Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.02.09.527726v1?rss=1

Authors: Inoue, O., Goten, C., Hashimuko, D., Yamaguchi, K., Takeda, Y., Nomura, A., Ootsuji, H., Takashima, S., Iino, K., Takemura, H., Halurkar, M., Lim, H.-W., Hwa, V., Sanchez-Gurmaches, J., Usui, S., Takamura, M.

Abstract:
Therapeutic angiogenesis using mesenchymal stem/stromal cell grafts have shown modest and controversial effects in preventing amputation for patients with critical limb ischemia. Through single-cell transcriptomic analysis of human tissues, we identified CD271+ progenitors specifically from subcutaneous adipose tissue (AT) as having the most prominent pro-angiogenic gene profile distinct from other stem cell populations. AT-CD271+ progenitors demonstrated robust in vivo angiogenic capacity, over conventional adipose stromal cell grafts, characterized by long-term engraftment, augmented tissue regeneration, and significant recovery of blood flow in a xenograft model of limb ischemia. Mechanistically, the angiogenic capacity of CD271+ progenitors is dependent on functional CD271 and mTOR signaling. Notably, the number and angiogenic capacity of CD271+ progenitors was strikingly reduced in insulin resistant donors. Our study highlights the identification of AT- CD271+ progenitors with in vivo superior efficacy for limb ischemia. Furthermore, we showcase comprehensive single-cell transcriptomics strategies for identification of suitable grafts for cell therapy.

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