Mixing Cells for Vascularized Kidney Regeneration

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.

Keywords: cellular therapy; iPSCs organoids; kidney regeneration; stem-cells; vascularization.

Figure 1

Overview of engraftment strategy for vascularized kidney regenerative medicine. (a) KTFCs from fetal kidney or PSC-derived kidney organoids have the capacity to differentiate into nephrons with glomerulus, proximal tubule, loop of Henle and distal tubule. (b) KTFCs from adult kidney derived from biopsies of urine samples are lineage restricted precursor cells, able to generate segment specific tubules. (c) VFCs such as endothelial cells and peritubular support cells (pericytes and mesenchymal stem cells) are added to the cell mix to support blood vessel formation. Adapted from reference [9].