In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell-derived neural stem/progenitor cells transplantation

Yuji Tanimoto, Tomoteru Yamasaki, Narihito Nagoshi, Yuichiro Nishiyama, Satoshi Nori, Soraya Nishimura, Tsuyoshi Iida, Masahiro Ozaki, Osahiko Tsuji, Bin Ji, Ichio Aoki, Masahiro Jinzaki, Morio Matsumoto, Yasuhisa Fujibayashi, Ming Rong Zhang, Masaya Nakamura, Hideyuki Okano

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Transplantation of human-induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PCs) is a promising treatment for a variety of neuropathological conditions. Although previous reports have indicated the effectiveness of hiPSC-NS/PCs transplantation into the injured spinal cord of rodents and nonhuman primates, long-term observation of hiPSC-NS/PCs post-transplantation suggested some “unsafe” differentiation-resistant properties, resulting in disordered overgrowth. These findings suggest that, even if “safe” NS/PCs are transplanted into the human central nervous system (CNS), the dynamics of cellular differentiation of stem cells should be noninvasively tracked to ensure safety. Positron emission tomography (PET) provides molecular-functional information and helps to detect specific disease conditions. The current study was conducted to visualize Nestin (an NS/PC marker)-positive undifferentiated neural cells in the CNS of immune-deficient (nonobese diabetic-severe combined immune-deficient) mice after hiPSC-NS/PCs transplantation with PET, using 18 kDa translocator protein (TSPO) ligands as labels. TSPO was recently found to be expressed in rodent NS/PCs, and its expression decreased with the progression of neuronal differentiation. We hypothesized that TSPO would also be present in hiPSC-NS/PCs and expressed strongly in residual immature neural cells after transplantation. The results showed high levels of TSPO expression in immature hiPSC-NS/PCs-derived cells, and decreased TSPO expression as neural differentiation progressed in vitro. Furthermore, PET with [18F] FEDAC (a TSPO radioligand) was able to visualize the remnant undifferentiated hiPSC-NS/PCs-derived cells consisting of TSPO and Nestin+ cells in vivo. These findings suggest that PET with [18F] FEDAC could play a key role in the safe clinical application of CNS repair in regenerative medicine.

Original languageEnglish
Pages (from-to)465-477
Number of pages13
JournalStem Cells Translational Medicine
Volume9
Issue number4
DOIs
Publication statusPublished - 2020 Apr 1

Keywords

  • PET
  • human-induced pluripotent stem cell-derived neural stem/progenitor cells
  • in vivo imaging
  • spinal cord injury
  • stem cell transplantation

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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