Brewer, Rachel E., 2017-2018

Rachel E. Brewer
Rachel E.
Brewer

"Isolating a Human-derived Vessel Stem-Like Cell and Characterizing the Vascular Niche in a murine Model"

Host Mentors: Charles K.F. Chan , Michael T. Longaker
Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford Immunology
Stanford School of Medicine

Ischemic injuries including coronary and peripheral arterial clots can lead to stroke or myocardial infarction and ultimately, death of the tissue.  Attempts to re-vascularize these tissues has been an active area of study but thus far clinical trials using various cell types, or recombinant proteins have shown little efficacy.  Previously in our lab, we identified two unique populations in mice which, when combined, gave rise to de novo vessels in vivo following ischemic injury.  Here we utilize a similar, FACS based approach, to identify corresponding populations from human-derived adipose tissue.  Analogously, the human-derived populations form functional vasculature demonstrating their translational potential.  Additionally, we further characterized our previously isolated mouse populations. Colony formation assays indicated that our Tie2+PDGFRa+CD31- population gave rise to the Tie2+PDGFRa-CD31+ population, itself and a third population (Tie2+PDGFRa+CD31+).  Microarray analysis identified PDGF as a putative signaling pathway through which they communicate during neovascularization.  Local inhibition of PDGF impeded the formation of vessels following transplant.  Taken together these data demonstrate that there is likely a hierarchy of potency among these populations which is supported by signaling within their microenvironment.  Overall, a greater understanding of the niche-like interactions between the two identified populations is required to improve cell based-therapies for the treatment of arterial disease.