(B) Direct reprogramming, numerous cell sources can theoretically be reprogrammed into iRPCs, for instance by the ectopic expression of developmental transcription factors. categories are likely to be deserving 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 around the vascular niche (vasculogenesis and angiogenesis). Multipotent stromal cells (MSC), whether derived from the bone marrow or isolated from your 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 mission to derive authentic nephron (epithelial) progenitors from differentiated pluripotent stem cells, from fetal and adult kidneys and from directly reprogrammed somatic cells. in mature B cells of mice was sufficient to cause them Fucoxanthin to dedifferentiate into uncommitted progenitors in the bone marrow and rescue T lymphopoiesis in the thymus of T-cell-deficient mice.33 However, even when considering solid organs, we can see that clinically meaningful regeneration can sometimes be achieved, even without establishing the original three-dimensional structure of the organ. If we take the pancreas and regenerative medicine for diabetic patients as an example, we can observe that individual cells are capable of sensing blood glucose levels and secreting insulin in response, such that above a critical mass of cells, diabetes can be ameliorated, regardless of the location or spatial organization of the cells. For example, in a study by Zhou et al., exocrine pancreatic cells were reprogrammed into insulin-producing cells and even though the reprogrammed cells did not organize into islet structures, they led to significant and long-lasting improvement in fasting blood glucose levels of hyperglycemic animals.34 In contrast, kidney function not only Rabbit Polyclonal to OR4C6 requires the combined action of various cell types (i.e., podocytes, parietal epithelial cells, principal cells, etc.) organized into specific segments (i.e., proximal tubule, loop of Henle, distal tubule, etc.) but also necessitates a special three-dimensional structure allowing interactions (i.e., the countercurrent mechanism) between the luminal ultra-filtrate, tubular epithelial cells and the interstitial space or peri-tubular vessels.4 The best strategy to tackle this high degree of complexity and cellular heterogeneity is probably establishment of multipotent stem/progenitor cells that could be administered into the diseased kidney, where in situ differentiation would take place, thereby replenishing the full spectrum of renal cells, leading to regeneration.4 Nonetheless, it cannot be excluded that progenitor cells with a more limited differentiation potential may also suffice as a therapeutic tool, since some pathologies are limited Fucoxanthin to specific cell types, such as podocyte loss seen in many glomerular diseases (e.g., focal segmental glomerulosclerosis4). In order to fully appreciate the development, characteristics and function of the multipotent nephron stem cells, one must first understand the processes involved in kidney development, which is the only circumstance of de novo formation of nephrons in humans. Kidney Organogenesis as a Model for Understanding Neo-Nephrogenesis The metanephros, the mature mammalian kidney, is formed via reciprocal Fucoxanthin interactions between two intermediate mesoderm (IM)-derived precursor tissues, the metanephric mesenchyme (MM) and ureteric bud (UB), a derivative of the Wolffian duct.35,36 This complex process is summarized in Figure 1. Early in the process, a fraction of MM cells, called the cap mesenchyme (CM), located just adjacent to the UB tip, condense and maintain themselves at the tips of the branching UB while, at the same time, giving off cells that differentiate into mature nephrons.37 Recent studies13C16,38C41 have established that these CM cells are able to self-renew and differentiate into different types of nephron epithelia, thereby fitting within the criteria of renal stem cells. Prior to their induction, CM cells express a unique combination of transcription factors, including the paralogs, and has recently been shown to.
