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...

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Main Authors: Sang-Rae Lee, Hong J. Lee, Sang-Hoon Cha, Kang-Jin Jeong, Youngjeon Lee, Chang-Yeop Jeon, Kyung Sik Yi, Inja Lim, Zang-Hee Cho, Kyu-Tae Chang Ph.D., Seung U. Kim M.D., Ph.D.
Format: Article
Language:English
Published: SAGE Publishing 2015-02-01
Series:Cell Transplantation
Online Access:https://doi.org/10.3727/096368914X678526
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spelling doaj-ca651faffcb54143aa3f1db673be67402020-11-25T03:17:37ZengSAGE PublishingCell Transplantation0963-68971555-38922015-02-012410.3727/096368914X678526Long-Term Survival and Differentiation of Human Neural Stem Cells in Nonhuman Primate Brain with no ImmunosuppressionSang-Rae Lee0Hong J. Lee1Sang-Hoon Cha2Kang-Jin Jeong3Youngjeon Lee4Chang-Yeop Jeon5Kyung Sik Yi6Inja Lim7Zang-Hee Cho8Kyu-Tae Chang Ph.D.9Seung U. Kim M.D., Ph.D.10 National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Korea Medical Research Institute, Chung-Ang University College of Medicine, Seoul, Korea Department of Radiology, Chungbuk National University College of Medicine, Cheongju, Korea National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Korea National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Korea National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Korea Department of Radiology, Chungbuk National University College of Medicine, Cheongju, Korea Departmentof Physiology, Chung-Ang University College of Medicine, Seoul, Korea Neuroscience Research Institute, Gachon University of Medicine and Science, Inchon, Korea National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Korea Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, BC, CanadaCellular 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.https://doi.org/10.3727/096368914X678526
collection DOAJ
language English
format Article
sources DOAJ
author Sang-Rae Lee
Hong J. Lee
Sang-Hoon Cha
Kang-Jin Jeong
Youngjeon Lee
Chang-Yeop Jeon
Kyung Sik Yi
Inja Lim
Zang-Hee Cho
Kyu-Tae Chang Ph.D.
Seung U. Kim M.D., Ph.D.
spellingShingle Sang-Rae Lee
Hong J. Lee
Sang-Hoon Cha
Kang-Jin Jeong
Youngjeon Lee
Chang-Yeop Jeon
Kyung Sik Yi
Inja Lim
Zang-Hee Cho
Kyu-Tae Chang Ph.D.
Seung U. Kim M.D., Ph.D.
Long-Term Survival and Differentiation of Human Neural Stem Cells in Nonhuman Primate Brain with no Immunosuppression
Cell Transplantation
author_facet Sang-Rae Lee
Hong J. Lee
Sang-Hoon Cha
Kang-Jin Jeong
Youngjeon Lee
Chang-Yeop Jeon
Kyung Sik Yi
Inja Lim
Zang-Hee Cho
Kyu-Tae Chang Ph.D.
Seung U. Kim M.D., Ph.D.
author_sort Sang-Rae Lee
title Long-Term Survival and Differentiation of Human Neural Stem Cells in Nonhuman Primate Brain with no Immunosuppression
title_short Long-Term Survival and Differentiation of Human Neural Stem Cells in Nonhuman Primate Brain with no Immunosuppression
title_full Long-Term Survival and Differentiation of Human Neural Stem Cells in Nonhuman Primate Brain with no Immunosuppression
title_fullStr Long-Term Survival and Differentiation of Human Neural Stem Cells in Nonhuman Primate Brain with no Immunosuppression
title_full_unstemmed Long-Term Survival and Differentiation of Human Neural Stem Cells in Nonhuman Primate Brain with no Immunosuppression
title_sort long-term survival and differentiation of human neural stem cells in nonhuman primate brain with no immunosuppression
publisher SAGE Publishing
series Cell Transplantation
issn 0963-6897
1555-3892
publishDate 2015-02-01
description 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.
url https://doi.org/10.3727/096368914X678526
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