Renal Stem Cells

Use of Mesenchymal Stem Cells and Bone Marrow Stem Cells

Regenerating tubular cells in the kidney following acute renal failure were found to behave exactly like stem cells in their characteristics. Therefore, it may be that injection of stem cells into patients could help slow down disease progression. Different stem cell approaches have been used (e.g., bone marrow stem cells [BMSCs] and mesen—chymal stem cells [MSCs]), and now efforts are being made to exploit kidney—specific adult renal stem cells, although this work is only in its early stages. Both MSCs and BMSCs have the ability to grow and expand their colonies in vitro and when injected into humans. They can then migrate to the site of damage and later on express their smooth muscle, endothelial, and epithelial proteins. These cell types provide immunoprotection, but one school of thought suggests that MSCs and BMSCs do not directly replace the damaged cells but, rather, only cause a decrease in inflammation by decreasing the release of inflammatory mediators by interstitium. Unfortunately, there are many problems associated with the use of MSCs and BMSCs. Ethical problems were related with MSCs, and the contribution of BMSCs in renal failure was found to be very small, so the direction of therapeutic research for the treatment of acute renal failure had to be modified.

Adult Renal Stem Cells for the Treatment of Acute Renal Failure

One school of thought proposed that there are renal progenitor—like cells in the kidney and proved it by [Page 471]injecting bromodeoxyuridine (BrdU; a thymidine analogue that stains the nucleus of cells while they are in the active mi to tic phase of cell division) into mice with labeled stem cells in the kidney. These cells were isolated from mice kidneys and were studied for growth and differentiation markers for a few weeks. The cells then demonstrated cell divisions with a slow cycling rate, and the expression of proliferating cell nuclear antigen (PCNA) was noted two hours following ischemia reperfusion injury (IRI) and maxing out at 24 hours following IRI. The number of BrdU labeled retaining cells (LRCs) increased markedly by 24 hours after IRI. All BrdU—positive cells were positive for PCNA as well. In addition, none of the PCNA—positive cells were BrdU negative, which means that all the BrdU—labeled cells were dividing. Mes—enchymal proteins (e.g., vimentin, a component of cellular structure that is responsible for maintaining cellular integrity) and an epithelial protein (E—cadherin, epithelial transmembrane protein—cell adhesion molecule) were expressed after IRI; these proteins were expressed by cells weakly positive for BrdU that were actually descendants of LRCs. After almost a week post—IRI, the number of LRCs decreased, PCNA disappeared, and vimentin and E—cadherin were seen only on the cells that were adjacent to LRCs, but not on LRCs, indicating that these are the differentiated progeny of LRCs. After two weeks of chase period, LRCs were seen in the mesangium and endothelial cells. Capillary endothelial cells release activin—A (a peptide that functions to regulate cell proliferation, differentiation, and morphogenesis), which inhibits transforming growth factor beta and makes these stem cells quiescent in their niches.

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