Diabetic nephropathy is a common and serious complication of diabetes. Previous research has suggested that apoptosis of podocytes plays an important role its pathophysiology. Podocytes are terminally differentiated epithelial cells that are attached to the basement membrane of the glomerulus – a network of renal capillaries. These cells play an important role in maintaining the integrity of the filtration barrier as well as the structure and function of the glomerulus. Exposure to high glucose levels can lead to a reduction in podocyte number and induce apoptosis of cultured podocytes. New research published in Stem Cell Research and Therapy investigates the effect of mesenchymal stem cells (MSCs) on podocytic apoptosis and injury, finding that they can reduce apoptosis and injury to podocytes caused by high glucose, potentially offering new treatment options for diabetic nephropathy in the future.
MSCs are a group of multipotent stem cells derived from the from the the embryonic germ layer called the mesoblast. They have previously been found to have the capacity to repair damaged tissue. Transplantation of MSCs is considered safe and has been tested in clinical trials for a number of different diseases with encouraging results. Adipose tissue provides an easily obtainable source of MSCs. These human adipose-derived MSCs (hAd-MSCs) secrete a large number of protective cytokines and exhibit other characteristics of MSCs including self-renewal and differentiation into multiple cell lineages.
Lead by Xiangmei Chen of the Chinese PLA General Hospital, Beijing, China, the researchers investigated whether hAd-MSC-conditioned medium (CM) could inhibit podocytic apoptosis induced by high glucose. Using mouse podocyte clone (MPC5) cells, they established an in vitro model of podocytic apoptosis and injury induced by high glucose. The MPC5 cells were then cultured with hAd-MSC-CM, harvested from patients using lipoaspiration.
Unlike the control (CM from a human embryonic lung cell line), hAd-MSC-CM reduced podocytic apoptosis induced by high glucose in a dose-dependent manner, downregulated activated caspase-3, and also prevented the downregulation and rearrangement of synaptopodin, a podocytic cytoskeletal protein. Further experiments showing a similar protective effect of recombinant human epithelial growth factor (EGF) on podocytes, suggest that the beneficial effects of hAd-MSCs are mediated mainly via the secretion of soluble EGF.
These findings suggest a promising role of hAd-MSCs in future therapeutic strategies for the treatment of diabetic nephropathy.
Mesenchymal stem cells protect podocytes from apoptosis induced by high glucose via secretion of epithelial growth factor
Stem Cell Research & Therapy 2013, 4:103
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