Abstract
The worldwide rise in prevalence of chronic kidney disease (CKD) demands innovative bio-medical solutions for millions of kidney patients. Kidney regenerative medicine aims to replenish tissue which is lost due to a common pathological pathway of fibrosis/inflammation and rejuvenate remaining tissue to maintain sufficient kidney function. To this end, cellular therapy strategies devised so far utilize kidney tissue-forming cells (KTFCs) from various cell sources, fetal, adult, and pluripotent stem-cells (PSCs). However, to increase engraftment and potency of the transplanted cells in a harsh hypoxic diseased environment, it is of importance to co-transplant KTFCs with vessel forming cells (VFCs). VFCs, consisting of endothelial cells (ECs) and mesenchymal stem-cells (MSCs), synergize to generate stable blood vessels, facilitating the vascularization of self-organizing KTFCs into renovascular units. In this paper, we review the different sources of KTFCs and VFCs which can be mixed, and report recent advances made in the field of kidney regeneration with emphasis on generation of vascularized kidney tissue by cell transplantation.
Highlights
The aim of this review is to concisely summarize the various cell sources for kidney tissue-forming cells (KTFCs) and
It is important to note that the various KTFCs reviewed in this paper have different regenerative capacities: KTFCs from
Adult Kidney (AK) are lineage restricted and produce segment specific tubules. This constraint must be taken into consideration when planning vascularization and co-engraftment with vessel forming cells (VFCs) and supporting cells
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The second theory argues that vascularization is an intra-renal process driven by vasculo-genesis, in which resident epithelial stem cells ( known as angioblasts) differentiate and form blood vessels around the developing nephrons This process is thought to be driven by the secretion of VEGFA by the podocyte progenitors in the vascular cleft in the proximal s-shaped body [25]. Once transplanted to the kidney capsule of mice, these nSPH self-assemble into renal tubules which partially integrate to the host nephrons, attract mouse blood vessels and improve renal function in CKD mice Another exciting AK cell source which does not require an invasive procedure is the collection of urinary kidney cells found in the urine of patients. Their potential to regenerate the kidney is still investigated; they are an accessible somatic cell source for reprograming and differentiating into various tissues [39,40], including the kidney [41]
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