TY - JOUR
T1 - Fibroblast Growth Factor Type 1 (FGF1)-Overexpressed Adipose-Derived Mesenchaymal Stem Cells (AD-MSCFGF1) Induce Neuroprotection and Functional Recovery in a Rat Stroke Model
AU - Ghazavi, Hamed
AU - Hoseini, Seyed Javad
AU - Ebrahimzadeh-Bideskan, Alireza
AU - Mashkani, Baratali
AU - Mehri, Soghra
AU - Ghorbani, Ahmad
AU - Sadri, Kayvan
AU - Mahdipour, Elahe
AU - Ghasemi, Faezeh
AU - Forouzanfar, Fatemeh
AU - Hoseini, Azar
AU - Pasdar, Ali Reza
AU - Sadeghnia, Hamid Reza
AU - Ghayour-Mobarhan, Majid
N1 - Funding Information:
This work was supported by the Vice Chancellery for Research and Technology and the Stem Cell Research and Application Core of Mashhad University of Medical Sciences grants (921716) and by the Iran?s Vice-Presidency for Science and Technology grant (11/63941). The authors declare that they have no conflicts of interests.
Publisher Copyright:
© 2017, Springer Science+Business Media, LLC.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - Stroke, as the second most common cause of death, imposes a great financial burden on both the individual and society. Mesenchymal stem cells from rodents have demonstrated efficacy in experimental animal models of stroke due to enhanced neurological recovery. Since FGF1 (fibroblast growth factor 1) displays neuroprotective properties, for the first time, we investigated the effect of acute intravenous administration of FGF1 gene transfected adipose-derived mesenchymal stem cell (AD-MSCFGF1) on transient experimental ischemic stroke in rats. Stroke induction was made by transient middle cerebral artery occlusion (tMCAO). 2 × 106 AD-MSCFGF1 was administrated intravenously 30 min after carotid reperfusion. The ability of technetium99m-hexamethyl propylene amine oxime (99mTc-HMPAO)-labeled AD-MSCFGF1 to enter into ischemic brain was evaluated 2 h post injection. 24 h post operation, the neurological recovery (rotarod and Roger’s tests), the infarct volume (2, 3, 5-triphenyltetrazolium chloride, TTC assay), apoptosis rate (TUNEL assay), and the expression of FGF1 protein (western blotting) in the ischemic hemisphere were assessed. The 99mTc-HMPAO-labeled AD-MSCFGF1 could enter into the ischemic brain. Ischemic hemisphere activity was significantly higher than that observed in the contralateral hemisphere (p = 0.002). The administration of AD-MSCFGF1 resulted in significant improvement of neurological function tests and increased density of FGF1 protein in the peri-infarct area, while the infarct volume and the apoptotic index were significantly decreased, in comparison to the other treated groups. In conclusion, acute intravenous administration of AD-MSCFGF1 can be a novel and promising candidate approach for the treatment of ischemic stroke.
AB - Stroke, as the second most common cause of death, imposes a great financial burden on both the individual and society. Mesenchymal stem cells from rodents have demonstrated efficacy in experimental animal models of stroke due to enhanced neurological recovery. Since FGF1 (fibroblast growth factor 1) displays neuroprotective properties, for the first time, we investigated the effect of acute intravenous administration of FGF1 gene transfected adipose-derived mesenchymal stem cell (AD-MSCFGF1) on transient experimental ischemic stroke in rats. Stroke induction was made by transient middle cerebral artery occlusion (tMCAO). 2 × 106 AD-MSCFGF1 was administrated intravenously 30 min after carotid reperfusion. The ability of technetium99m-hexamethyl propylene amine oxime (99mTc-HMPAO)-labeled AD-MSCFGF1 to enter into ischemic brain was evaluated 2 h post injection. 24 h post operation, the neurological recovery (rotarod and Roger’s tests), the infarct volume (2, 3, 5-triphenyltetrazolium chloride, TTC assay), apoptosis rate (TUNEL assay), and the expression of FGF1 protein (western blotting) in the ischemic hemisphere were assessed. The 99mTc-HMPAO-labeled AD-MSCFGF1 could enter into the ischemic brain. Ischemic hemisphere activity was significantly higher than that observed in the contralateral hemisphere (p = 0.002). The administration of AD-MSCFGF1 resulted in significant improvement of neurological function tests and increased density of FGF1 protein in the peri-infarct area, while the infarct volume and the apoptotic index were significantly decreased, in comparison to the other treated groups. In conclusion, acute intravenous administration of AD-MSCFGF1 can be a novel and promising candidate approach for the treatment of ischemic stroke.
KW - Adipose-derived mesenchymal stem cells (AD-MSC)
KW - Fibroblast growth factor 1 (FGF1)
KW - Stroke
KW - Transfection
KW - Transient middle cerebral artery occlusion (tMCAO)
UR - http://www.scopus.com/inward/record.url?scp=85027105834&partnerID=8YFLogxK
U2 - 10.1007/s12015-017-9755-z
DO - 10.1007/s12015-017-9755-z
M3 - Article
C2 - 28795363
AN - SCOPUS:85027105834
VL - 13
SP - 670
EP - 685
JO - Stem Cell Reviews and Reports
JF - Stem Cell Reviews and Reports
SN - 1550-8943
IS - 5
ER -
