Intranasal delivery of hypoxia-preconditioned bone marrow-derived mesenchymal stem cells enhanced regenerative effects after intracerebral hemorrhagic stroke in mice

Sun, Jiayi; Wei, Zheng; Gu, Xiaohuan; Zhang, James Ya; Zhang, Yongbo; Li, Jimei; Wei, Ling

doi:10.1016/j.expneurol.2015.03.011

Cited by 110 publications

(80 citation statements)

References 58 publications

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“…After transplantation in vivo , the pathological environment significantly decreases the self‐renewal and survival rate of MSCs. Evidence has shown that transplantation of hypoxia‐pretreated MSCs enhanced the therapeutic effects via up‐regulating the secretion of cytokines and growth factors . After hypoxia preconditioning (0.1–0.3% O 2 ), transplanted MSCs migrate into peri‐injury regions in the intracerebral haemorrhagic stroke brain and promote neurogenesis and neurological functional recovery through secreting various growth factors, including brain‐derived neurotrophic factor (BDNF), glial cell line‐derived neurotrophic factor (GDNF) and VEGF .…”

Section: Hypoxia Preconditioning For Improving the Cell Activities Ofmentioning

confidence: 99%

Preconditioning influences mesenchymal stem cell properties in vitro and in vivo

2018

J Cellular Molecular Medi

322

272

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Various diseases and toxic factors easily impair cellular and organic functions in mammals. Organ transplantation is used to rescue organ function, but is limited by scarce resources. Mesenchymal stem cell (MSC)‐based therapy carries promising potential in regenerative medicine because of the self‐renewal and multilineage potency of MSCs; however, MSCs may lose biological functions after isolation and cultivation for a long time in vitro. Moreover, after they are injected in vivo and migrate into the damaged tissues or organs, they encounter a harsh environment coupled with death signals due to the inadequate tensegrity structure between the cells and matrix. Preconditioning, genetic modification and optimization of MSC culture conditions are key strategies to improve MSC functions in vitro and in vivo, and all of these procedures will contribute to improving MSC transplantation efficacy in tissue engineering and regenerative medicine. Preconditioning with various physical, chemical and biological factors is possible to preserve the stemness of MSCs for further application in studies and clinical tests. In this review, we mainly focus on preconditioning and the corresponding mechanisms for improving MSC activities in vitro and in vivo; we provide a glimpse into the promotion of MSC‐based cell therapy development for regenerative medicine. As a promising consequence, MSC transplantation can be applied for the treatment of some terminal diseases and can prolong the survival time of patients in the near future.

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Section: Hypoxia Preconditioning For Improving the Cell Activities Ofmentioning

confidence: 99%

Preconditioning influences mesenchymal stem cell properties in vitro and in vivo

2018

J Cellular Molecular Medi

322

272

View full text Add to dashboard Cite

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“…Preconditioning has been successfully applied in cell therapy to protect the transplanted cells from apoptosis and increase their survival after transplantation in vivo . Hypoxic preconditioning (HP) was performed by exposing cells to non-lethal hypoxia (0.1–1%) for certain hours before transplantation, which is very effective in increasing transplanted cell survival and improving overall functional recovery after stroke or myocardial infarction (MI) (Hu et al , 2011b; Hu et al , 2008; Sun et al , 2015; Theus et al , 2008a; Wei et al , 2012). HP has also shown enhancement of cell differentiation in culture and after transplantation (Sart et al , 2014; Sun et al , 2015).…”

Section: Strategies To Enhance Cell Survival After Transplantation: Gmentioning

confidence: 99%

“…Furthermore, we demonstrated in a neonatal stroke model of rats that intranasally delivered BMSCs showed beneficial effects on brain development after stroke and that rat pups receiving HP-BMSCs developed better sensorimotor activity, olfactory functional recovery, and performed better in social behavioral tests (Wei et al , 2015). Recently, we showed that intranasal delivery of HP-BMSCs enhanced neurogenesis and angiogenesis after intracerebral hemorrhagic stroke in mice (Sun et al , 2015). …”

Section: Stem Cell/neural Progenitor Transplantation In Animal Modelsmentioning

confidence: 99%

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Stem cell transplantation therapy for multifaceted therapeutic benefits after stroke

