Bone marrow-derived cells can acquire renal stem cells properties and ameliorate ischemia-reperfusion induced acute renal injury

<p>Abstract</p> <p>Background</p> <p>Bone marrow (BM) stem cells have been reported to contribute to tissue repair after kidney injury model. However, there is no direct evidence so far that BM cells can trans-differentiate into renal stem cells.</p> <p>Methods</p> <p>To investigate whether BM stem cells contribute to repopulate the renal stem cell pool, we transplanted BM cells from transgenic mice, expressing enhanced green fluorescent protein (EGFP) into wild-type irradiated recipients. Following hematological reconstitution and ischemia-reperfusion (I/R), Sca-1 and c-Kit positive renal stem cells in kidney were evaluated by immunostaining and flow cytometry analysis. Moreover, granulocyte colony stimulating factor (G-CSF) was administrated to further explore if G-CSF can mobilize BM cells and enhance trans-differentiation efficiency of BM cells into renal stem cells.</p> <p>Results</p> <p>BM-derived cells can contribute to the Sca-1⁺ or c-Kit⁺ renal progenitor cells population, although most renal stem cells came from indigenous cells. Furthermore, G-CSF administration nearly doubled the frequency of Sca-1+ BM-derived renal stem cells and increased capillary density of I/R injured kidneys.</p> <p>Conclusions</p> <p>These findings indicate that BM derived stem cells can give rise to cells that share properties of renal resident stem cell. Moreover, G-CSF mobilization can enhance this effect.</p

Selecting the optimal cell for kidney regeneration: Fetal, adult or reprogrammed stem cells

Chronic kidney disease (CKD) is a progressive loss in renal function over a period of months or years. End-stage renal disease (ESRD) or stage 5 CKD ensues when renal function deteriorates to under 15% of the normal range. ESRD requires either dialysis or, preferentially, a kidney organ allograft, which is severely limited due to organ shortage for transplantation. To combat this situation, one needs to either increase supply of organs or decrease their demand. Two strategies therefore exist: for those that have completely lost their kidney function (ESRD), we will need to supply new kidneys. Taking into account the kidneys' extremely complex structure, this may prove to be impossible in the near future. In contrast, for those patients that are in the slow progression route from CKD to ESRD but still have functional kidneys, we might be able to halt progression by introducing stem cell therapy to diseased kidneys to rejuvenate or regenerate individual cell types. Multiple cell compartments that fall into three categories are likely to be worthy targets for cell repair: vessels, stroma (interstitium) and nephron epithelia. Different stem/progenitor cells can be linked to regeneration of specific cell types; hematopoietic progenitors and hemangioblastic cell types have specific effects on the vascular niche (vasculogenesis and angiogenesis). Multipotent stromal cells (MSC), whether derived from the bone marrow or isolated from the kidney's non-tubular compartment, may, in turn, heal nephron epithelia via paracrine mechanisms. Nevertheless, as we now know that all of the above lack nephrogenic potential, we should continue our quest to derive genuine nephron (epithelial) progenitors from differentiated pluripotent stem cells, from fetal and adult kidneys and from directly reprogrammed somatic cells

Illustration of extensive extracellular matrix at the epithelial-mesenchymal interface within the renal stem/progenitor cell niche

<p>Abstract</p> <p>Background</p> <p>Stem/progenitor cells are promising candidates to treat diseased renal parenchyma. However, implanted stem/progenitor cells are exposed to a harmful atmosphere of degenerating parenchyma. To minimize hampering effects after an implantation investigations are in progress to administer these cells within an artificial polyester interstitum supporting survival. Learning from nature the renal stem/progenitor cell niche appears as a valuable model. At this site epithelial stem/progenitor cells within the collecting duct ampulla face mesenchymal stem/progenitor cells. Both cell types do not have close contact but are separated by a wide interstitium.</p> <p>Methods</p> <p>To analyze extracellular matrix in this particular interstitium, special contrasting for transmission electron microscopy was performed. Kidneys of neonatal rabbits were fixed in solutions containing glutaraldehyde (GA) or in combination with cupromeronic blue, ruthenium red and tannic acid.</p> <p>Results</p> <p>GA revealed a basal lamina at the ampulla and a bright but inconspicuously looking interstitial space. In contrast, GA containing cupromeronic blue exhibits numerous proteoglycan braces lining from the ampulla towards the interstitial space. GA containing ruthenium red or tannic acid demonstrates clouds of extracellular matrix protruding from the basal lamina of the ampulla to the surface of mesenchymal stem/progenitor cells.</p> <p>Conclusions</p> <p>The actual data show that the interstitium between epithelial and mesenchymal stem/progenitor cells contains much more and up to date unknown extracellular matrix than earlier observed by classical GA fixation.</p