results of this study will provide basic and essential information for future application of cell regenerative therapy in diabetic patients.