Abstract
BackgroundCell therapy has been evaluated pre-clinically and clinically as a means to improve wound vascularization and healing. While translation of this approach to clinical practice ideally requires the availability of clinical grade xenobiotic-free cell preparations, studies proving the pre-clinical efficacy of the latter are mostly lacking. Here, the potential of xenobiotic-free human multipotent adult progenitor cell (XF-hMAPC®) preparations to promote vascularization was evaluated.MethodsThe potential of XF-hMAPC cells to support blood vessel formation was first scored in an in vivo Matrigel assay in mice. Next, a dose-response study was performed with XF-hMAPC cells in which they were tested for their ability to support vascularization and (epi) dermal healing in a physiologically relevant splinted wound mouse model.ResultsXF-hMAPC cells supported blood vessel formation in Matrigel by promoting the formation of mature (smooth muscle cell-coated) vessels. Furthermore, XF-hMAPC cells dose-dependently improved wound vascularization associated with increasing wound closure and re-epithelialization, granulation tissue formation, and dermal collagen organization.ConclusionsHere, we demonstrated that the administration of clinical-grade XF-hMAPC cells in mice represents an effective approach for improving wound vascularization and healing that is readily applicable for translation in humans.
Highlights
Cell therapy has been evaluated pre-clinically and clinically as a means to improve wound vascularization and healing
We demonstrate that XF-Human multipotent adult progenitor cells (hMAPCs) cells had a dose-dependent effect on multiple wound healing parameters, including wound closure, vascularization, re-epithelialization, and collagen organization
Consistent with the macroscopic observations, implants with XF-hMAPC cells implant stained with anti-human (h)CD34 in green
Summary
Cell therapy has been evaluated pre-clinically and clinically as a means to improve wound vascularization and healing. While translation of this approach to clinical practice ideally requires the availability of clinical grade xenobiotic-free cell preparations, studies proving the pre-clinical efficacy of the latter are mostly lacking. The potential of xenobiotic-free human multipotent adult progenitor cell (XF-hMAPC®) preparations to promote vascularization was evaluated. Wound healing is one of the areas of unmet clinical need for which stem cell therapy may offer a solution. Cutaneous wound healing occurs in four partially overlapping phases [2, 3]. Neutrophils, lymphocytes, macrophages, and mast cells move to the wound site to clear up damaged material and bacteria. During the proliferation or granulation tissue formation phase, a provisional collagen matrix is deposited by
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