Comparison of multipotency and molecular profile of MSCs between CKD and healthy rats

Abstract

We previously showed that mesenchymal stem cells (MSCs) can differentiate into a functional miniature kidney, suggesting that MSCs may be a cell source for kidney regeneration. However, MSCs from long-term dialysis patients, which have been exposed to uremic toxin, can exhibit reduced viability. Therefore, the aim of this study was to examine the gene expression profiles and differentiation capabilities of bone marrow- and adipose-derived MSCs from chronic kidney disease (CKD) model rats. CKD was induced in rats by adenine feeding, and then MSCs were isolated from bone marrow (BMSCs) and adipose tissue (ASCs). After confirming MSC surface marker expression, comprehensive gene expression profiles were obtained by RT-PCR array. MSCs were differentiated into adipocytes, osteoblasts, and chondrocytes, and histological and/or functional assays were performed. Tgfb3 expression was up-regulated, while Bmp6, Gdf15, Mmp2, and Vegfa were down-regulated in CKD-ASCs compared with Control-ASCs. There were no significant differences in the gene expression of stemness markers, and the morphology of cells that underwent adipogenesis, osteogenesis, and chondrogenesis, or GPDH activity between CKD and control groups. Comparing BMSCs with ASCs, gene expression of Bglap, Bmp4, Igf1, Itgax, Pparg, Ptprc, and Tnf were up-regulated, while Col1a1, Mmp2, Sox9, and Vegfa were down-regulated in both CKD and control groups. Uremic toxin in CKD rats had a small effect on the gene expression and differentiation of MSCs. However, long-term exposure to uremic toxin and the differences in gene expression of MSCs derived from bone marrow or adipose tissue may affect renal regeneration.

The Effects of Indoxyl Sulfate on Human Umbilical Cord-Derived Mesenchymal Stem Cells In Vitro

“…Our present results support the observation that the isolated and expanded bone marrow-derived MSCs from ESRD patients and healthy controls are phenotypically similar [35]. It was found that CKD in model rats had a small effect on the gene expression and differentiation of MSCs [36]. However, long-term exposure to the uremic toxin may affect the surface marker and gene expression of MSCs derived from bone marrow and umbilical cord.…”

Uremia Induces Dental Pulp Ossification but Reciprocally Inhibits Adjacent Alveolar Bone Osteogenesis

“…Meanwhile, Dkk-1 expression was downregulated during the osteogenic differentiation of aortic myofibroblasts [44,48], which is in accordance with the gene expression profile of uremic pulp in the present study. Furthermore, previous studies have demonstrated that the regenerative capability of stem cells derived from CKD subjects was impaired [27,50], which is consistent with stem cell paucity observed in uremic pulp. Therefore, our results provide another evidence that stem cell perturbation plays an important role in uremic ectopic ossifications.…”

Recent Progress in Stem Cell Therapy for Diabetic Nephropathy

“…Furthermore, aging and aging-related disorders significantly impair the survival and differentiation potential of bone marrow MSCs [38][39][40][41] . Bone marrow MSCs isolated from chronic heart disease patients and chronic kidney disease rat models displayed a reduced proliferation and differentiation capacity [41][42][43] , limiting their therapeutic efficacy.…”