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

Abstract

A kidney is an organ with relatively low basal cellular regenerative potential. However, renal cells have a pronounced ability to proliferate after injury, which undermines that the kidney cells are able to regenerate under induced conditions. The majority of studies explain yielded regeneration either by the dedifferentiation of the mature tubular epithelium or by the presence of a resident pool of progenitor cells in the kidney tissue. Whether cells responsible for the regeneration of the kidney initially have progenitor properties or if they obtain a “progenitor phenotype” during dedifferentiation after an injury, still stays the open question. The major stumbling block in resolving the issue is the lack of specific methods for distinguishing between dedifferentiated cells and resident progenitor cells. Transgenic animals, single-cell transcriptomics, and other recent approaches could be powerful tools to solve this problem. This review examines the main mechanisms of kidney regeneration: dedifferentiation of epithelial cells and activation of progenitor cells with special attention to potential niches of kidney progenitor cells. We attempted to give a detailed description of the most controversial topics in this field and ways to resolve these issues.

Kidney Inflammation, Injury and Regeneration

“…This Special Issue covers research articles that investigated the molecular mechanisms of inflammation [1][2][3] and injury [4,5] during different renal pathologies and renal regeneration [6], diagnostics using new biomarkers [7][8][9], and the effects of different stimuli like medication or bacterial components on isolated renal cells or in vivo models [10][11][12], all of which were summarized in a very simplified manner. Furthermore, this Special Issue contains important reviews that dealt with the current knowledge of cell death and regeneration [13,14], inflammation [15][16][17][18], and the molecular mechanisms of kidney diseases [19][20][21][22]. In addition, the potential of cell-based therapy approaches that use mesenchymal stromal/stem cells (MSCs) or their derivates is summarized [23][24][25].…”

“…Others discussed the molecular basis of injury and repair in distinct cell types of the kidney during arterial hypertension [21]. In this context, the main mechanisms of kidney regeneration, while focusing on epithelial cell dedifferentiation and the activation of progenitor cells with special attention on the potential niches of kidney progenitor cells, were also lighted [13]. Three reviews by Yun [25], Bochon [23] and Lee [24] summarized the therapeutic potential and efficacy of MSCs, which are primarily associated with their capability to inhibit inflammation and initiate renal regeneration.…”

Regional Responses in Radiation-Induced Normal Tissue Damage

“…Several organs would be of particular interest to study. The kidney consists of structurally separated tissues with several potential stem and progenitor cell niches [171]. Radiotherapy treatment in the kidney can result in late complications, such as nephropathy [172].…”

Differentiating Induced Pluripotent Stem Cells into Renal Cells: A New Approach to Treat Kidney Diseases

“…Adult renal tissue has a limited regeneration capacity after an injury [18]. In this context, there is growing interest in the study of regenerative cell therapy in kidney diseases, especially those involving the use of renal cells derived from induced pluripotent stem cells (iPSC).…”