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

Cell Rep Med. 2023 Dec 19;4(12):101337. doi: 10.1016/j.xcrm.2023.101337.

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 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.

Keywords: CD271; adipose tissue; cell therapy; critical limb ischemia; insulin resistance; peripheral artery disease; single-cell transcriptomics; therapeutic angiogenesis.

MeSH terms

  • Adapalene
  • Adipose Tissue
  • Angiogenesis*
  • Gene Expression Profiling*
  • Humans
  • Ischemia / genetics

Substances

  • Adapalene