Early intervention for spinal cord injury with human induced pluripotent stem cells oligodendrocyte progenitors
Autor: | Nikta Pashai, John D. Gearhart, Bin Kuan Chou, Linzhao Cheng, Faith A. Bazley, Payam Gharibani, Siddharth Gupta, Angelo H. All, Candace L. Kerr, Linda M.S. Resar, Sandeep N. Shah |
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Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Cell Survival
Cellular differentiation Induced Pluripotent Stem Cells lcsh:Medicine Motor Activity Biology Neural Stem Cells Early Medical Intervention medicine Animals Humans Progenitor cell Induced pluripotent stem cell lcsh:Science Cells Cultured Myelin Sheath Spinal Cord Injuries Multidisciplinary lcsh:R Cell Differentiation Recovery of Function Embryonic stem cell Axons Neural stem cell Oligodendrocyte Nerve Regeneration 3. Good health Cell biology Transplantation Oligodendroglia Treatment Outcome medicine.anatomical_structure Spinal Cord Rats Inbred Lew Immunology Female lcsh:Q Stem cell Research Article |
Zdroj: | PLoS ONE, Vol 10, Iss 1, p e0116933 (2015) PLoS ONE |
ISSN: | 1932-6203 |
Popis: | 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. |
Databáze: | OpenAIRE |
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