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Single-cell transcriptomics identifies adipose tissue CD271+ progenitors for enhanced angiogenesis in limb ischemia.
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.
Afiliación
  • Inoue O; Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan; Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • Goten C; Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
  • Hashimuko D; Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
  • Yamaguchi K; Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
  • Takeda Y; Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
  • Nomura A; Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
  • Ootsuji H; Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
  • Takashima S; Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
  • Iino K; Department of Thoracic, Cardiovascular and General Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
  • Takemura H; Department of Thoracic, Cardiovascular and General Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
  • Halurkar M; Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • Lim HW; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
  • Hwa V; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Premium Research Institute for Human Medicine (WPI-PRIMe), Osaka University, Osaka, Japan; Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • Sanchez-Gurmaches J; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. Electroni
  • Usui S; Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan. Electronic address: usuiso@staff.kanazawa-u.ac.jp.
  • Takamura M; Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan. Electronic address: mtakamura@staff.kanazawa-u.ac.jp.
Cell Rep Med ; 4(12): 101337, 2023 12 19.
Article en 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 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Perfilación de la Expresión Génica / Angiogénesis Límite: Humans Idioma: En Revista: Cell Rep Med Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Perfilación de la Expresión Génica / Angiogénesis Límite: Humans Idioma: En Revista: Cell Rep Med Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos