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Successful Introduction of Human Renovascular Units into the Mammalian Kidney
- Source :
- J Am Soc Nephrol
- Publication Year :
- 2020
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2020.
-
Abstract
- Background Cell-based therapies aimed at replenishing renal parenchyma have been proposed as an approach for treating CKD. However, pathogenic mechanisms involved in CKD such as renal hypoxia result in loss of kidney function and limit engraftment and therapeutic effects of renal epithelial progenitors. Jointly administering vessel-forming cells (human mesenchymal stromal cells [MSCs] and endothelial colony-forming cells [ECFCs]) may potentially result in in vivo formation of vascular networks. Methods We administered renal tubule-forming cells derived from human adult and fetal kidneys (previously shown to exert a functional effect in CKD mice) into mice, alongside MSCs and ECFCs. We then assessed whether this would result in generation of "renovascular units" comprising both vessels and tubules with potential interaction. Results Directly injecting vessel-forming cells and renal tubule-forming cells into the subcutaneous and subrenal capsular space resulted in self-organization of donor-derived vascular networks that connected to host vasculature, alongside renal tubules comprising tubular epithelia of different nephron segments. Vessels derived from MSCs and ECFCs augmented in vivo tubulogenesis by the renal tubule-forming cells. In vitro coculture experiments showed that MSCs and ECFCs induced self-renewal and genes associated with mesenchymal-epithelial transition in renal tubule-forming cells, indicating paracrine effects. Notably, after renal injury, renal tubule-forming cells and vessel-forming cells infused into the renal artery did not penetrate the renal vascular network to generate vessels; only administering them into the kidney parenchyma resulted in similar generation of human renovascular units in vivo. Conclusions Combined cell therapy of vessel-forming cells and renal tubule-forming cells aimed at alleviating renal hypoxia and enhancing tubulogenesis holds promise as the basis for new renal regenerative therapies.
- Subjects :
- 0301 basic medicine
Kidney Glomerulus
Cell Culture Techniques
Cell- and Tissue-Based Therapy
Neovascularization, Physiologic
Nephron
Mesenchymal Stem Cell Transplantation
urologic and male genital diseases
Cell therapy
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Up Front Matters
medicine.artery
medicine
Animals
Humans
Renal artery
Progenitor cell
Renal stem cell
Cell Proliferation
Kidney
business.industry
Mesenchymal stem cell
Endothelial Cells
Cell Differentiation
Mesenchymal Stem Cells
General Medicine
Coculture Techniques
Vascular endothelial growth factor
Kidney Tubules
030104 developmental biology
medicine.anatomical_structure
chemistry
Nephrology
Cancer research
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15333450 and 10466673
- Volume :
- 31
- Database :
- OpenAIRE
- Journal :
- Journal of the American Society of Nephrology
- Accession number :
- edsair.doi.dedup.....f193df0f2156cfba26692fe834ed1668