A meta-analysis of efficacy in pre-clinical human stem cell therapies for traumatic brain injury.
OBJECTIVE
Evaluate the preclinical evidence for human cell therapies for the treatment of traumatic brain injury (TBI), determine behavioral effect sizes for modified and non-modified cells, and identify variables that correlate with greater effect sizes.


METHODS
A literature search identified 58 animal studies of TBI using human stem cells. Each study received a Quality Index (QI) score based on existing guidelines. Effect sizes for cell therapies were determined for the most common behavioral endpoints: Morris Water Maze (MWM) latency/correct quadrant, and modified Neurological Severity Score (mNSS).


RESULTS
50 studies reported significant behavioral and/or histological improvement. The mean effect size for MWM latency was -1.08 for non-modified cells and -3.35 for modified cells. The mean effect size for MWM percent time in the correct quadrant was 1.66 for non-modified cells and 4.36 for modified cells. The mean effect size on the mNSS was -1.56 for non-modified cells and -4.46 for modified cells. No significant associations were found between methodological variables and effect sizes other than route of administration, where intra-lesional delivery resulted in larger effect sizes than i.v. or ventricular delivery. Studies with higher QI had smaller effect sizes; studies with larger effect sizes had greater standard errors. QI was not associated with journal impact factor.


CONCLUSIONS
Although human cell therapy studies report improved behavioral outcomes in the majority of preclinical literature, the methods are too heterogeneous to facilitate direct comparisons and bias was detected. Replication and standardization are needed to identify procedural variables to yield the best results. We encourage the use of quality criteria and rigor for future studies of human cell therapy in animal models of TBI.
Departments of Physical Medicine & Rehabilitation, UC Institute for Memory Impairments & Neurological Disorders, Room 2026 - Gross Hall, 845 Health Science Road, University of California, Irvine, CA 92697-1705, USA. Electronic address: ChangJan@uphs.upenn.edu.
Janessa
J
Chang
Department of Statistics, Center for Statistical Consulting, University of California, Irvine, Donald Bren Hall 2058, Irvine, CA 92697-1250, USA. Electronic address: phelanm@uci.edu.
Michael
M
Phelan
Departments of Physical Medicine & Rehabilitation, UC Institute for Memory Impairments & Neurological Disorders, Room 2026 - Gross Hall, 845 Health Science Road, University of California, Irvine, CA 92697-1705, USA; Neurological Surgery, Sue & Bill Gross Stem Cell Research Center, UC Institute for Memory Impairments & Neurological Disorders, Room 2026 - Gross Hall, 845 Health Science Road, University of California, Irvine, California 92697-1705, USA. Electronic address: Cummings@uci.edu.
Brian J
BJ
Cummings
D000818:Animals; D001930:Brain Injuries / Q000601:surgery*; D006801:Humans; D039781:PubMed / Q000706:statistics & numerical data; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000502:physiology*; D057170:Translational Research, Biomedical / Q000379:methods / Q000706:statistics & numerical data
Cell therapy; Cell transplantation; Meta-analysis; Neurotrauma; Review; Scientific rigor; Stem cell therapy; Traumatic brain injury