Premium
Evaluation of human fetal neural stem/progenitor cells as a source for cell replacement therapy for neurological disorders: Properties and tumorigenicity after long‐term in vitro maintenance
Author(s) -
Ogawa Daisuke,
Okada Yohei,
Nakamura Masaya,
Kanemura Yonehiro,
Okano Hirotaka James,
Matsuzaki Yumi,
Shimazaki Takuya,
Ito Mamoru,
Ikeda Eiji,
Tamiya Takashi,
Nagao Seigo,
Okano Hideyuki
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21843
Subject(s) - progenitor cell , in vivo , stem cell , transplantation , neural stem cell , in vitro , bioluminescence imaging , biology , cell therapy , cancer research , microbiology and biotechnology , cell culture , andrology , neuroscience , medicine , biochemistry , transfection , genetics , luciferase
It is expected that human neural stem/progenitor cells (hNS/PCs) will some day be used in cell replacement therapies. However, their availability is limited because of ethical issues, so they have to be expanded to obtain sufficient amounts for clinical application. Moreover, in‐vitro‐maintained hNS/PCs may have a potential for tumorigenicity that could be manifested after transplantation in vivo. In the present study, we demonstrate the in vitro and in vivo properties of long‐term‐expanded hNS/PCs, including a 6‐month bioluminescence imaging (BLI) study of their in vivo tumorigenicity. hNS/PCs cultured for approximately 250 days in vitro (hNS/PCs‐250) exhibited a higher growth rate and greater neurogenic potential than those cultured for approximately 500 days in vitro (hNS/PCs‐500), which showed greater gliogenic potential. In vivo, both hNS/PCs‐250 and ‐500 differentiated into neurons and astrocytes 4 weeks after being transplanted into the striatum of immunodeficient mice, and hNS/PCs‐250 exhibited better survival than hNS/PCs‐500 at this time point. We also found that the grafted hNS/PCs‐250 survived stably and differentiated properly into neurons and astrocytes even 6 months after the surgery. Moreover, during the 6‐month observation period by BLI, we did not detect any evidence of rapid tumorigenic growth of the grafted hNS/PCs, and neither PCNA/Ki67‐positive proliferating cells nor significant malignant invasive features were detected histologically. These findings support the idea that hNS/PCs may represent a nontumorigenic, safe, and appropriate cell source for regenerative therapies for neurological disorders. © 2008 Wiley‐Liss, Inc.