scholarly journals Mesenchymal Stem Cells Expressing Brain-Derived Neurotrophic Factor Enhance Endogenous Neurogenesis in an Ischemic Stroke Model

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Chang Hyun Jeong ◽  
Seong Muk Kim ◽  
Jung Yeon Lim ◽  
Chung Heon Ryu ◽  
Jin Ae Jun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ischemic Stroke ◽  
Functional Recovery ◽  
Subventricular Zone ◽  
Neurotrophic Factor ◽  
Therapeutic Potential ◽  
Brain Derived Neurotrophic Factor ◽  
Neurological Deficits ◽  
Therapeutic Benefits

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.

scholarly journals Efficacy of mesenchymal stem cells in the treatment of ischemic stroke

2021 ◽  
Author(s):  
Gabriela Guy Duarte ◽  
Daniel Gonçalves de Oliveira ◽  
Felipe de Oliveira Breder ◽  
Guilherme Augusto Netto Nacif ◽  
Ivan Magalhães Viana
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ischemic Stroke ◽  
Cell Therapy ◽  
Therapeutic Potential ◽  
Neurological Deficits ◽  
Neurological Sequelae ◽  
Allogeneic Mscs ◽  
Ischemic Brain Tissue

Background: Ischemic stroke is one of the main causes of long-term disability in adults. In the search for therapies for neurological sequelae after stroke, several studies have been investigating the use of stem cells, especially mesenchymal stem cells (MSC). Objectives: To evaluate the efficacy of stem cell therapy in patients with neurological deficits due to stroke. Methods: A literature review was conducted based on clinical studies published on PubMed and Cochrane databases between 2013 and 2021. The search strategy (mesenchymal stem cells) AND (stroke) was used and 4 articles were selected. Results: In the selected studies, we observed the use of autologous or allogeneic MSCs, derived from bone marrow or umbilical cord. The cells were transplanted using intravenous, intra-arterial or intracerebral routes. The articles demonstrated safety in the use of MSC, with no reports of serious adverse effects causally related to cell therapy. The evaluation of efficacy was performed through the analysis of neurological condition scales such as the NIHSS, the modified Rankin Scale and the Fugl-Meyer Scale. The trials showed improvements in at least one of the scales after therapy, and the benefits focused, mainly, on the motor function of the patients. MSC are associated with the secretion of factors that promote inflammatory immunomodulation, angiogenesis and neurogenesis, contributing to brain repair. Conclusions: The use of MSCs in the treatment of ischemic stroke is safe and has therapeutic potential for repairing ischemic brain tissue. However, further studies are needed to prove the efficacy of MSCs in the rehabilitation of stroke.

Abstract 47: Age of Donor of Human Mesenchymal Stem Cells Drastically Affects Structural and Functional Recovery After Cell Therapy Following Ischemic Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Susumu Yamaguchi ◽  
Nobutaka Horie ◽  
Katsuya Satoh ◽  
Yoichi Morofuji ◽  
Tsuyoshi Izumo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Migration ◽  
Ischemic Stroke ◽  
Functional Recovery ◽  
Human Mesenchymal Stem Cells ◽  
Trophic Factor ◽  
Donor Age ◽  
Vessel Maturation ◽  
Factor Secretion

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.

scholarly journals Effects of intravenous administration of allogenic bone marrow- and adipose tissue-derived mesenchymal stem cells on functional recovery and brain repair markers in experimental ischemic stroke

2013 ◽  
Vol 4 (1) ◽  
pp. 11 ◽  
Author(s):  
María Gutiérrez-Fernández ◽  
Berta Rodríguez-Frutos ◽  
Jaime Ramos-Cejudo ◽  
M Teresa Vallejo-Cremades ◽  
Blanca Fuentes ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Ischemic Stroke ◽  
Functional Recovery ◽  
Intravenous Administration ◽  
Brain Repair ◽  
Allogenic Bone ◽  
Allogenic Bone Marrow

scholarly journals Cell-Based Therapy for Stroke

Stroke ◽  
2020 ◽  
Vol 51 (9) ◽  
pp. 2854-2862 ◽  
Author(s):  
You Jeong Park ◽  
Kuniyasu Niizuma ◽  
Maxim Mokin ◽  
Mari Dezawa ◽  
Cesar V. Borlongan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Ischemic Stroke ◽  
Cell Therapy ◽  
Therapeutic Potential ◽  
Host Tissue ◽  
In Vivo Models ◽  
Cell Based Therapy ◽  
Muse Cells

Stem cell-based regenerative therapies may rescue the central nervous system following ischemic stroke. Mesenchymal stem cells exhibit promising regenerative capacity in in vitro studies but display little to no incorporation in host tissue after transplantation in in vivo models of stroke. Despite these limitations, clinical trials using mesenchymal stem cells have produced some functional benefits ascribed to their ability to modulate the host’s inflammatory response coupled with their robust safety profile. Regeneration of ischemic brain tissue using stem cells, however, remains elusive in humans. Multilineage-differentiating stress-enduring (Muse) cells are a distinct subset of mesenchymal stem cells found sporadically in connective tissue of nearly every organ. Since their discovery in 2010, these endogenous reparative stem cells have been investigated for their therapeutic potential against a variety of diseases, including acute myocardial infarction, stroke, chronic kidney disease, and liver disease. Preclinical studies have exemplified Muse cells’ unique ability mobilize, differentiate, and engraft into damaged host tissue. Intravenously transplanted Muse cells in mouse lacunar stroke models afforded functional recovery and long-term engraftment into the host neural network. This mini-review article highlights these biological properties that make Muse cells an exceptional candidate donor source for cell therapy in ischemic stroke. Elucidating the mechanism behind the therapeutic potential of Muse cells will undoubtedly help optimize stem cell therapy for stroke and advance the field of regenerative medicine.

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