Gene transfer mediated by stem cell grafts to treat CNS injury.
BACKGROUND
Stem cell transplantation holds promise for promoting anatomical repair and functional recovery after traumatic or ischemic injuries to the CNS. Harnessing stem cells with therapeutic genes of interest is regarded as an attractive approach to augment therapeutic benefits of stem cell grafts.


METHODS
The advantage of stem-cell-mediated gene transfer is the engraftibility of stem cells that can ensure a long-term and stable expression of therapeutic genes. In addition, stem-cell-gene interaction may synergistically amplify therapeutic benefits. Delivery of classical neurotrophic factor genes provided neuroprotective and pro-regenerative effects in various injury models. Some studies employed therapeutic genes targeting post-injury microenvironment to support endogenous repair. Recent trials of stem-cell-mediated transfer of nonclassical growth factors showed relatively novel biological effects. Combinatorial strategies seem to have the potential to improve therapeutic efficacy.


CONCLUSIONS
Future development of induced pluripotent stem cells and novel scaffolding biomaterials will greatly expedite the advances in ex vivo gene therapy to treat CNS injury. Before moving to a clinical stage, rigorous preclinical evaluations are needed to identify an optimal gene or gene combination in different injury settings. Improving the safety of viral vectors will be a critical prerequisite for the clinical translation.
Ajou University School of Medicine, Brain Disease Research Center, Institute for Medical Sciences, Suwon, Republic of Korea.
Dong H
DH
Hwang
Soo R
SR
Jeong
Byung G
BG
Kim
D000818:Animals; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics*; D009416:Nerve Regeneration; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D033581:Stem Cell Transplantation; D016896:Treatment Outcome
D009414:Nerve Growth Factors