Abstract 6: Therapeutic Angiogenesis by Human CD34+ Hematopoietic Stem Cells via Exosomes-Mediated MicroRNA Transfer

• Published in: Circulation research 2012-08, Vol.111 (suppl_1)
• Main Authors: Sahoo, Susmita, Gupta, Rajesh, Thorne, Tina, Misener, Sol, Ito, Aiko, Losordo, Douglas W, Vaughan, Douglas E
• Format: Article
• Language: English
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/res.111.suppl_1.A6

Abstract only Introduction: Locally transplanted human CD34+ hematopoietic stem cells have stimulated neovascularization in preclinical studies and have been associated with functional improvements in phase I and II clinical trials of patients with ischemic cardiovascular diseases. Recently, we have demonstrated that membrane-bound nano-vesicles called exosomes are one of the primary pro-angiogenic components of human CD34+ cell paracrine secretion that induced angiogenesis independently of the cells. Here, we hypothesize that the functional benefits associated with CD34+ cell therapy are primarily mediated by the secretion of exosomes (Exo), and that CD34+ Exo transfer pro-angiogenic microRNAs to promote angiogenesis and ischemic tissue repair. Methods and Results: Therapeutic potential of CD34+ Exo isolated from adult human peripheral blood-derived CD34+ cells was evaluated in a mouse model of hind limb ischemia (HLI). Similar to CD34+ cells, administration of CD34+ Exo from equal number of cells induced angiogenesis and tissue repair; it significantly improved perfusion (ratio: 1.01±0.04 v 0.57±0.1, P