Allogeneic neural stem/progenitor cells derived from embryonic stem cells promote functional recovery after transplantation into injured spinal cord of nonhuman primates

Hiroki Iwai, Hiroko Shimada, Soraya Nishimura, Yoshiomi Kobayashi, Go Itakura, Keiko Hori, Keigo Hikishima, Hayao Ebise, Naoko Negishi, Shinsuke Shibata, Sonoko Habu, Yoshiaki Toyama, Masaya Nakamura, Hideyuki Okano

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Previous studies have demonstrated that neural stem/progenitor cells (NS/PCs) promote functional recovery in rodent animal models of spinal cord injury (SCI). Because distinct differences exist in the neuroanatomy and immunological responses between rodents and primates, it is critical to determine the effectiveness and safety of allografted embryonic stem cell (ESC)-derived NS/PCs (ESC-NS/PCs) in a nonhuman primate SCI model. In the present study, common marmoset ESC-NS/PCs were grafted into the lesion epicenter 14 days after contusive SCI in adult marmosets (transplantation group). In the control group, phosphate-buffered saline was injected instead of cells. In the presence of a low-dose of tacrolimus, several grafted cells survived without tumorigenicity and differentiated into neurons, astrocytes, or oligodendrocytes. Significant differences were found in the transverse areas of luxol fast blue-positive myelin sheaths, neurofilament-positive axons, corticospinal tract fibers, and platelet endothelial cell adhesion molecule-1-positive vessels at the lesion epicenter between the transplantation and control groups. Immunoelectron microscopic examination demonstrated that the grafted ESC-NS/PC-derived oligodendrocytes contributed to the remyelination of demyelinated axons. In addition, some grafted neurons formed synaptic connections with host cells, and some transplanted neurons were myelinated by host cells. Eventually, motor functional recovery significantly improved in the transplantation group compared with the control group. In addition, a mixedlymphocyte reaction assay indicated that ESC-NS/PCs modulated the allogeneic immune rejection. Taken together, our results indicate that allogeneic transplantation of ESC-NS/PCs from a nonhuman primate promoted functional recovery after SCI without tumorigenicity.

Original languageEnglish
Pages (from-to)708-719
Number of pages12
JournalStem cells translational medicine
Volume4
Issue number7
DOIs
Publication statusPublished - 2015 Jul 1

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Neural Stem Cells
Embryonic Stem Cells
Primates
Spinal Cord
Stem Cells
Transplantation
Spinal Cord Injuries
Callithrix
Oligodendroglia
Neurons
Control Groups
Axons
Rodentia
CD31 Antigens
Neuroanatomy
Pyramidal Tracts
Intermediate Filaments
Homologous Transplantation
Tacrolimus
Myelin Sheath

Keywords

  • Allograft
  • Cell transplantation
  • Embryonic stem cells
  • Neural stem cells
  • Primates
  • Spinal cord injury

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology

Cite this

Allogeneic neural stem/progenitor cells derived from embryonic stem cells promote functional recovery after transplantation into injured spinal cord of nonhuman primates. / Iwai, Hiroki; Shimada, Hiroko; Nishimura, Soraya; Kobayashi, Yoshiomi; Itakura, Go; Hori, Keiko; Hikishima, Keigo; Ebise, Hayao; Negishi, Naoko; Shibata, Shinsuke; Habu, Sonoko; Toyama, Yoshiaki; Nakamura, Masaya; Okano, Hideyuki.

In: Stem cells translational medicine, Vol. 4, No. 7, 01.07.2015, p. 708-719.

Research output: Contribution to journalArticle

Iwai, Hiroki ; Shimada, Hiroko ; Nishimura, Soraya ; Kobayashi, Yoshiomi ; Itakura, Go ; Hori, Keiko ; Hikishima, Keigo ; Ebise, Hayao ; Negishi, Naoko ; Shibata, Shinsuke ; Habu, Sonoko ; Toyama, Yoshiaki ; Nakamura, Masaya ; Okano, Hideyuki. / Allogeneic neural stem/progenitor cells derived from embryonic stem cells promote functional recovery after transplantation into injured spinal cord of nonhuman primates. In: Stem cells translational medicine. 2015 ; Vol. 4, No. 7. pp. 708-719.
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