Ex vivo manipulation of bone marrow cells to rescue uremia-induced dysfunction for autologous therapy

Uremic toxins are known to affect the regenerative properties of tissue-resident and circulating stem cells and thus appear to be a limiting factor for autologous stem cell-based approaches for treating chronic kidney disease. The recent article by van Koppen and colleagues in Stem Cell Research & Therapy provides evidence that an ex vivo short-term pre-treatment with statins reverts the dysfunction of bone marrow stem cells isolated from rats with renal impairment. Indeed, statin pre-treated cells improved renal function in a model of established chronic kidney disease. Our commentary discusses the potential of this approach in the context of autologous cell therapy and the available knowledge on the mechanisms involved in uremia-induced stem cell dysfunction

Therapeutic effects of mesenchymal stem cells on renal ischemia-reperfusion injury: A matter of genetic transfer?

Accumulating evidence indicates that the protective effect of mesenchymal stem cells in models of tissue injury is related to the endocrine/pcrine release of factors. The delivery of growth factors, cytokines, prostaglandins, enzymes or extracellular vesicles from mesenchymal stem cells to target cells may induce cell reprogramming and de novo expression of factors involved in tissue proliferation and repair. A recent paper showed that Wharton jelly-derived mesenchymal stem cells interact with injured renal tubular epithelial cells, inducing the expression of native and foreign hepatocyte growth factor necessary for renal repair and fibrogenesis inhibition. The genetic exchange between resident and mesenchymal stem cells, probably mediated through microvesicles, therefore appears instrumental in mesenchymal stem cell therapeutic effects

Efficient stem cell isolation from under vacuum preserved tissue samples

Different approaches for the isolation of stem/progenitor cells have been reported, including stem cell selection in stringent culture conditions. We evaluated the possibility of isolating human progenitor cells from surgical specimens preserved by under vacuum sealing and cooling, a clinical practice approached by several hospitals as alternative to formalin. Renal tissue samples (n = 20) maintained under vacuum from 6 to 48 h at 4°C were used to isolate human renal CD133(+) progenitor cells. We obtained CD133(+) progenitors from unsorted cells derived from disaggregated tissues from each sample. Phenotypic characterization as well as in vitro and in vivo differentiation of the obtained CD133(+) lines showed results comparable with sorted CD133(+) cells obtained from fresh tissue. These results indicate that the process of sealing under vacuum and cooling appears as a suitable tissue treatment to isolate hypoxia resistant cells, such as human stem/progenitor cells, and that this procedure can be exploited to render the extraction of stem cells from human samples more practical and feasible

Resident Stem Cells and Renal Carcinoma

According to the cancer stem cell hypothesis tumors are maintained by a cancer stem cell population which is able to initiate and maintain tumors. Tumor-initiating stem cells display stem or progenitor cell properties such as self-renewal and capacity to re-establish tumors that recapitulate the tumor of origin. In this paper, we discuss data relative to the presence of cancer stem cells in human renal carcinoma and their possible origin from normal resident stem cells. The cancer stem cells identified in human renal carcinomas are not derived from the normal CD133+ progenitors of the kidney, but rather from a more undifferentiated population that retains a mesenchymal phenotype. This population is able to self-renewal, clonogenicity, and in vivo tumor initiation. Moreover, they retain pluripotent differentiation capability, as they can generate not only the epithelial component of the tumor, but also tumor endothelial cells. This suggests that renal cancer stem cells may contribute to the intratumor vasculogenesis

Extracellular vesicles in renal tissue damage and regeneration

AbstractExtracellular vesicles (EVs) appear as important actors in cell-to-cell communication. EV content is characterized by proteins and RNA species that dynamically reflect cell and tissue state. Urinary EVs in particular may act in inter-nephron communication with possible beneficial or detrimental effects. Increasing interest is addressed to the pharmacological properties of EVs as a cell-free therapy, since several of the effects crAQ/tgqcedited to stem cells have been recapitulated by administration of their EVs. Preclinical data in models of renal damage indicate a general regenerative potential of EVs derived from mesenchymal stromal cells of different sources, including bone marrow, fetal tissues, urine and kidney. In this review we will discuss the results on the effect of EVs in repair of acute and chronic renal injury, and the mechanisms involved. In addition, we will analyse the strategies for EV pharmacological applications in renal regenerative medicine and limits and benefits involved