Single-cell transcriptomics identifies adipose tissue CD271 + progenitors for enhanced angiogenesis in limb ischemia

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 identify CD271 progenitors specifically from subcutaneou...

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Bibliographic Details
Published in:Cell reports. Medicine 2023-12, Vol.4 (12), p.101337-101337, Article 101337
Main Authors: Inoue, Oto, Goten, Chiaki, Hashimuko, Daiki, Yamaguchi, Kosei, Takeda, Yusuke, Nomura, Ayano, Ootsuji, Hiroshi, Takashima, Shinichiro, Iino, Kenji, Takemura, Hirofumi, Halurkar, Manasi, Lim, Hee-Woong, Hwa, Vivian, Sanchez-Gurmaches, Joan, Usui, Soichiro, Takamura, Masayuki
Format: Article
Language:English
Subjects:
Adapalene
Adipose Tissue
Angiogenesis
Gene Expression Profiling
Humans
Ischemia - genetics
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Summary: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 identify 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 demonstrate 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 are 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.
ISSN:2666-3791
2666-3791
DOI:10.1016/j.xcrm.2023.101337