Single-cell transcriptomics identifies adipose tissue CD271+ progenitors for enhanced angiogenesis in limb ischemia.
Cell Rep Med
; 4(12): 101337, 2023 12 19.
Article
em En
| MEDLINE
| ID: mdl-38118404
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.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Perfilação da Expressão Gênica
/
Angiogênese
Limite:
Humans
Idioma:
En
Revista:
Cell Rep Med
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos