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[Preprint]. 2023 Feb 13:2023.02.09.527726. [Version 2] doi: 10.1101/2023.02.09.527726

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

Oto Inoue, Chiaki Goten, Daiki Hashimuko, Kosei Yamaguchi, Yusuke Takeda, Ayano Nomura, Hiroshi Ootsuji, Shinichiro Takashima, Kenji Iino, Hirofumi Takemura, Manasi Halurkar, Hee-Woong Lim, Vivian Hwa, Joan Sanchez-Gurmaches, Soichiro Usui, Masayuki Takamura
PMCID: PMC9980009  PMID: 36865239

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 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.

HIGHLIGHTS

  • Adipose tissue stromal cells have a distinct angiogenic gene profile among human cell sources.

  • CD271 + progenitors in adipose tissue have a prominent angiogenic gene profile.

  • CD271 + progenitors show superior therapeutic capacities for limb ischemia.

  • CD271 + progenitors are reduced and functionally impaired in insulin resistant donors.

GRAPHICAL ABSTRACT

Full Text Availability

The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server.


Articles from bioRxiv are provided here courtesy of Cold Spring Harbor Laboratory Preprints

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