A Novel Approach to Enhance the Regenerative Potential of Circulating Endothelial Progenitor Cells in Patients with End-Stage Kidney Disease
journal contributionposted on 2022-05-16, 04:46 authored by A Badawi, OC Jefferson, Brooke HuuskesBrooke Huuskes, SD Ricardo, PG Kerr, CS Samuel, P Murthi
Circulating bone marrow-derived endothelial progenitor cells (EPCs) facilitate vascular repair in several organs including the kidney but are progressively diminished in end-stage kidney disease (ESKD) patients, which correlates with cardiovascular outcomes and related mortality. We thus determined if enhancing the tissue-reparative effects of human bone marrow-derived mesenchymal stromal cells (BM-MSCs) with the vasculogenic effects of recombinant human relaxin (RLX) could promote EPC proliferation and function. CD34+ EPCs were isolated from the blood of healthy and ESKD patients, cultured until late EPCs had formed, then stimulated with BM-MSC-derived condition media (CM; 25%), RLX (1 or 10 ng/mL), or both treatments combined. Whilst RLX alone stimulated EPC proliferation, capillary tube formation and wound healing in vitro, these measures were more rapidly and markedly enhanced by the combined effects of BM-MSC-derived CM and RLX in EPCs derived from both healthy and ESKD patients. These findings have important clinical implications, having identified a novel combination therapy that can restore and enhance EPC number and function in ESKD patients.
This work was supported by a National Health & Medical Research Council (NHMRC) of Australia Project Grant (GNT1156446) awarded to C.S. Samuel, S.D. Ricardo and P.G. Kerr and a Monash Biomedicine Discovery Institute Senior Research Fellowship to C.S. Samuel.
Article NumberARTN 883
Rights Statement© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Science & TechnologyLife Sciences & BiomedicineBiochemistry & Molecular BiologyMedicine, Research & ExperimentalPharmacology & PharmacyResearch & Experimental Medicineendothelial progenitor cellsend-stage kidney diseasebone-marrow derived mesenchymal stem cellsrelaxinwound healingangiogenesisregenerationMESENCHYMAL STEM-CELLSCARDIOVASCULAR MORTALITYRELAXINTHERAPIESFIBROSISDYSFUNCTIONMIGRATIONNUMBER