期刊
STEM CELL RESEARCH
卷 19, 期 -, 页码 55-64出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.scr.2017.01.004
关键词
iPSC; Spinal cord injury; Neural repair; Neuroprotection
资金
- Department of Neurosurgery, the University of Texas Health Science Center at Houston
- Memorial Hermann Foundation-Staman Ogilvie Fund
- Bentsen Stroke Center
- TIRR Foundation through Mission Connect [014-115]
- Craig H. Neilsen Foundation [338617]
- NIH [R01 NS061975]
- NSF [CBET1134449]
As a potentially unlimited autologous cell source, patient induced pluripotent stemcells (iPSCs) provide great capability for tissue regeneration, particularly in spinal cord injury (SCI). However, despite significant progress made in translation of iPSC-derived neural progenitor cells (NPCs) to clinical settings, a few hurdles remain. Among them, non-invasive approach to obtain source cells in a timely manner, safer integration-free delivery of reprogramming factors, and purification of NPCs before transplantation are top priorities to overcome. In this study, we developed a safe and cost-effective pipeline to generate clinically relevant NPCs. We first isolated cells frompatients' urine and reprogrammed them into iPSCs by non-integrating Sendai viral vectors, and carried out experiments on neural differentiation. NPCs were purified by A2B5, an antibody specifically recognizing a glycoganglioside on the cell surface of neural lineage cells, via fluorescence activated cell sorting. Upon further in vitro induction, NPCs were able to give rise to neurons, oligodendrocytes and astrocytes. To test the functionality of the A2B5 + NPCs, we grafted them into the contused mouse thoracic spinal cord. Eight weeks after transplantation, the grafted cells survived, integrated into the injured spinal cord, and differentiated into neurons and glia. Our specific focus on cell source, reprogramming, differentiation and purification method purposely addresses timing and safety issues of transplantation to SCI models. It is our belief that this work takes one step closer on using human iPSC derivatives to SCI clinical settings. (C) 2017 The Authors. Published by Elsevier B.V.
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