Abstract
BackgroundMesenchymal stem cells derived from human umbilical cord tissue, termed UCX®, have the potential to promote a full range of events leading to tissue regeneration and homeostasis. The main goal of this work was to investigate UCX® action in experimentally induced hindlimb ischemia (HLI).MethodsUCX®, obtained by using a proprietary technology developed by ECBio (Amadora, Portugal), were delivered via intramuscular injection to C57BL/6 females after unilateral HLI induction. Perfusion recovery, capillary and collateral density increase were evaluated by laser doppler, CD31 immunohistochemistry and diaphonisation, respectively. The activation state of endothelial cells (ECs) was analysed after EC isolation by laser capture microdissection microscopy followed by RNA extraction, cDNA synthesis and quantitative RT-PCR analysis. The UCX®-conditioned medium was analysed on Gallios flow cytometer. The capacity of UCX® in promoting tubulogenesis and EC migration was assessed by matrigel tubule formation and wound-healing assay, respectively.ResultsWe demonstrated that UCX® enhance angiogenesis in vitro via a paracrine effect. Importantly, after HLI induction, UCX® improve blood perfusion by stimulating angiogenesis and arteriogenesis. This is achieved through a new mechanism in which durable and simultaneous upregulation of transforming growth factor β2, angiopoietin 2, fibroblast growth factor 2, and hepatocyte growth factor, in endothelial cells is induced by UCX®.ConclusionsIn conclusion, our data demonstrate that UCX® improve the angiogenic potency of endothelial cells in the murine ischemic limb suggesting the potential of UCX® as a new therapeutic tool for critical limb ischemia.
Highlights
Mesenchymal stem cells derived from human umbilical cord tissue, termed UCX®, have the potential to promote a full range of events leading to tissue regeneration and homeostasis
As a control Human umbilical vein endothelial cells (HUVECs) were seeded in endothelial basal medium (EBM), where we do not expect to visualize capillary-like structures formed by HUVECS
With the exception of the total mesh area, all the measured parameters were significantly different between HUVECs cultured with UCX® in EBM and HUVECs cultured in EBM supplemented with fibroblast growth factor 2 (FGF-2)
Summary
Mesenchymal stem cells derived from human umbilical cord tissue, termed UCX®, have the potential to promote a full range of events leading to tissue regeneration and homeostasis. Critical limb ischemia (CLI) is a severe form of peripheral artery disease (PAD) in which patients with occlusive arterial disease of the legs experience chronic ischemic rest pain, ulcer, or gangrene [1]. In a meta-analysis of cell therapy for PAD, it was found that autologous bone marrow MSCs delivery led to improved indices of ischemia and pain-free walking [8]. UCX® cells are advantageous in comparison to other sources due to the absence of invasiveness in their collection process, their faster self-renewal, higher cell yield and being more potent modulators of the immune system than bone marrow MSCs, making them more attractive for allogeneic cellular therapies
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