Production and Characterization of Immortal Human Neural Stem Cell Line with Multipotent Differentiation Property

Kim, Seung Up; Nagai, Atsushi; Nakagawa, Eiji; Choi, Hyun B.; Bang, Jung Hee; Lee, Hong J.; Lee, Myung A.; Lee, Yong B.; Park, In H.

doi:10.1007/978-1-59745-133-8_10

Cited by 73 publications

(68 citation statements)

References 36 publications

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“…Human NSCs (HB1.F3) were derived from a human fetal brain (ventricular zone) at 15 wk of gestation with an amphotropic, replication-incompetent retroviral vector containing v-myc (21)(22)(23)(24). This is a well-established and well-characterized NSC line, which is multipotent, migratory, and nontumorigenic in vivo.…”

Section: Methodsmentioning

confidence: 99%

Targeting Rat Brainstem Glioma Using Human Neural Stem Cells and Human Mesenchymal Stem Cells

Lee

Ahn

Kim

et al. 2009

Clinical Cancer Research

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109

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Purpose: Brainstem gliomas are usually inoperable and have a dismal prognosis.Based on the robust tropisms of neural stem cells (NSC) and mesenchymal stem cells (MSC) to brain tumors, we compared the tumor-tropic migratory capacities of these stem cells and evaluated the therapeutic potential of genetically engineered human NSCs encoding cytosine deaminase (CD) and IFNβ against brainstem gliomas. Experimental Design: The directed migratory capacities of NSCs and MSCs to brainstem glioma (F98) were evaluated both in vitro and in vivo. The human NSCs (HB1. F3) and various human MSCs, such as bone marrow-derived MSCs (HM3.B10), adipose tissue-derived MSCs, and umbilical cord blood-derived MSCs, were tested. Human fibroblast cells (HFF-1) were used as the negative control. As a proof of concept, the bioactivity of HB1.F3-CD-IFNβ was analyzed with a cell viability assay, and animals with brainstem gliomas were injected with HB1.F3-CD-IFNβ cells followed by systemic 5-fluorocytosine treatment.Results: In an in vitro modified Transwell migration assay and in vivo stem cell injection into established brainstem gliomas in rats, all the stem cells showed a significant migratory capacity compared with that of the control (P < 0.01). Histologic analysis showed a 59% reduction in tumor volume in the HB1.F3-CD-IFNβ-treated group (P < 0.05). Apoptotic cells were increased 2.33-fold in animals treated with HB1.F3-CD-IFNβ compared with the respective control groups (P < 0.01). Conclusion: The brainstem glioma-tropic migratory capacities of MSCs from various sources were similar to those of NSCs. Genetically engineered NSCs show therapeutic efficacy against brainstem gliomas.

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Section: Methodsmentioning

confidence: 99%

Targeting Rat Brainstem Glioma Using Human Neural Stem Cells and Human Mesenchymal Stem Cells

Lee

Ahn

Kim

et al. 2009

Clinical Cancer Research

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109

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“…For these studies, we used the v-myc-immortalized, human clonal HB1.F3.CD NSC line (clone 21), which is genetically and functionally stable, nontumorigenic, and minimally immunogenic [19,28,29]. HB1.F3.CD NSCs were thawed and cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% heat-inactivated fetal bovine serum and 2 mM L-glutamine for 3 days (37°C, 6% CO 2 ) in T-175 tissue culture flasks prior to adenoviral transduction.…”

Section: Neural Stem Cell Culturementioning

confidence: 99%

Neural Stem Cell-Mediated Delivery of Irinotecan-Activating Carboxylesterases to Glioma: Implications for Clinical Use

Metz

Gutova

Lacey

et al. 2013

Stem Cells Translational Medicine

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CPT-11 (irinotecan) has been investigated as a treatment for malignant brain tumors. However, limitations of CPT-11 therapy include low levels of the drug entering brain tumor sites and systemic toxicities associated with higher doses. Neural stem cells (NSCs) offer a novel way to overcome these obstacles because of their inherent tumor tropism and ability to cross the blood-brain barrier, which enables them to selectively target brain tumor sites. Carboxylesterases (CEs) are enzymes that can convert the prodrug CPT-11 (irinotecan) to its active metabolite SN-38, a potent topoisomerase I inhibitor. We have adenovirally transduced an established clonal human NSC line (HB1.F3.CD) to express a rabbit carboxylesterase (rCE) or a modified human CE (hCE1m6), which are more effective at converting CPT-11 to SN-38 than endogenous human CE. We hypothesized that NSC-mediated CE/CPT-11 therapy would allow tumor-localized production of SN-38 and significantly increase the therapeutic efficacy of irinotecan. Here, we report that transduced NSCs transiently expressed high levels of active CE enzymes, retained their tumor-tropic properties, and mediated an increase in the cytotoxicity of CPT-11 toward glioma cells. CE-expressing NSCs (NSC.CEs), whether administered intracranially or intravenously, delivered CE to orthotopic human glioma xenografts in mice. NSCdelivered CE catalyzed conversion of CPT-11 to SN-38 locally at tumor sites. These studies demonstrate the feasibility of NSC-mediated delivery of CE to glioma and lay the foundation for translational studies of this therapeutic paradigm to improve clinical outcome and quality of life in patients with malignant brain tumors. STEM CELLS TRANSLATIONAL MEDICINE 2013;2:983-992

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“…This cell line was generated from the human fetal telencephalon with the use of a retroviral vector encoding v-myc. 11,13,29 A number of gene therapy trials have been performed to improve survival rates for patients with glioblastoma with only limited gains. Nonetheless, gene therapy will continue to be used in combination with classic treatment strategies.…”

Section: Figure 5 Neural Stem Cells (Nscs) Migration Studied By Stermentioning

confidence: 99%

Stereological Analysis on Migration of Human Neural Stem Cells in the Brain of Rats Bearing Glioma

Kim

Lee

Kim³

et al. 2010

Neurosurgery

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Production and Characterization of Immortal Human Neural Stem Cell Line with Multipotent Differentiation Property

Cited by 73 publications

References 36 publications

Targeting Rat Brainstem Glioma Using Human Neural Stem Cells and Human Mesenchymal Stem Cells

Targeting Rat Brainstem Glioma Using Human Neural Stem Cells and Human Mesenchymal Stem Cells

Neural Stem Cell-Mediated Delivery of Irinotecan-Activating Carboxylesterases to Glioma: Implications for Clinical Use

Stereological Analysis on Migration of Human Neural Stem Cells in the Brain of Rats Bearing Glioma

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