Paracrine Proangiogenic Function of Human Bone Marrow-Derived Mesenchymal Stem Cells Is Not Affected by Chronic Kidney Disease

Abstract

Background. Cell-based therapies are being developed to meet the need for curative therapy in chronic kidney disease (CKD). Bone marrow- (BM-) derived mesenchymal stromal cells (MSCs) enhance tissue repair and induce neoangiogenesis through paracrine action of secreted proteins and extracellular vesicles (EVs). Administration of allogeneic BM MSCs is less desirable in a patient population likely to require a kidney transplant, but potency of autologous MSCs should be confirmed, given previous indications that CKD-induced dysfunction is present. While the immunomodulatory capacity of CKD BM MSCs has been established, it is unknown whether CKD affects wound healing and angiogenic potential of MSC-derived CM and EVs. Methods. MSCs were cultured from BM obtained from kidney transplant recipients (N=15) or kidney donors (N=17). Passage 3 BM MSCs and BM MSC-conditioned medium (CM) were used for experiments. EVs were isolated from CM by differential ultracentrifugation. BM MSC differentiation capacity, proliferation, and senescence-associated β-galactosidase activity was assessed. In vitro promigratory and proangiogenic capacity of BM MSC-derived CM and EVs was assessed using an in vitro scratch wound assay and Matrigel angiogenesis assay. Results. Healthy and CKD BM MSCs exhibited similar differentiation capacity, proliferation, and senescence-associated β-galactosidase activity. Scratch wound migration was not significantly different between healthy and CKD MSCs (P=0.18). Healthy and CKD BM MSC-derived CM induced similar tubule formation (P=0.21). There was also no difference in paracrine regenerative function of EVs (scratch wound: P=0.6; tubulogenesis: P=0.46). Conclusions. Our results indicate that MSCs have an intrinsic capacity to produce proangiogenic paracrine factors, including EVs, which is not affected by donor health status regarding CKD. This suggests that autologous MSC-based therapy is a viable option in CKD.

Comparative analysis of mouse bone marrow and adipose tissue mesenchymal stem cells for critical limb ischemia cell therapy

“…The intramuscular (IM) injection of MSCs in animals with CLI indicated zonal angiogenesis and improved blood flow via paracrine support of injured cells and a process of local progenitor cell differentiation, and also the regulation of angiogenic factors secretion. Furthermore, MSCs involved in the restoration of vascular integrity and neovascularization after injury via direct differentiation into blood vessel cells and also upregulate proangiogenic factors expression [28,29].…”

Clinical Efficacy and Safety of Mesenchymal Stem Cells for Systemic Lupus Erythematosus

“…Quimby et al [14] conducted a study in cats with chronic kidney disease and reported that administration of MSCs was not associated with significant improvement in renal function. van Rhijn-Brouwer et al [15] conducted a study in kidney transplant recipients and showed that MSCs have an intrinsic capacity to produce proangiogenic paracrine factors, including extracellular vesicles (EVs), which suggested that autologous MSC-based therapy is a viable option in the therapy of chronic kidney disease. Song et al [16] reported that MSC treatment can attenuate renal interstitial fibrosis possibly through inhibition of EMT and the inflammatory response via the TGF-β1 signalling pathway.…”

The Multi-Therapeutic Role of MSCs in Diabetic Nephropathy

“…Exosomal miR-16-5p from human urine-derived stem cells had been reported to alleviate DN via increasing podocyte viability and decreasing the rate of apoptosis. Overexpressed miR-16-5p in human urine stem cells significantly improved proteinuria as well as kidney function index (96). All this research concluded that miRNA could be adjusted to control the DN condition.…”

“…Another researcher investigated the pro-angiogenesis function of exosomes from MSCs. They repeatedly demonstrated the pro-angiogenesis function of MSCs-conditioned medium and identified that this potential was mediated by exosomes ( 97 ). Similarly, urine stem cell-derived exosomes contained increased VEGF, TGF-β, and angiogenin, which were reported to be involved in angiogenesis and cell survival ( 98 ).…”