scholarly journals Early Transplantation of Human Cranial Bone-derived Mesenchymal Stem Cells Enhances Functional Recovery in Ischemic Stroke Model Rats

2020 ◽  
Vol 60 (2) ◽  
pp. 83-93 ◽  
Author(s):  
Jumpei OSHITA ◽  
Takahito OKAZAKI ◽  
Takafumi MITSUHARA ◽  
Takeshi IMURA ◽  
Kei NAKAGAWA ◽  
...  
Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Susumu Yamaguchi ◽  
Nobutaka Horie ◽  
Katsuya Satoh ◽  
Yoichi Morofuji ◽  
Tsuyoshi Izumo ◽  
...  

Background and purpose: Cell transplantation therapy holds great potential to improve impairments after stroke. However, the importance of donor age on therapeutic efficacy is uncertain. We investigate regenerative capacity of transplanted cells focusing on donor age (young vs. old) for ischemic stroke. Methods: The value of platelet-derived growth factor (PDGF)-BB secreted from human mesenchymal stem cells (hMSC) was analyzed regarding in two age groups; young (20-30 years) and old (57-65 years) in vitro. Male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion, and received young or old hMSC trans-arterially at 24 h after stroke. Functional recovery was assessed with modified neurological severity score (mNSS). Structural recovery was assessed on neovascularization and endogenous cell migration as well as trophic factor secretion. Results: The value of PDGF-BB was significantly higher in young hMSC (40.47±4.29 pg/ml/10 4 cells) than that in old hMSC (25.35±3.16 pg/ml/10 4 cells; P =0.02) and negatively correlated with age ( P =0.048, r=-0.79, Spearman). Rats treated with young hMSC (3.7±0.6) showed better behavior recovery in mNSS with prevention of brain atrophy than that with control (6.1±0.5) or old (5.2±0.7) at D21 ( P <0.01). The number of RECA-1 and PDGFR-β double positive vessels in rat with young hMSC (113±48.6/mm 2 ) was higher than that in control (61.5±35.9/mm 2 ) or old (76.9±36.9/mm 2 ) suggesting vessel maturation ( P <0.01). Interestingly, migration of neural stem/progenitor cells expressing Musashi-1 positively correlated with astrocyte process alignment ( P <0.01, r=0.27; Spearman), which was more pronounced in young hMSC ( P <0.05). Conclusions: Aging of hMSC may be the critical factor which affects outcome of cell therapy, and transplantation of young hMSC could provide better functional recovery by vessel maturation and endogenous cell migration potentially due to dominance of trophic factor secretion.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Chang Hyun Jeong ◽  
Seong Muk Kim ◽  
Jung Yeon Lim ◽  
Chung Heon Ryu ◽  
Jin Ae Jun ◽  
...  

Numerous studies have reported that mesenchymal stem cells (MSCs) can ameliorate neurological deficits in ischemic stroke models. Among the various hypotheses that have been suggested to explain the therapeutic mechanism underlying these observations, neurogenesis is thought to be critical. To enhance the therapeutic benefits of human bone marrow-derived MSCs (hBM-MSCs), we efficiently modified hBM-MSCs by introduction of the brain-derived neurotrophic factor (BDNF) gene via adenoviral transduction mediated by cell-permeable peptides and investigated whetherBDNF-modified hBM-MSCs (MSCs-BDNF) contributed to functional recovery and endogenous neurogenesis in a rat model of middle cerebral artery occlusion (MCAO). Transplantation of MSCs induced the proliferation of 5-bromo-2′-deoxyuridine (BrdU-) positive cells in the subventricular zone. Transplantation of MSCs-BDNF enhanced the proliferation of endogenous neural stem cells more significantly, while suppressing cell death. Newborn cells differentiated into doublecortin (DCX-) positive neuroblasts and Neuronal Nuclei (NeuN-) positive mature neurons in the subventricular zone and ischemic boundary at higher rates in animals with MSCs-BDNF compared with treatment using solely phosphate buffered saline (PBS) or MSCs. Triphenyltetrazolium chloride staining and behavioral analysis revealed greater functional recovery in animals with MSCs-BDNF compared with the other groups. MSCs-BDNF exhibited effective therapeutic potential by protecting cell from apoptotic death and enhancing endogenous neurogenesis.


Neuroscience ◽  
2011 ◽  
Vol 175 ◽  
pp. 394-405 ◽  
Author(s):  
M. Gutiérrez-Fernández ◽  
B. Rodríguez-Frutos ◽  
J. Álvarez-Grech ◽  
M.T. Vallejo-Cremades ◽  
M. Expósito-Alcaide ◽  
...  

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