Umbilical cord extracts improve diabetic abnormalities in bone marrow-derived mesenchymal stem cells and increase their therapeutic effects on diabetic nephropathy

Abstract

Bone marrow-derived mesenchymal stem cells (BM-MSC) has been applied as the most valuable source of autologous cell transplantation for various diseases including diabetic complications. However, hyperglycemia may cause abnormalities in intrinsic BM-MSC which might lose sufficient therapeutic effects in diabetic patients. We demonstrated the functional abnormalities in BM-MSC derived from both type 1 and type 2 diabetes models in vitro, which resulted in loss of therapeutic effects in vivo in diabetic nephropathy (DN). Then, we developed a novel method to improve abnormalities in BM-MSC using human umbilical cord extracts, namely Wharton’s jelly extract supernatant (WJs). WJs is a cocktail of growth factors, extracellular matrixes and exosomes, which ameliorates proliferative capacity, motility, mitochondrial degeneration, endoplasmic reticular functions and exosome secretions in both type 1 and type 2 diabetes-derived BM-MSC (DM-MSC). Exosomes contained in WJs were a key factor for this activation, which exerted similar effects to complete WJs. DM-MSC activated by WJs ameliorated renal injury in both type 1 and type 2 DN. In this study, we developed a novel activating method using WJs to significantly increase the therapeutic effect of BM-MSC, which may allow effective autologous cell transplantation.

Use of Human Umbilical Cord and Its Byproducts in Tissue Regeneration

“…Human umbilical cord can be mixed, filtrated or pelleted, the extract increases the in vitro proliferation and migration of fibroblasts, as described in the literature (Van Pham et al, 2014;Bakhtyar et al, 2017;Nagaishi et al, 2017;Saito et al, 2018). Original data from our laboratory have shown that increasing protein concentrations of HUC extract enhance fibroblast proliferation (after 48 h) and migration (16 h) (Figure 2).…”

Mesenchymal Stem Cells Transplantation in Diabetic Kidney Diseases: A Systematic Review and Meta-analysis

“…The treatment based on MSCs from DM mice could not alleviate the kidney damage in DM mice, which might result from abnormal endogenous bone marrow MSCs caused by the high glucose (HG). Monitoring MSCs subsets in the peripheral blood was suggested to predict the diabetic progression and the effectiveness of the therapy [25,37]. Many studies were conducted to gure out the mechanism of MSCs therapy, and one caveat is that a slight move in one part may affect the situation as a whole.…”

“…hUCB-MSCs conditional medium (CM) inhibited NRK-52E EMT induced by TGF-β1 in a concentration-dependent manner [14]. As mentioned before, the dysfunction of stem cells was observed in DM patients, but WJs, a mixture of growth factors, extracellular matrix and exosomes extracted from human umbilical cord, could improve BM-MSCs abnormality in proliferation, cell motility, endoplasmic reticulum, mitochondria degeneration, endoplasmic reticulum function and exosomes secretion [25]. ADSCs-CM decreased the expression of caspase-3, ameliorated podocytes apoptosis in a dose-dependent way and maintained the normal podocytes morphology.…”

“…Various dosages, administration methods, types of MSCs and application frequency were seen in different studies. Furthermore, the source of MSCs should also be taken into account, for the poor therapeutic effect of MSCs from DM mice[25], which indicated that the health of donor also mattered.3. Detection methods: observed indicators and different reference values.…”

Mesenchymal stem cells transplantation reduces diabetic nephropathy

“…The relative mRNA expression of Igf-1 was downregulated, whereas Ifn-γ, Il-1β , Il-2, and Rantes were up-regulated in treated rats as compared to controls. The expressions of α-Sma, which represented the stress fiber of MSCs, was also increased 11 .…”