Human CD133+ Renal Progenitor Cells Induce Erythropoietin Production and Limit Fibrosis After Acute Tubular Injury

Abstract

Persistent alterations of the renal tissue due to maladaptive repair characterize the outcome of acute kidney injury (AKI), despite a clinical recovery. Acute damage may also limit the renal production of erythropoietin, with impairment of the hemopoietic response to ischemia and possible lack of its reno-protective action. We aimed to evaluate the effect of a cell therapy using human CD133+ renal progenitor cells on maladaptive repair and fibrosis following AKI in a model of glycerol-induced rhabdomyolysis. In parallel, we evaluated the effect of CD133+ cells on erythropoietin production. Administration of CD133+ cells promoted the restoration of the renal tissue, limiting the presence of markers of injury and pro-inflammatory molecules. In addition, it promoted angiogenesis and protected against fibrosis up to day 60. No effect of dermal fibroblasts was observed. Treatment with CD133+ cells, but not with PBS or fibroblasts, limited anemia and increased erythropoietin levels both in renal tissue and in circulation. Finally, CD133+ cells contributed to the local production of erythropoietin, as observed by detection of circulating human erythropoietin. CD133+ cells appear therefore an effective source for cell repair, able to restore renal functions, including erythropoietin release, and to limit long term maldifferentiation and fibrosis.

Disturbances in angiogenesis and vascular maturation in the skin are associated with diabetic kidney disease in type 1 diabetes

“…CD133+ progenitor cells were used for the treatment in an animal model of acute kidney injury (AKI). CD133+ cells promoted the restoration of the renal tissue, limiting the presence of markers of injury and pro-inflammatory molecules, promoted angiogenesis and protected against fibrosis [18]. Moreover, in the previous study we have found a negative correlation between CD31 MVD and skin auto fluorescence (AF) [19].…”

“…The study group consisted of 148 (87 men) consecutive patients with type 1 diabetes, median age (IQR) of 41 (31-49) years and diabetes duration of 21 (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) years. The patients were under the care of the Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences.…”

Prominin-1-Specific Binding Peptide-Modified Apoferritin Nanoparticle Carrying Irinotecan as a Novel Radiosensitizer for Colorectal Cancer Stem-Like Cells

“…PROM1 is a stem cell marker for normal tissues, including bone marrow, brain, kidney, prostate, pancreas, and skin tissues . PROM1‐positive cells in the kidney are regarded as renal progenitor cells . The high IRI levels in the kidney after PROM1‐NP treatment might be explained by the moderate PROM1 expression in the kidneys, indicating the mechanism of drug elimination by the kidneys and highlighting the potential nephrotoxicity.…”

Kidney Cells Regeneration: Dedifferentiation of Tubular Epithelium, Resident Stem Cells and Possible Niches for Renal Progenitors

“…However, not in all studies the real improvement of the organ functions was achieved [33]. It is known that cell therapy with resident kidney progenitor cells reduces the activation of apoptosis and inflammation [126], improves angiogenesis [127], reduces fibrosis [128,129], and even increases animal survival after kidney injury [130].…”