18.97.14.82
18.97.14.82
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Building blood vessels using human vasculogenic cells: clinical application
( Kyu-tae Kang )
UCI I410-ECN-0102-2021-500-000691935
This article is 4 pages or less.
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It is important to understand blood vessel regeneration process to treat ischemic diseases, to create vascularized bioengineered organs, and to find therapeutic target against vascular abnormality such as cancer. We showed previously that human endothelial colony forming cells (ECFC) combined with mesenchymal progenitor cells (MPC) form perfused human blood vessels. ECFC+MPC generate more blood vessels compared to the ECFC or MPC alone injection. Using in vivo labeling with a systemically injected mixture of human- and murine-specific lectins, we demonstrated the ability of ECFC+MPC-blood vessels to reconnect with host vessels after transplantation. ECFC+MPC-blood vessels formed in donor mouse reconnect and are perfused at day 3 after transplanted into the secondary mouse. Furthermore, we quantified the longitudinal change in perfusion volume in the same implants before and after transplantation using contrast-enhanced micro-ultrasonic imaging. Perfusion was restored at day 3 after transplantation and increased with time. These results suggest that two cell system (ECFC+MPC) can provide vascular network where blood perfusion is needed or can be applied to generate vascularized engineered constructs and organ transplantation. To prove the possibility of clinical application of two cell system, ECFC+MPC were injected into the ischemic tissues such as ischemic myocardium and ischemic hindlimb muscle. In both ischemic tissues, injected cells were retained and formed perfused blood vessels. In ischemic myocardium, ECFC+MPC injection reduced LV hypertrophy and restored cardiac function compared to PBS. Ischemic hindlimbs injected with ECFC+MPC showed faster and greater blood flow recovery compared with ECFC or MPC alone. Interestingly, systemic myeloid cell depletion with anti-Gr-1 administration blocked the improved blood flow recovery observed with ECFC+MPC in ischemic hindlimbs, suggesting that vasculogenic process of ECFC+MPC may be enhanced by coordination with host myeloid cells. Our data support that ECFC+MPC delivery could be used to reestablish blood flow and restore functions of ischemic tissues by neovascularization.

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