Efficacy of single and multiple injections of human umbilical tissue-derived cells following experimental stroke in rats.
BACKGROUND
Human umbilical tissue-derived cells (hUTC) are a promising source of cells for regenerative treatment of stroke. In this study, we tested the efficacy of hUTC in experimental stroke and whether multiple injections of hUTC provide additional therapeutic benefits as compared to a single injection.


METHODS
Adult male Wistar rats were subjected to 2 hours of middle cerebral artery occlusion (MCAo), and randomly selected animals were injected (i.v) with 3×10⁶ hUTC or with vehicle control (at day: 1, 1&3 or 1&7 after MCAo, n = 8-9/group). A battery of functional outcome tests was performed at days 1, 7, 14, 21, 28, 35, 42, 49, 56 and 63 after MCAo. Rats were sacrificed at 63 days after MCAo and lesion volumes were measured. To investigate the underlying mechanism of hUTC treatment of stroke, Von Willebrand Factor (vWF), and Synaptophysin immunostaining were performed.


RESULTS
All hUTC treated groups, single or multiple injections, had better functional recovery compared to control (p<0.01). There was no statistically significant difference between a single and multiple injections of hUTC (p = 0.23) or between different multiple injections groups (p>0.07) in functional outcome. All hUTC treatment groups showed significant increases in Synaptophysin, vascular density and perimeter compared to the control group (p<0.05). There was no statistically significant difference between a single and multiple injections of hUTC or between the two groups of multiple injections in all immunohistochemical measurements (p>0.1).


CONCLUSIONS
hUTC treatment significantly improves long term functional outcome after stroke and promotes vascular density and synaptic plasticity. At the proscribed doses, multiple injections of hUTC were not superior to single injection therapy in both functional outcome and histological assessments.
Department of Neurology, Henry Ford Hospital, Detroit, Michigan, United States of America.
Amjad
A
Shehadah
Jieli
J
Chen
Brian
B
Kramer
Alex
A
Zacharek
Yisheng
Y
Cui
Cynthia
C
Roberts
Mei
M
Lu
Michael
M
Chopp
D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D004195:Disease Models, Animal; D006801:Humans; D020244:Infarction, Middle Cerebral Artery; D007267:Injections; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000628:therapy*; D014470:Umbilical Cord / Q000166:cytology*