Transplantation of Induced Pluripotent Stem Cell Derived Endothelial Cells (iPSC-ECs) and Induced Endothelial Cells (iECs) in a Murine Model of Wound Healing

Angiogenesis is a vital component of wound healing, but is impaired in patients with vascular diseases. Autologous stem cells have shown potential as pro-angiogenic therapies in pre-clinical and clinical studies. The objectives of this study were to investigate the feasibility of administering topical cell treatments to a cutaneous wound and to determine whether iPSC-ECs and iECs can accelerate wound healing via enhanced angiogenesis. IPSC-ECs and iECs were generated from human fibroblasts using established reprogramming and differentiation protocols. The cells were transduced with a firefly luciferase reporter to track survival in vivo. IPSC-ECs and iECs were tested using an established wound-healing model in male NOD-SCID mice. Wound closure, wound perfusion and cell survival were measured over a period of 10 days. On day 10, wound samples were taken for histological analyses. Wound closure was not accelerated in iPSC-EC treated wounds, although IPSC-EC wound perfusion was significantly enhanced on day 6 (Control 307 ± 14 vs. IPSC-EC 370 ± 29, p=0.03, n=9). Wound closure was enhanced in iEC treated wounds (Day 10 Control 54% ± 4% vs. iEC 62% ± 2%, p=0.04 for treatment effect, n=10), but there was no significant increase in perfusion. Cell signal was detectable in 47% of wounds for the duration of the study, but was undetectable by day 4 in the remaining 53%. Wound collagen content was not different between Control and iPSC-EC or iEC treated wounds. IPSC-ECs and iECs may promote wound healing, however challenges remain with optimising cell delivery and engraftment.