title: Human neural progenitors derived from integration-free iPSCs for SCI therapy.
abstract: As a potentially unlimited autologous cell source, patient induced pluripotent stem cells (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 from patients' 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.
authors.affiliation: Department of Neurosurgery, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX, USA; Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX, USA; The Senator Lloyd & B.A. Bentsen Center for Stroke Research, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX, USA. Electronic address: ying.liu@uth.tmc.edu.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX, USA; Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Yiyan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Neurosurgery, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX, USA; Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Shenglan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX, USA; Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Haipeng
authors.initials: H
authors.lastname: Xue
authors.affiliation: Department of Neurosurgery, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Schmitt
authors.affiliation: Department of Neurosurgery, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Georgene W
authors.initials: GW
authors.lastname: Hergenroeder
authors.affiliation: Department of Neurosurgery, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX, USA; Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX, USA; The Senator Lloyd & B.A. Bentsen Center for Stroke Research, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Jiaqian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest Health Sciences, 391 Technology Way, Winston-Salem, NC 27101, USA.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX, USA; Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Dong H
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Neurosurgery, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX, USA; Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX, USA; The Senator Lloyd & B.A. Bentsen Center for Stroke Research, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX, USA. Electronic address: qi-lin.cao@uth.tmc.edu.
authors.forename: Qilin
authors.initials: Q
authors.lastname: Cao
mesh_terms: D050156:Adipogenesis; D000328:Adult; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D059785:Karyotype; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D058953:Neural Stem Cells / Q000166:cytology* / Q000637:transplantation; D055495:Neurogenesis; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D029082:Sendai virus / Q000235:genetics; D013119:Spinal Cord Injuries / Q000473:pathology / Q000628:therapy*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014556:Urine / Q000166:cytology
chemical_list: D014157:Transcription Factors
keywords: Neural repair; Neuroprotection; Spinal cord injury; iPSC