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

Early human evidence such as case series or small samples is exploring possible benefits.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

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. 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

Evidence level

Early human evidence such as case series or small samples is exploring possible benefits.

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