TY - JOUR
T1 - In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell-derived neural stem/progenitor cells transplantation
AU - Tanimoto, Yuji
AU - Yamasaki, Tomoteru
AU - Nagoshi, Narihito
AU - Nishiyama, Yuichiro
AU - Nori, Satoshi
AU - Nishimura, Soraya
AU - Iida, Tsuyoshi
AU - Ozaki, Masahiro
AU - Tsuji, Osahiko
AU - Ji, Bin
AU - Aoki, Ichio
AU - Jinzaki, Masahiro
AU - Matsumoto, Morio
AU - Fujibayashi, Yasuhisa
AU - Zhang, Ming Rong
AU - Nakamura, Masaya
AU - Okano, Hideyuki
N1 - Funding Information:
We thank S. Yamanaka at CiRA (Kyoto University) for the human iPSCs (253G1 and 414C2), E. Ikeda (Yamaguchi University) for the U251-MG, Dr. B. Ji (NIRS) for the anti-TSPO antibody, and Dr. R. Darnell (Rockefeller University) for the anti-Hu antibody. We are grateful for the assistance of T. Okubo, S. Ito, K. Kojima, Y. Hoshino, R. Shibata, Y. Kamata, K. Kajikawa, K. Ago, T. Kitagawa, M. Kawai, T. Shibata, S. Hashimoto, K. Yasutake, M. Akizawa, and T. Harada who are all members of the spinal cord research team at the Department of Orthopaedic Surgery/Physiology, Keio University School of Medicine, Tokyo, Japan. We are very appreciative of H. Wakizaka and Z. Yiding for animal PET imaging. We also thank N. Nitta and S. Shibata for animal MRI imaging. This work was supported by the Japan Agency for Medical Research and Development (AMED; grant no. 15bm0204001h0003 to H.O. and M.N.) and partly by a medical research grant related to traffic accidents from the General Insurance Association of Japan (grant no. 18-1-045). In addition, the devices for MRI were supported by the Center of Innovation (COI) stream program by Japan Science and Technology Agency (JST).
Funding Information:
We thank S. Yamanaka at CiRA (Kyoto University) for the human iPSCs (253G1 and 414C2), E. Ikeda (Yamaguchi University) for the U251‐MG, Dr B. Ji (NIRS) for the anti‐TSPO antibody, and Dr R. Darnell (Rockefeller University) for the anti‐Hu antibody. We are grateful for the assistance of T. Okubo, S. Ito, K. Kojima, Y. Hoshino, R. Shibata, Y. Kamata, K. Kajikawa, K. Ago, T. Kitagawa, M. Kawai, T. Shibata, S. Hashimoto, K. Yasutake, M. Akizawa, and T. Harada who are all members of the spinal cord research team at the Department of Orthopaedic Surgery/Physiology, Keio University School of Medicine, Tokyo, Japan. We are very appreciative of H. Wakizaka and Z. Yiding for animal PET imaging. We also thank N. Nitta and S. Shibata for animal MRI imaging. This work was supported by the Japan Agency for Medical Research and Development (AMED; grant no. 15bm0204001h0003 to H.O. and M.N.) and partly by a medical research grant related to traffic accidents from the General Insurance Association of Japan (grant no. 18‐1‐045). In addition, the devices for MRI were supported by the Center of Innovation (COI) stream program by Japan Science and Technology Agency (JST).
Publisher Copyright:
© 2020 The Authors. Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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.
AB - 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.
KW - PET
KW - human-induced pluripotent stem cell-derived neural stem/progenitor cells
KW - in vivo imaging
KW - spinal cord injury
KW - stem cell transplantation
UR - http://www.scopus.com/inward/record.url?scp=85078221623&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85078221623&partnerID=8YFLogxK
U2 - 10.1002/sctm.19-0150
DO - 10.1002/sctm.19-0150
M3 - Article
C2 - 31904914
AN - SCOPUS:85078221623
SN - 2157-6564
VL - 9
SP - 465
EP - 477
JO - Stem Cells Translational Medicine
JF - Stem Cells Translational Medicine
IS - 4
ER -
