Early intervention for spinal cord injury with human induced pluripotent stem cells oligodendrocyte progenitors

Angelo Homayoun All, Payam Mohammadgharibani, Siddharth Gupta, Faith A. Bazley, Nikta Pashai, Bin Kuan Chou, Sandeep Shah, Linda M Smith Resar, Linzhao Cheng, John D. Gearhart, Candace L. Kerr

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere0116933
JournalPLoS One
Volume10
Issue number1
DOIs
StatePublished - Jan 30 2015

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Induced Pluripotent Stem Cells
Oligodendroglia
Stem cells
Spinal Cord Injuries
spinal cord
Retroviridae
stems
Plasmids
Transplantation
neuroglia
Neuroglia
plasmids
Rats
Animals
Repair
Myelin Proteins
induced pluripotent stem cells
oligodendroglia
Tissue
Regenerative Medicine

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Early intervention for spinal cord injury with human induced pluripotent stem cells oligodendrocyte progenitors. / All, Angelo Homayoun; Mohammadgharibani, Payam; Gupta, Siddharth; Bazley, Faith A.; Pashai, Nikta; Chou, Bin Kuan; Shah, Sandeep; Smith Resar, Linda M; Cheng, Linzhao; Gearhart, John D.; Kerr, Candace L.

In: PLoS One, Vol. 10, No. 1, e0116933, 30.01.2015.

Research output: Contribution to journalArticle

All, Angelo Homayoun ; Mohammadgharibani, Payam ; Gupta, Siddharth ; Bazley, Faith A. ; Pashai, Nikta ; Chou, Bin Kuan ; Shah, Sandeep ; Smith Resar, Linda M ; Cheng, Linzhao ; Gearhart, John D. ; Kerr, Candace L. / Early intervention for spinal cord injury with human induced pluripotent stem cells oligodendrocyte progenitors. In: PLoS One. 2015 ; Vol. 10, No. 1.
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AU - Chou, Bin Kuan

AU - Shah, Sandeep

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