Intravenous grafts of amniotic fluid-derived stem cells induce endogenous cell proliferation and attenuate behavioral deficits in ischemic stroke rats.
We recently reported isolation of viable rat amniotic fluid-derived stem (AFS) cells [1]. Here, we tested the therapeutic benefits of AFS cells in a rodent model of ischemic stroke. Adult male Sprague-Dawley rats received a 60-minute middle cerebral artery occlusion (MCAo). Thirty-five days later, animals exhibiting significant motor deficits received intravenous transplants of rat AFS cells or vehicle. At days 60-63 post-MCAo, significant recovery of motor and cognitive function was seen in stroke animals transplanted with AFS cells compared to vehicle-infused stroke animals. Infarct volume, as revealed by hematoxylin and eosin (H&E) staining, was significantly reduced, coupled with significant increments in the cell proliferation marker, Ki67, and the neuronal marker, MAP2, in the dentate gyrus (DG) [2] and the subventricular zone (SVZ) of AFS cell-transplanted stroke animals compared to vehicle-infused stroke animals. A significantly higher number of double-labeled Ki67/MAP2-positive cells and a similar trend towards increased Ki67/MAP2 double-labeling were observed in the DG and SVZ of AFS cell-transplanted stroke animals, respectively, compared to vehicle-infused stroke animals. This study reports the therapeutic potential of AFS cell transplantation in stroke animals, possibly via enhancement of endogenous repair mechanisms.
Department of Neurosurgery and Brain Repair, Center of Excellence for Aging and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, Florida, United States of America.
Naoki
N
Tajiri
Sandra
S
Acosta
Loren E
LE
Glover
Paula C
PC
Bickford
Alejandra
A
Jacotte Simancas
Takao
T
Yasuhara
Isao
I
Date
Marianna A
MA
Solomita
Ivana
I
Antonucci
Liborio
L
Stuppia
Yuji
Y
Kaneko
Cesar V
CV
Borlongan
D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D049109:Cell Proliferation; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000503:physiopathology; D007511:Ischemia / Q000150:complications; D019394:Ki-67 Antigen / Q000032:analysis; D020547:Lateral Ventricles / Q000378:metabolism / Q000473:pathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis; D019957:Motor Skills Disorders / Q000503:physiopathology / Q000517:prevention & control; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D012920:Social Behavior Disorders; D033581:Stem Cell Transplantation / Q000379:methods*; D020521:Stroke / Q000209:etiology / Q000503:physiopathology*; D013997:Time Factors
D019394:Ki-67 Antigen; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins