Li SC, Kabeer MH, Vu LT, Keschrumrus V, Yin HZ, Dethlefs BA, Zhong JF, Weiss JH, Loudon WG. Training stem cells for treatment of malignant brain tumors. World J Stem Cells 2014; 6(4): 432-440 [PMID: 25258664 DOI: 10.4252/wjsc.v6.i4.432]
Corresponding Author of This Article
Shengwen Calvin Li, PhD, Principal Investigator/Head, Neuro-Oncology and Stem Cell Research Laboratory, Center for Neuroscience Research, Children’s Hospital of Orange County, University of California-Irvine, 1201-D W. La Veta Avenue, Orange, CA 92868, United States. shengwel@uci.edu
Research Domain of This Article
Oncology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Stem Cells. Sep 26, 2014; 6(4): 432-440 Published online Sep 26, 2014. doi: 10.4252/wjsc.v6.i4.432
Training stem cells for treatment of malignant brain tumors
Shengwen Calvin Li, Mustafa H Kabeer, Long T Vu, Vic Keschrumrus, Hong Zhen Yin, Brent A Dethlefs, Jiang F Zhong, John H Weiss, William G Loudon
Shengwen Calvin Li, Mustafa H Kabeer, Long T Vu, Vic Keschrumrus, Brent A Dethlefs, William G Loudon, Neuro-Oncology and Stem Cell Research Laboratory, Center for Neuroscience Research, Children’s Hospital of Orange County, University of California-Irvine, Orange, CA 92868, United States
Shengwen Calvin Li, Hong Zhen Yin, John H Weiss, Department of Neurology, University of California Irvine, Orange, CA 92862, United States
Jiang F Zhong, Department of Pathology, University of Southern California, Los Angeles, CA 90033, United States
Author contributions: Li SC conceived the project, performed the cell culture and human ETG culture and wrote the article; Vu LT, Keschrumrus V, Yin HZ and Weiss JH helped make engineered tissue graft; Vu LT did the heat maps; Zhong JF helped microarrays experiments; Loudon WG was for MRI, CED and tumor surgery; Kabeer MH, Dethlefs BA, Zhong JF, Weiss JH and Loudon WG commented on the draft and revision; all authors approved the final article.
Supported by The CHOC Children’s Foundation, CHOC Neuroscience Institute, CHOC Research Institute, The Austin Ford Tribute and Keck Foundation; by The United States National Institutes of Health, 1R01CA164509-01; and The United States National Science Foundation, CHE-1213161
Correspondence to: Shengwen Calvin Li, PhD, Principal Investigator/Head, Neuro-Oncology and Stem Cell Research Laboratory, Center for Neuroscience Research, Children’s Hospital of Orange County, University of California-Irvine, 1201-D W. La Veta Avenue, Orange, CA 92868, United States. shengwel@uci.edu
Telephone: +1-714-5094964 Fax: +1-714-5164318
Received: May 28, 2014 Revised: August 9, 2014 Accepted: August 30, 2014 Published online: September 26, 2014 Processing time: 120 Days and 4.7 Hours
Abstract
The treatment of malignant brain tumors remains a challenge. Stem cell technology has been applied in the treatment of brain tumors largely because of the ability of some stem cells to infiltrate into regions within the brain where tumor cells migrate as shown in preclinical studies. However, not all of these efforts can translate in the effective treatment that improves the quality of life for patients. Here, we perform a literature review to identify the problems in the field. Given the lack of efficacy of most stem cell-based agents used in the treatment of malignant brain tumors, we found that stem cell distribution (i.e., only a fraction of stem cells applied capable of targeting tumors) are among the limiting factors. We provide guidelines for potential improvements in stem cell distribution. Specifically, we use an engineered tissue graft platform that replicates the in vivo microenvironment, and provide our data to validate that this culture platform is viable for producing stem cells that have better stem cell distribution than with the Petri dish culture system.
Core tip: Neural stem cells can target malignant brain tumors in preclinical models; however, clinical trials show dismal efficacy. We reviewed the literature and .found that only a small fraction of applied stem cells can move toward tumors while the majority of stem cells cannot reach the target tumor. To fill in the gap in stem cell technology, we propose a solution to train stem cells in a native tissue environment, allowing them to move through tissue barriers and arrive at the target tumor.
