VEGF released by deferoxamine preconditioned mesenchymal stem cells seeded on collagen-GAG substrates enhances neovascularization

Abstract

Hypoxia preconditioning of mesenchymal stem cells (MSCs) has been shown to promote wound healing through HIF-1α stabilization. Preconditioned MSCs can be applied to three-dimensional biomaterials to further enhance the regenerative properties. While environmentally induced hypoxia has proven difficult in clinical settings, this study compares the wound healing capabilities of adipose derived (Ad) MSCs seeded on a collagen-glycosaminoglycan (GAG) dermal substrate exposed to either environmental hypoxia or FDA approved deferoxamine mesylate (DFO) to stabilize HIF-1α for wound healing. The release of hypoxia related reparative factors by the cells on the collagen-GAG substrate was evaluated to detect if DFO produces results comparable to environmentally induced hypoxia to facilitate optimal clinical settings. VEGF release increased in samples exposed to DFO. While the SDF-1α release was lower in cells exposed to environmental hypoxia in comparison to cells cultured in DFO in vitro. The AdMSC seeded biomaterial was further evaluated in a murine model. The implants where harvested after 1 days for histological, inflammatory, and protein analysis. The application of DFO to the cells could mimic and enhance the wound healing capabilities of environmentally induced hypoxia through VEGF expression and promises a more viable option in clinical settings that is not merely restricted to the laboratory.

Decellularized Aortic Scaffold Alleviates H2O2‐Induced Inflammation and Apoptosis in CD34+ Progenitor Cells While Driving Neovasculogenesis

“…Transplanted cells depend on oxygen and nutrients provided by microvessels. Without vascularization, transplanted cells will undergo apoptosis [35]. erefore, tissue neovascularization appears extremely important to the long-term survival of the implants and seeded cells.…”

Concise Review: Optimized Strategies for Stem Cell-Based Therapy in Myocardial Repair: Clinical Translatability and Potential Limitation

“…Deferoxamine (DFO), an FDA‐approved iron chelator, can inhibit the activity of prolyl hydroxylase that is involved in HIF‐1α degradation. DFO treatment was reported to enhance the angiogenic potential of MSCs via HIF‐1α‐mediated secretion of paracrine factors such as VEGF and SDF‐1α . Carvedilol, a nonselective β‐blocker with antioxidant properties for superoxide scavenging, was reported to protect MSCs against oxidative stress‐induced cell death .…”

Affinity Effects on the Release of Non-Conventional Antifibrotics from Polymer Depots

“…Decreases oxidative stress and necrosis [16] Enhances neovascularization [17] Reduces interstitial renal fibrosis [18] Metyrapone (MTP) Inhibition of adrenal steroidgenesis PO Enhances epithelialization [19,20] Rifampicin (RIF) Antibiotic activity PO, IV Ulcer resolution [21] Immunomodulatory [22,23] Pyrvinium pamoate (PYR) Anthelmintic activity PO Wnt inhibition [24] Inhibits fibroblast survival [25]…”