Human mesenchymal stem cell transplantation protects against cerebral ischemic injury and upregulates interleukin-10 expression in Macaca fascicularis

Li, Jiamei; Zhu, Hua; Liu, Ying; Qin, Li; Lu, Shan; Feng, Ming; Xu, Yanfeng; Huang, Lan; Ma, Chi; An, Yu; Zhao, Robert Chunhua; Wang, Renzhi; Qin, Chuan

doi:10.1016/j.brainres.2010.03.080

Cited by 80 publications

(49 citation statements)

References 32 publications

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“…We hypothesized that stem cell transplantation could modulate the inflammatory response in the hyper-acute stage of cerebral ischemia. The use of human mesenchymal stem cells to treat focal cerebral ischemia in animal models has been extensively studied [8][9][10] .…”

Section: Introductionmentioning

confidence: 99%

Human umbilical cord blood mesenchymal stem cell transplantation suppresses inflammatory responses and neuronal apoptosis during early stage of focal cerebral ischemia in rabbits

et al. 2014

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Aim: Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) have been shown to ameliorate cerebral ischemia in animal models. In this study we investigated the effects of hUCB-MSCs on inflammatory responses and neuronal apoptosis during the early stage of focal cerebral ischemia in rabbits. Methods: Focal cerebral ischemia was induced in male New Zealand rabbits by occlusion of MCA for 2 h. The blood samples were collected at different time points prior and during MCAO-reperfusion. The animals were euthanized 3 d after MCAO, and the protein levels of IL-1β, IL-6, IL-10, and TNF-α in the serum and peri-ischemic brain tissues were detected using Western blot and ELISA, respectively. Inflammatory cell infiltration, neuronal apoptosis and neuronal density were measured morphologically. hUCB-MSCs (5×10 6 ) were iv injected a few minutes after MCAO. Results: The serum levels of IL-1β, IL-6, and TNF-α were rapidly increased, and peaked at 2 h after the start of MCAO. hUCB-MSC transplantation markedly and progressively suppressed the ischemia-induced increases of serum IL-1β, IL-6, and TNF-α levels within 6 h MCAO-reperfusion. Focal cerebral ischemia decreased the serum level of IL-10, which was prevented by hUCB-MSC transplantation. The expression of IL-1β, IL-6, IL-10, and TNF-α in the peri-ischemic brain tissues showed similar changes as in the serum. hUCB-MSC transplantation markedly suppressed the infiltration of inflammatory cells, and increased the neuronal density around the ischemic region. Furthermore, hUCB-MSC transplantation significantly decreased the percentage of apoptosis around the ischemic region. Conclusion: hUCB-MSCs transplantation suppresses inflammatory responses and neuronal apoptosis during the early stage focal cerebral ischemia in rabbits.

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Section: Introductionmentioning

confidence: 99%

Human umbilical cord blood mesenchymal stem cell transplantation suppresses inflammatory responses and neuronal apoptosis during early stage of focal cerebral ischemia in rabbits

et al. 2014

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“…The animal study using bone marrow stem cells in treating myocardial infarction confirmed that stem cells not only differentiate into cardiac cells and vascular cells, but also activate cardiac stem cells by, via the paracrine route, secreting active substances and growth factors (21). A study using bone marrow stem cells in cerebral ischaemia treatment found that, stem cells can improve the neurological function of ischaemic tissue and strengthen the expression of IL-10, which has neuroprotective effects (22).…”

Section: Discussionmentioning

confidence: 96%

Treatment for chronic ischaemia-induced bladder detrusor dysfunction using bone marrow mesenchymal stem cells: An experimental study

