Usion in mouse ischemic limbs, consistent with an attenuation of ischemic injury. In addition, iMSCs-Exo could activate angiogenesis-related molecule expression and promote HUVEC migration, proliferation, and tube formation. Conclusion: Implanted iMSCs-Exo was able to protect limbs from ischemic injury via the promotion of angiogenesis, which indicated that iMSCs-Exo may be a novel therapeutic approach in the treatment of ischemic diseases.* Correspondence: [email protected]; [email protected] Equal contributors 3 Institute of Microsurgery on Extremities, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai 200233, China 1 Department of Neurosurgery, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai 200233, China Full list of author information is available at the end of the article?2015 Hu et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Hu et al. Stem Cell Research Therapy 2015, 6:10 http://stemcellres.com/content/6/1/Page 2 ofIntroduction Stem cells are undifferentiated cells that are present in the embryonic, fetal, and adult stages of life and are defined by their ability to self-renew and differentiate into multiple lineages [1,2]. Stem cells have unique characteristics of high proliferation, specific migration, and the NIK333MedChemExpress Peretinoin potential to differentiate into many different reparative or replacement cell types. Within the last few years, the important role of stem cells in the field of cell therapy has begun to be recognized, and remarkable progress in both basic research and clinical studies has confirmed that stem cells exert positive therapeutic effects in alleviating tissue injury after ischemia, including myocardial infarction [3,4], brain ischemia [5,6], and limb ischemia [7,8]. It has been well established that bone marrow-derived mesenchymal stem cells (BMSCs) are an ideal cell source for autologous cell-based therapy because of their highly proliferative and self-regenerative capability, powerful plasticity, and low immunogenicity [9,10]. However, several disadvantages restrict BMSC clinical applications in autologous transplantation: because they are adult somatic cells, the proliferation and differentiation capability of BMSCs decrease after a number of passages in culture. In addition, their proliferation and differentiation potential decline significantly with increasing age- and aging-related disorders. In addition, only a limited number of BMSCs can be obtained initially from a single donor, limiting their further application [11,12]. Recent advances in stem cell technology PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/25432023 have enabled the generation of patient-specific induced pluripotent stem cells (iPSCs) from adult somatic cells, and these iPSCs are able to differentiate into expandable progenitor cells and mature cells [13]. iPSCs exhibit similar properties with embryonic stem cells (ESCs) in self-renewal and differentiation capacity; one distinct advantage over ESCs is that they are patient-specific and thus theoretically can overcome the need for immunos.