Long-term survival and differentiation of human neural stem cells in nonhuman primate brain with no immunosuppression.
Cellular fate of human neural stem cells (hNSCs) transplanted in the brain of nonhuman primates (NHPs) with no immunosuppression was determined at 22 and 24 months posttransplantation (PTx) regarding survival, differentiation, and tumorigenesis. Survival of hNSCs labeled with magnetic nanoparticles was successfully detected around injection sites in the brain at 22 months PTx by MRI. Histological examination of brain sections with H&E and Prussian blue staining at 24 months revealed that most of the grafted hNSCs were found located along the injection tract. Grafted hNSCs were found to differentiate into neurons at 24 months PTx. In addition, none of the grafted hNSCs were bromodeoxyuridine positive in the monkey brain, indicating that hNSCs did not replicate in the NHP brain and did not cause tumor formation. This study serves as a proof of principle and provides evidence that hNSCs transplanted in NHP brain could survive and differentiate into neurons in the absence of immunosuppression. It also serves as a preliminary study in our scheduled preclinical studies of hNSC transplantation in NHP stroke models.
National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Korea.
Sang-Rae
SR
Lee
Hong J
HJ
Lee
Sang-Hoon
SH
Cha
Kang-Jin
KJ
Jeong
Youngjeon
Y
Lee
Chang-Yeop
CY
Jeon
Kyung Sik
KS
Yi
Inja
I
Lim
Zang-Hee
ZH
Cho
Kyu-Tae
KT
Chang
Seung U
SU
Kim
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D002454:Cell Differentiation; D002460:Cell Line; D005260:Female; D006801:Humans; D007621:Karyotyping; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry; D058953:Neural Stem Cells / Q000737:chemistry / Q000166:cytology / Q000637:transplantation*; D009474:Neurons / Q000166:cytology; D011859:Radiography; D012822:Silicon Dioxide / Q000737:chemistry; D014183:Transplantation, Heterologous
D058185:Magnetite Nanoparticles; D012822:Silicon Dioxide