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

被引：96

作者：

Lee, Do-Hun ^{[1
]}

Ahn, Yong ^{[2
]}

Kim, Seung U. ^{[4
,5
]}

Wang, Kyu-Chang ^{[1
]}

Cho, Byung-Kyu ^{[1
]}

Phi, Ji Hoon ^{[1
]}

Park, In Ho ^{[6
]}

Black, Peter M. ^{[7
]}

Carrol, Rona S. ^{[7
]}

Lee, Joonyub ^{[3
]}

Kim, Seung-Ki ^{[1
]}

机构：

[1] Seoul Natl Univ, Childrens Hosp, Div Pediat Neurosurg, Seoul 110744, South Korea

[2] Wooridul Spine Hosp, Div Neurosurg, Seoul, South Korea

[3] Seoul Natl Univ Hosp, Med Res Collaborating Ctr, Seoul 110744, South Korea

[4] Univ British Columbia, Dept Med, Div Neurol, UBC Hosp, Vancouver, BC V6T 1W5, Canada

[5] Chung Ang Univ, Coll Med, Med Res Inst, Seoul, South Korea

[6] Gachon Med Univ, Gil Hosp, Inst Regenerat Med, Inchon, South Korea

[7] Harvard Univ, Brigham & Womens Hosp, Dept Neurosurg, Sch Med, Boston, MA 02115 USA

来源：

CLINICAL CANCER RESEARCH | 2009年 / 15卷 / 15期

关键词：

UMBILICAL-CORD BLOOD; BONE-MARROW; TUMORS; TROPISM; LINE;

D O I：

10.1158/1078-0432.CCR-08-3076

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 IFN beta 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-IFN beta was analyzed with a cell viability assay, and animals with brainstem gliomas were injected with HB1.F3-CD-IFN beta 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-IFN beta-treated group (P < 0.05). Apoptotic cells were increased 2.33-fold in animals treated with HB1.F3-CD-IFN beta 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.

引用

页码：4925 / 4934

页数：10

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