Vector-Free and Transgene-Free Human iPS Cells Differentiate into Functional Neurons and Enhance Functional Recovery after Ischemic Stroke in Mice

• Type of Material: Article
• Authors: Osama Mohamad, Emory University; Danielle Drury-Stewart, Georgia Tech Institute; Mingke Song, Emory University; Ben Faulkner, Emory University; Dongdong Chen, Emory University; Shan Ping Yu, Emory University; Ling Wei, Emory University
• Language: English
• Date: 2013-05-23
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2013 Mohamad et al.
• License: Creative Commons Attribution 2.5 Generic
• Final Published Version (URL): http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0064160
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 8
• Issue: 5
• Start Page: 1
• End Page: 12
• Grant/Funding Information: This work was funded by National Institutes of Health (NIH) grants NS 045810, NS062097, NS058710, NS057255 and the American Heart Association Established Investigator Award. It was partly supported by American Heart Association pre-doctoral fellowship award (10PRE4430032). It was also supported by the NIH grant NS055077 to the ENNCF (Emory Neurology-NINDS Core Facility).
• Research Categories: Engineering, Biomedical; Health Sciences, Medicine and Surgery

Abstract

Stroke is a leading cause of human death and disability in the adult population in the United States and around the world. While stroke treatment is limited, stem cell transplantation has emerged as a promising regenerative therapy to replace or repair damaged tissues and enhance functional recovery after stroke. Recently, the creation of induced pluripotent stem (iPS) cells through reprogramming of somatic cells has revolutionized cell therapy by providing an unlimited source of autologous cells for transplantation. In addition, the creation of vector-free and transgene-free human iPS (hiPS) cells provides a new generation of stem cells with a reduced risk of tumor formation that was associated with the random integration of viral vectors seen with previous techniques. However, the potential use of these cells in the treatment of ischemic stroke has not been explored. In the present investigation, we examined the neuronal differentiation of vector-free and transgene-free hiPS cells and the transplantation of hiPS cell-derived neural progenitor cells (hiPS-NPCs) in an ischemic stroke model in mice. Vector-free hiPS cells were maintained in feeder-free and serum-free conditions and differentiated into functional neurons in vitro using a newly developed differentiation protocol. Twenty eight days after transplantation in stroke mice, hiPS-NPCs showed mature neuronal markers in vivo. No tumor formation was seen up to 12 months after transplantation. Transplantation of hiPS-NPCs restored neurovascular coupling, increased trophic support and promoted behavioral recovery after stroke. These data suggest that using vector-free and transgene-free hiPS cells in stem cell therapy are safe and efficacious in enhancing recovery after focal ischemic stroke in mice.