| Stem cells were believed to be lineage restricted and organ specific. However, recent studies have demonstrated that bone marrow derived stem cells from both mice and humans have the ability to cross lineage boundaries, expressing tissue specific proteins in organs such as heart, liver, brain, skeletal muscle, vascular endothelium, pneumocyte, et al. Bone marrow-derived stem cells (BMSCs) transplantation is employed as cell therapy in the animal models of myocardial infarction and BMSCs are found to be signaled and recruited to the injured heart where they undergo differentiation and may participate in the regeneration of myocardial cells. In clinical study, the selective intracoronary transplantation of autologous mononuclear bone marrow cells is proved to be effective in improving heart function, myocardial perfusion and metabolism. These studies indicate the BMSCs have potential as a cell therapy in some degenerative and hereditary disease.Acute tubular necrosis of the kidney is a common injury affecting renal function. It is responsible for the cause of acute renal failure in clinical cases. The current dialysis can not replace the functions of renal tubule, such as material transport, endocrine secretion, et al. The recovery of rena function depends on the regeneration of renal tubular epithelial cells. During the past several years, a great deal of attention has been focused on the plasticity of BMSCs. Ito demonstrated that BMSCs could differentiate into renal mesangial cells in anti-Thy antibody mediated glomerulonephritis. In a separate study, transplantation of whole bone marrow cells into lethally irradiated mice result in presence of bone marrow derived renal tubular epithelial cells in kidney. The animal models in which transplanted BMSCs have been found to functionally regenerate an organ are ischemia injury conditions. Ischemia reperfusion injury is characterized by alterations in cell metabolism, inflammation, free radical generation, and apoptosis that result in the detachment of renal tubular cells from the basement membrane and shedding into the urine. In our study, the bilateral renal pedicles of female BALB/C mice were clamped for 30 minutes, followed by release to allow reperfusion. Two hours later, the female mice received transplantation of bone marrow mononuclear cells isolated from homologous male mice via tail vein after 60Co sublethal dose irradiation. Fifteen days after bone marrow transplantation, PCR analysis of the male specific Sry gene confirmed the presence of male derived cells in the bone marrow of female recipients. Thirty days after BMT, Y+/CK18+ and Y+/RCA+ cells were detected in renal tubules of the recipients by serial-section analysis of fluorescence in situ DNA hybridization (FISH) and immunohistochemistry with RCA and CK18. The percentage of Y chromosome positive tubular epithelial cells in recipient mice is about 5.6% 30 days after BMT. Within a week after BMT, the fluctuation of blood urea nitrogen value of recipients mice is indistinguishable from the ischemia reperfusion mice without BMT.The results show that the ischemia reperfusion injured kidney secretes specific factors that act on the bone marrow , causing BMSCs release into the circulation and migrate to specifically the injured area. The microenvironment of injured kidney induces the BMSCs to differentiate into renal tubular epithelial cells which express CK18 or Ricinus communis (RCA) and participate in the regeneration of the injured renal tubule. Because most of the transplanted BMSCs homed to the bone marrow of the recipient mice., only a few of them are mobilized to the I/R injured area .The percentage of Y chromosome positive cells is relatively low. This perhaps is one of the reasons why the fluctuation of blood urea nitrogen value of recipient mice is indistinguishable from the control group that did not receive BMT after I/R. The study provides the conceptual basis for the therapy to stimulate the proliferation, mobilization and target the BMSCs to improve the recovery of acute renal failure.
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