Wei

Jiang

et al. 2017

Progress in Neurobiology

Self Cite

127

117

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One of the exciting advances in modern medicine and life science is cell-based neurovascular regeneration of damaged brain tissues and repair of neuronal structures. The progress in stem cell biology and creation of adult induced pluripotent stem (iPS) cells has significantly improved basic and pre-clinical research in disease mechanisms and generated enthusiasm for potential applications in the treatment of central nervous system (CNS) diseases including stroke. Endogenous neural stem cells and cultured stem cells are capable of self-renewal and give rise to virtually all types of cells essential for the makeup of neuronal structures. Meanwhile, stem cells and neural progenitor cells are well-known for their potential for trophic support after transplantation into the ischemic brain. Thus, stem cell-based therapies provide an attractive future for protecting and repairing damaged brain tissues after injury and in various disease states. Moreover, basic research on naïve and differentiated stem cells including iPS cells has markedly improved our understanding of cellular and molecular mechanisms of neurological disorders, and provides a platform for the discovery of novel drug targets. The latest advances indicate that combinatorial approaches using cell based therapy with additional treatments such as protective reagents, preconditioning strategies and rehabilitation therapy can significantly improve therapeutic benefits. In this review, we will discuss the characteristics of cell therapy in different ischemic models and the application of stem cells and progenitor cells as regenerative medicine for the treatment of stroke.

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“…Beside their capacity for self-renewal and differentiation into neuronal cells, transplanted BMSCs release paracrine factors for enhanced endogenous neuroprotection and neuro-repair, which may be the principal mechanisms of action [7]. Mesenchymal stem cells exhibit increased adherence to vascular endothelium in response to chemokines, adhesion molecules, and matrix metalloproteases and home to injury sites, rendering them ideal for treatment of retinal ischemic disorders [8]. …”

Section: Introductionmentioning

confidence: 99%

Bone-marrow mesenchymal stem-cell administration significantly improves outcome after retinal ischemia in rats

Mathew

Poston

Dreixler

et al. 2017

Graefes Arch Clin Exp Ophthalmol

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Purpose Ischemia-associated retinal degeneration is one of the leading causes of vision loss and to date, there are no effective treatment options. We hypothesized that delayed injection of bone marrow stem cells (BMSCs) 24 h after the onset of ischemia could effectively rescue ischemic retina from its consequences, including apoptosis, inflammation, and increased vascular permeability, thereby preventing retinal cell loss. Methods Retinal ischemia was induced in adult Wistar rats by increasing intraocular pressure (IOP) to 130–135 mm Hg for 55 min. BMSCs harvested from rat femur were injected into the vitreous 24 h post-ischemia. Functional recovery was assessed 7 days later using electroretinography (ERG) measurements of the a-wave, b-wave, P2, scotopic threshold response (STR), and oscillatory potentials (OP). The retinal injury and anti-ischemic effects of BMSCs were quantitated by measuring apoptosis, autophagy, inflammatory markers, and retinal-blood barrier permeability. The distribution and fate of BMSC were qualitatively examined using real-time fundus imaging, and retinal flat mounts. Results Intravitreal delivery of BMSCs significantly improved recovery of the ERG a- and b-waves, OP, negative STR, and P2, and attenuated apoptosis as evidenced by decreased TUNEL and caspase-3 protein levels. BMSCs significantly increased autophagy, decreased inflammatory mediators (TNF-α, IL-1β, IL-6), and diminished retinal vascular permeability. BMSCs persisted in the vitreous and were also found within ischemic retina. Conclusions Taken together, our results indicate that intravitreal injection of BMSCs rescued the retina from ischemic damage in a rat model. The mechanisms include suppression of apoptosis, attenuation of inflammation and vascular permeability, and preservation of autophagy.

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Intranasal delivery of hypoxia-preconditioned bone marrow-derived mesenchymal stem cells enhanced regenerative effects after intracerebral hemorrhagic stroke in mice

Cited by 110 publications

References 58 publications

Preconditioning influences mesenchymal stem cell properties in vitro and in vivo

Preconditioning influences mesenchymal stem cell properties in vitro and in vivo

Stem cell transplantation therapy for multifaceted therapeutic benefits after stroke

Bone-marrow mesenchymal stem-cell administration significantly improves outcome after retinal ischemia in rats

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