title: Early intervention for spinal cord injury with human induced pluripotent stem cells oligodendrocyte progenitors.
abstract: Induced pluripotent stem (iPS) cells are at the forefront of research in regenerative medicine and are envisaged as a source for personalized tissue repair and cell replacement therapy. Here, we demonstrate for the first time that oligodendrocyte progenitors (OPs) can be derived from iPS cells generated using either an episomal, non-integrating plasmid approach or standard integrating retroviruses that survive and differentiate into mature oligodendrocytes after early transplantation into the injured spinal cord. The efficiency of OP differentiation in all 3 lines tested ranged from 40% to 60% of total cells, comparable to those derived from human embryonic stem cells. iPS cell lines derived using episomal vectors or retroviruses generated a similar number of early neural progenitors and glial progenitors while the episomal plasmid-derived iPS line generated more OPs expressing late markers O1 and RIP. Moreover, we discovered that iPS-derived OPs (iPS-OPs) engrafted 24 hours following a moderate contusive spinal cord injury (SCI) in rats survived for approximately two months and that more than 70% of the transplanted cells differentiated into mature oligodendrocytes that expressed myelin associated proteins. Transplanted OPs resulted in a significant increase in the number of myelinated axons in animals that received a transplantation 24 h after injury. In addition, nearly a 5-fold reduction in cavity size and reduced glial scarring was seen in iPS-treated groups compared to the control group, which was injected with heat-killed iPS-OPs. Although further investigation is needed to understand the mechanisms involved, these results provide evidence that patient-specific, iPS-derived OPs can survive for three months and improve behavioral assessment (BBB) after acute transplantation into SCI. This is significant as determining the time in which stem cells are injected after SCI may influence their survival and differentiation capacity.
authors: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Singapore Institute for Neurotechnology, National University of Singapore, Singapore, Singapore; Departments of Orthopedic Surgery, Biomedical Engineering and Medicine, Division of Neurology, National University of Singapore, Singapore, Singapore.
authors: Angelo H
authors: AH
authors: All
authors: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors: Payam
authors: P
authors: Gharibani
authors: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors: Siddharth
authors: S
authors: Gupta
authors: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Singapore Institute for Neurotechnology, National University of Singapore, Singapore, Singapore.
authors: Faith A
authors: FA
authors: Bazley
authors: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors: Nikta
authors: N
authors: Pashai
authors: Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors: Bin-Kuan
authors: BK
authors: Chou
authors: Division of Hematology in Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors: Sandeep
authors: S
authors: Shah
authors: Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Division of Hematology in Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors: Linda M
authors: LM
authors: Resar
authors: Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Division of Hematology in Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors: Linzhao
authors: L
authors: Cheng
authors: Department of Cell and Developmental Biology in the School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Department of Animal Biology in the School of Veterinary Medicine; University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: John D
authors: JD
authors: Gearhart
authors: Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Obstetrics and Gynecology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Biochemistry and Molecular Biology, Unversity of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors: Candace L
authors: CL
authors: Kerr
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D061345:Early Medical Intervention; D005260:Female; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation*; D009043:Motor Activity; D009186:Myelin Sheath / Q000502:physiology; D009416:Nerve Regeneration; D058953:Neural Stem Cells / Q000637:transplantation*; D009836:Oligodendroglia / Q000502:physiology; D011917:Rats, Inbred Lew; D020127:Recovery of Function; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000628:therapy*; D016896:Treatment Outcome
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