Although significant advances have been made in the clinical management of such cases, there is no specific therapy that can improve the rate or effectiveness of the repair process. Recent studies have indicated that adult stem cells, either in the kidney itself or derived from the bone marrow, could participate in this repair process and might therefore be utilized clinically to treat acute renal failure. This review will focus on our current understanding of these stem cells, the controversies surrounding their in vivo capacity to repopulate the renal tubule, and further investigations that will be required before stem cell therapy can be considered for use in the clinical setting (Cantley, 2005). While it remains unknown whether there is a stem cell in the adult kidney, characterization of the cell populations involved in renal repair and misrepair is allowing a new understanding of the mechanisms that are responsible for renal homeostasis (Oliver, 2004). Ischemia-reperfusion injury (I/R injury) is a common cause of acute renal failure. Recovery from I/R injury requires renal tubular regeneration. Hematopoietic stem cells (HSC) have been shown to be capable of differentiating into hepatocytes, cardiac myocytes, gastrointestinal epithelial cells, and vascular endothelial cells during tissue repair. The current study tested the hypothesis that murine HSC can contribute to the regeneration of renal tubular epithelial cells after I/R injury (Lin, 2003). The kidney has the ability to restore the structural and functional integrity of the proximal tubule, which undergoes extensive epithelial cell death after prolonged exposure to ischemia. Small numbers of peritubular endothelial cells to be derived from bone marrow cells that may serve in the repair process (Duffield, 2005). Renal progenitor tubular cells [label-retaining cells (LRC)] are identified in normal kidneys by in vivo bromodeoxyuridine (BrdU) labeling. In normal and contralateral kidneys, LRC are observed scattering among tubular epithelial cells. After unilateral ureteral obstruction (UUO), the number of the LRC significantly increase, and most of them are positive for proliferating cell nuclear antigen (PCNA). In contrast, PCNA+ cells lacking BrdU label are rarely observed. LRC are not only in tubules but also in the interstitium after UUO. Laminin staining showed that a number of the LRC are adjacent to the destroyed tubular basement membrane. Some tubules, including LRC, lose the expression of E-cadherin after UUO. A large number of cell populations expressed vimentin, heat shock protein 47, or alpha-smooth muscle actin in the UUO kidneys, and each population contained LRC. None of the LRC is positive for these fibroblastic markers in contralateral kidneys. When renal tubules from BrdU-treated rats are cultured in the gel, some cells protruded from the periphery of the tubules and migrated into the gel. Most of these cells are BrdU+.
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- Fall '19