Song

Zhang²,

Zhang³

et al. 2011

Int J Mol Med

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Abstract. The mechanism of ischaemia-induced bladder dysfunction is not entirely clear, but is thought to be a result of the ischaemia-related M-receptor hypersensitivity to acetylcholine. In addition to nerve injury, ischaemia may cause bladder detrusor fibrosis and urethra de-epithelialization. Bladder dysfunctions caused by bladder outlet obstruction (BOO) and aging detrusor were considered to be associated with chronic ischaemia. To date, there has been no effective treatment for the histological and functional changes of the bladder caused by bladder ischaemia. The present study evaluated the feasibility and effectiveness of using bone marrow mesenchymal stem cells in the treatment of chronic ischaemia-induced bladder detrusor dysfunction in an experimental model. Bone marrow mesenchymal stem cells from Sprague-Dawley (SD) rats were injected into the common iliac artery of experimental animals, then bilateral iliac arteries were ligated and doxazosin mesylate was intragastrically administered. Eight weeks later, urodynamic examination and intravesical pressure measurements were performed on experimental animals. Histological changes of the taken bladder from sacrificed SD rats were evaluated by immunohistochemistry and trichrome staining and the images captured were analyzed by a software program. The average intravesical pressure and detrusor contraction power of the ischaemia group was 16.21±5.26 and 17.26±5.72; those of the experimental group were 24.02±10.06 and 25.84±11.99; the average intravesical pressure and detrusor contraction power of the control group was 28.56±4.48 and 29.57±5.01. The average intravesical pressure and detrusor contraction power of the ischaemia group were significantly lower than those of the experimental and control group, while no significant difference was shown between the experimental and control groups. 5-Bromo-2'-deoxyuridine (BrdU) staining for the experimental group was positive. The percentage of the smooth muscle content in the bladder wall was (25.21±6.28)%, (49.38±6.32)% and (48.00±17.39)% for ischaemia, experimental and control group, respectively. The percentage of smooth muscle in the bladder wall of the ischaemia group was significantly lower than that of the experimental and control group, while no significant difference was observed between the experimental and control groups. The number of nerve fibers per high power field of the experimental group was significantly higher than that of the ischaemia group, but lower than the control group. In conclusion, the percentage of smooth muscle content and the number of nerve cells per high power field decreases in ischaemia bladder, with detrusor contractility decreased. Injection of stem cell suspension into the common iliac artery in rats with ischaemic bladder, followed by intragastric administration of doxazosin mesylate, makes transplanted stem cells regenerate in the bladder tissue, increases the percentage of smooth muscle content and nerve cells per high power field in the bladder wall, and improve bladder d...

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“…This study also found an increase in BDNF and NGF in the ipsilateral hemisphere of MSC-treated rats at 7 days post-stroke; however, they did not distinguish whether these trophic factors were produced by the donor or host cells. Li et al (2010) show that transplanting human MSCs into the injury penumbra 1 week following experimental cerebral ischemia in monkeys decreased apoptotic cell death and the lesion volume. Human MSCs transplanted into the injury cavity 1 week following experimental TBI in rats lead to enhanced cell survival in the hippocampus and improved functional recovery, and this was further improved when the MSCs were delivered within a collagen I scaffold (Xiong et al, 2009).…”

Section: Neuroprotectionmentioning

confidence: 90%

“…Indeed, Aizman et al (2009) demonstrate that human MSC-derived ECM promotes differentiation of cortical cells into neurons, astrocytes and oligodendrocytes and also enhances neuronal neurite networks compared to single ECM proteins. Transplantation of MSCs augments endogenous regeneration following experimental ischemic stroke (Bao et al, 2011;Li et al, 2010;Li et al, 2002;Xin et al, 2010;Yoo et al, 2008) and TBI (Mahmood et al, 2004;Xiong et al, 2009). For example, both Bao et al (2011) and Yoo et al (2008) show that intracerebral transplantation of human MSCs 3 days following experimental cerebral ischemia in rats increases proliferation and migration of host neural stem cells and also decreases their apoptosis, thus enhancing neurogenesis.…”

Section: Neuroregenerationmentioning

confidence: 99%

Mesenchymal Stromal Cells to Treat Brain Injury

Tate¹,

Case²

2012

Advanced Topics in Neurological Disorders

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Human mesenchymal stem cell transplantation protects against cerebral ischemic injury and upregulates interleukin-10 expression in Macaca fascicularis

Cited by 80 publications

References 32 publications

Human umbilical cord blood mesenchymal stem cell transplantation suppresses inflammatory responses and neuronal apoptosis during early stage of focal cerebral ischemia in rabbits

Human umbilical cord blood mesenchymal stem cell transplantation suppresses inflammatory responses and neuronal apoptosis during early stage of focal cerebral ischemia in rabbits

Treatment for chronic ischaemia-induced bladder detrusor dysfunction using bone marrow mesenchymal stem cells: An experimental study

Mesenchymal Stromal Cells to Treat Brain Injury

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