Neural stem cell biology may be well suited for improving brain tumor therapies.
Neural stem cells (NSCs) are capable of tremendous migratory potential to areas of pathology in the central nervous system. When implanted into a diseased or injured nervous system, NSCs can travel through great distances to and engraft within areas of discrete as well as diffuse abnormalities. Engraftment is often followed by integration into the local neural milieu, accompanied by stable gene expression from the NSCs. In addition, the pluripotency of NSCs endows them with the capability to replace diseased tissues in an appropriate manner. Recent evidence has also suggested that engrafted exogenous NSCs may have effects on the surrounding microenvironment, such as promoting protection and/or regeneration of host neural pathways. These characteristics of NSCs would seem to make them ideal agents for the treatment of various central nervous system pathologies, especially brain tumors. Brain tumors are generally difficult to treat because of the unique location of the lesions. In primary gliomas, the extensive infiltrative nature of the tumor cells presents a challenge for their effective and total eradication, hence the high rate of treatment failure and disease recurrence. In addition, normal brain structures are distorted and are often destroyed by the growing neoplasm. Even with effective therapy to surgically resect and destroy the neoplastic tissues, the brain is still injured, which often leaves the patient in a debilitated state. The unique ability of NSCs to "home in" on tumor cells followed by the delivery of a desired gene product makes the NSC a very promising agent in brain tumor therapy. Cytolytic viruses and genes coding for anti-tumor cytokines, pro-drug converting enzymes, and various neurotrophic factors have all been engineered into engraftable NSCs for delivery to tumors. When they are specially tagged, such injected NSCs can be visualized with the use of novel imaging techniques and tracked in vivo within living animals over real time. If the NSCs were also capable of participating in the subsequent repair and regeneration of the tumor-afflicted brain-at present a potential but as-yet-unproven aspect of this intervention-then its role in abetting anti-tumor therapy would be complete. It is important to emphasize, however, that the use of NSCs is adjunctive and is not a replacement for other therapies that should be used in parallel.
Yip
Stephen
S
The Burnham Institute, Program in Developmental & Regenerative Cell Biology, La Jolla, California 92037, USA.
Aboody
Karen S
KS
Burns
Michael
M
Imitola
Jaime
J
Boockvar
John A
JA
Allport
Jennifer
J
Park
Kook In
KI
Teng
Yang D
YD
Lachyankar
Mahesh
M
McIntosh
Tracy
T
O'Rourke
Donald M
DM
Khoury
Samia
S
Weissleder
Ralph
R
Black
Peter M
PM
Weiss
William
W
Snyder
Evan Y
EY
D001932:Brain Neoplasms / Q000235:genetics* / Q000628:therapy*; D002465:Cell Movement; D018925:Chemokines / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D005786:Gene Expression Regulation; D015316:Genetic Therapy; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D008959:Models, Neurological; D009416:Nerve Regeneration; D033581:Stem Cell Transplantation / Q000379:methods* / Q000639:trends
D018925:Chemokines; D018960:Hyaluronan Receptors; D004815:Epidermal Growth Factor