TY - JOUR
T1 - Long-term safety issues of iPSC-based cell therapy in a spinal cord injury model
T2 - Oncogenic transformation with epithelial-mesenchymal transition
AU - Nori, Satoshi
AU - Okada, Yohei
AU - Nishimura, Soraya
AU - Sasaki, Takashi
AU - Itakura, Go
AU - Kobayashi, Yoshiomi
AU - Renault-Mihara, Francois
AU - Shimizu, Atsushi
AU - Koya, Ikuko
AU - Yoshida, Rei
AU - Kudoh, Jun
AU - Koike, Masato
AU - Uchiyama, Yasuo
AU - Ikeda, Eiji
AU - Toyama, Yoshiaki
AU - Nakamura, Masaya
AU - Okano, Hideyuki
PY - 2015/3/10
Y1 - 2015/3/10
N2 - Previously, we described the safety and therapeutic potential of neurospheres (NSs) derived from a human induced pluripotent stem cell (iPSC) clone, 201B7, in a spinal cord injury (SCI) mouse model. However, several safety issues concerning iPSC-based cell therapy remain unresolved. Here, we investigated another iPSC clone, 253G1, that we established by transducing OCT4, SOX2, and KLF4 into adult human dermal fibroblasts collected from the same donor who provided the 201B7 clone. The grafted 253G1-NSs survived, differentiated into three neural lineages, and promoted functional recovery accompanied by stimulated synapse formation 47 days after transplantation. However, long-term observation (for up to 103 days) revealed deteriorated motor function accompanied by tumor formation. The tumors consisted of Nestin+ undifferentiated neural cells and exhibited activation of the OCT4 transgene. Transcriptome analysis revealed that a heightened mesenchymal transition may have contributed to the progression of tumors derived from grafted cells.
AB - Previously, we described the safety and therapeutic potential of neurospheres (NSs) derived from a human induced pluripotent stem cell (iPSC) clone, 201B7, in a spinal cord injury (SCI) mouse model. However, several safety issues concerning iPSC-based cell therapy remain unresolved. Here, we investigated another iPSC clone, 253G1, that we established by transducing OCT4, SOX2, and KLF4 into adult human dermal fibroblasts collected from the same donor who provided the 201B7 clone. The grafted 253G1-NSs survived, differentiated into three neural lineages, and promoted functional recovery accompanied by stimulated synapse formation 47 days after transplantation. However, long-term observation (for up to 103 days) revealed deteriorated motor function accompanied by tumor formation. The tumors consisted of Nestin+ undifferentiated neural cells and exhibited activation of the OCT4 transgene. Transcriptome analysis revealed that a heightened mesenchymal transition may have contributed to the progression of tumors derived from grafted cells.
UR - http://www.scopus.com/inward/record.url?scp=84924574219&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84924574219&partnerID=8YFLogxK
U2 - 10.1016/j.stemcr.2015.01.006
DO - 10.1016/j.stemcr.2015.01.006
M3 - Article
C2 - 25684226
AN - SCOPUS:84924574219
VL - 4
SP - 360
EP - 373
JO - Stem Cell Reports
JF - Stem Cell Reports
SN - 2213-6711
IS - 3
ER -