Human umbilical cord Wharton jelly cells promote extra-pancreatic insulin formation and repair of renal damage in STZ-induced diabetic mice

Abstract

BackgroundWe evaluated the therapeutic effect and fate of high doses of human umbilical cord Wharton jelly cells (hUCWJCs) after IP administration to streptozotocin (STZ)-induced diabetic mice.MethodsType 1 diabetes (T1D) was induced in Kunming mice via IP injection of STZ. hUCWJCs were labeled with 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI). Diabetic animals with sustained hyperglycemia for at least 2 weeks were administered 1 × 107 Dil-hUCWJCs via intraperitoneal injection. Insulin, glucagon and PDX-1 were detected by immunofluorescence with confocal microscopy. Serum mouse and human C-peptide was assayed in blood collected via intracardiac puncture. Specific β-cell differentiation markers and human DNA were assessed using qPCR performed with 200 ng of target DNA.ResultshUCWJCs migrated to the STZ-damaged organs and contributed to lower blood glucose levels in 30% of the treated mice. Confocal microscopy revealed the presence of resident insulin-positive cells in the liver and kidneys. hUCWJC-treated mice with restored hyperglycemia also showed increased serum mouse C-peptide levels. The qPCR results, particularly in the liver, revealed that after transplantation hUCWJCs upregulated genes of endocrine precursors but failed to express endocrine stage markers. Mice with restored hyperglycemia had reduced urinary volume and lacked glomerular hypertrophy, exhibiting a morphology resembling that of normal glomeruli. Moreover, we also verified that one of the possible mechanisms by which hUCWJCs exert immunosuppressive effects is through down-regulation of the cell surface receptor HLA-1.ConclusionsWe confirmed the potential of IP administration of hUCWJCs and the capability of these cells to migrate to damaged tissues and promote insulin secretion from non-pancreatic local cells and to improve renal damage. These findings confer unique therapeutic properties to hUCWJCs, suggesting a promising future in the treatment of diabetes mellitus.Electronic supplementary materialThe online version of this article (10.1186/s12964-017-0199-5) contains supplementary material, which is available to authorized users.

Mouse Umbilical Cord Mesenchymal Stem Cell Paracrine Alleviates Renal Fibrosis in Diabetic Nephropathy by Reducing Myofibroblast Transdifferentiation and Cell Proliferation and Upregulating MMPS in Mesangial Cells

“…Emerging evidence has shown the key roles of paracrine mechanism in ameliorating DN by MSCs [22,30,40,51]. During this process, MSCs can decrease renal fibrosis, suppress oxidative stress, inhibit renal cell injuries, and attenuate adverse inflammatory events and immune response through extracellular vesicles (EVs) [8,30,31,40,51] and secreted soluble factors [52][53][54][55]. For EVs, the contribution of exosomes to MSC therapeutic efficacy has been widely indicated in many different studies [31,51].…”

Articular chondrocyte-derived extracellular vesicles promote cartilage differentiation of human umbilical cord mesenchymal stem cells by activation of autophagy

“…Signed informed consent was obtained from all participants for this study. The isolation of HUCMSCs from the Wharton ' s jelly of the umbilical cords was described previously 35 with minor modi cations. In brief, umbilical cords were obtained from fullterm delivery patients by caesarean section at The First A liated Hospital of Guangxi Medical University.…”

Articular chondrocyte-derived exosomes promote cartilage differentiation of human umbilical cord mesenchymal stem cells by activation of autophagy

“…Signed informed consent was obtained from all participants for this study. The isolation of HUCMSCs from the Wharton ' s jelly of the umbilical cords was described previously 34 with minor modi cations. In brief, umbilical cords were obtained from fullterm delivery patients by caesarean section at The First A liated Hospital of Guangxi Medical University.…”