Effects of secretome obtained from normoxia-preconditioned human mesenchymal stem cells in traumatic brain injury rats

Chuang, Tai-Jen; Lin, Kao‐Chang; Chio, Chung-Ching; Wang, Che-Chuan; Chang, Chin-Ping; Kuo, Jinn‐Rung

doi:10.1097/ta.0b013e318265d128

Cited by 67 publications

(47 citation statements)

References 35 publications

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“…Preconditioning of neural stem cells with minocycline or interleukin 6 in vitro led to improved graft survival and increased secretion of trophic factors when transplanted into ischemic brains following transient focal ischemia, as well as improved histological and behavioral outcomes (Sakata et al , 2012a; Sakata et al , 2012b). In models of TBI, tail vein injection of MSCs or the MSC culture medium (secretome) alone was found to be protective (Chuang et al , 2012; Kim et al , 2010). Hypoxic preconditioning of MSCs significantly improved the release of trophic factors from cultured MCSs, and improved the behavior and histological outcomes following secretome injection (Chang et al , 2013).…”

Section: 0 Clinical Potential Of Preconditioningmentioning

confidence: 99%

Preconditioning provides neuroprotection in models of CNS disease: Paradigms and clinical significance

Stetler

Leak

Gan

et al. 2014

Progress in Neurobiology

171

140

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Preconditioning is a phenomenon in which brief episodes of a sublethal insult induce robust protection against subsequent lethal injuries. Preconditioning has been observed in multiple organisms and can occur in the brain as well as other tissues. Extensive animal studies suggest that the brain can be preconditioned to resist acute injuries, such as ischemic stroke, neonatal hypoxia/ischemia, trauma, and agents that are used in models of neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. Effective preconditioning stimuli are numerous and diverse, ranging from transient ischemia, hypoxia, hyperbaric oxygen, hypothermia and hyperthermia, to exposure to neurotoxins and pharmacological agents. The phenomenon of “cross-tolerance,” in which a sublethal stress protects against a different type of injury, suggests that different preconditioning stimuli may confer protection against a wide range of injuries. Research conducted over the past few decades indicates that brain preconditioning is complex, involving multiple effectors such as metabolic inhibition, activation of extra- and intracellular defense mechanisms, a shift in the neuronal excitatory/inhibitory balance, and reduction in inflammatory sequelae. An improved understanding of brain preconditioning should help us identify innovative therapeutic strategies that prevent or at least reduce neuronal damage in susceptible patients. In this review, we focus on the experimental evidence of preconditioning in the brain and systematically survey the models used to develop paradigms for neuroprotection, and then discuss the clinical potential of brain preconditioning. In a subsequent components of this two-part series, we will discuss the cellular and molecular events that are likely to underlie these phenomena.

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Section: 0 Clinical Potential Of Preconditioningmentioning

confidence: 99%

Preconditioning provides neuroprotection in models of CNS disease: Paradigms and clinical significance

Stetler

Leak

Gan

et al. 2014

Progress in Neurobiology

171

140

View full text Add to dashboard Cite

show abstract

“…The plethora of secreted trophic and immunomodulatory cytokines produced by MSCs (MSC secretome) have already been used to treat cardiovascular diseases [10] and proposed for the treatment of traumatic brain injuries [11], bone regeneration [12], or chronic wounds [13]. In addition to these two mechanisms, dental pulp stem cells (DPSCs) have been also shown to possess a functional role as pericytes, able to guide and support ECs to form new blood vessels through a VEGF-2-dependent mechanism [14].…”

Section: Introductionmentioning

confidence: 99%

Angiogenic Potential and Secretome of Human Apical Papilla Mesenchymal Stem Cells in Various Stress Microenvironments

Bakopoulou

Κritis

Andreadis

et al. 2015

Stem Cells and Development

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Stem cells from the apical papilla (SCAP) of human adult teeth are considered an accessible source of cells with angiogenic properties. The aims of this study were to investigate the endothelial transdifferentiation of SCAP, the secretion of pro-and antiangiogenic factors from SCAP, and the paracrine effects of SCAP when exposed to environmental stress to stimulate tissue damage. SCAP were exposed to serum deprivation (SD), glucose deprivation (GD), and oxygen deprivation/hypoxia (OD) conditions, individually or in combination. Endothelial transdifferentiation was evaluated by in vitro capillary-like formation assays, real-time polymerase chain reaction, western blot, and flow cytometric analyses of angiogenesis-related markers; secretome by antibody arrays and enzyme-linked immunosorbent assays (ELISA); and paracrine impact on human umbilical vein endothelial cells (HUVECs) by in vitro transwell migration and capillary-like formation assays. The short-term exposure of SCAP to glucose/oxygen deprivation (GOD) in the presence, but mainly in deprivation, of serum (SGOD) elicited a proangiogenesis effect indicated by expression of angiogenesis-related genes involved in vascular endothelial growth factor (VEGF)/VEGFR and angiopoietins/Tie pathways. This effect was unachievable under SD in normoxia, suggesting that the critical microenvironmental condition inducing rapid endothelial shift of SCAP is the combination of SGOD. Interestingly, SCAP showed high adaptability to these adverse conditions, retaining cell viability and acquiring a capillary-forming phenotype. SCAP secreted higher numbers and amounts of pro-(angiogenin, IGFBP-3, VEGF) and lower amounts of antiangiogenic factors (serpin-E1, TIMP-1, TSP-1) under SGOD compared with SOD or SD alone. Finally, secretome obtained under SGOD was most effective in inducing migration and capillary-like formation by HUVECs. These data provide new evidence on the microenvironmental factors favoring endothelial transdifferentiation of SCAP, uncovering the molecular mechanisms regulating their fate. They also validate the angiogenic properties of their secretome giving insights into preconditioning strategies enhancing their therapeutic potential.

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“…The observed effect was attributed to the presence of long noncoding RNA in the CM. Similarly, intravenous injection of MSC secretome to TBI rats significantly ameliorates motor deficits and cerebral infarction . They observed a significant reduction in neuronal cell loss and apoptosis, which lead to an improvement in functional recovery following treatment of TBI .…”

Section: Secretome As a Novel Therapy For Tbimentioning

confidence: 91%

Mesenchymal stromal cell secretome as a therapeutic strategy for traumatic brain injury

Muhammad

2019

BioFactors

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Traumatic brain injury (TBI) is a global health problem that is a common cause of disability and mortality. Despite the availability of many treatment options, none is capable of restoring functional and structural recovery of the damaged brain. Both the results of preclinical and clinical studies suggest the use of mesenchymal stromal cells (MSCs) as a therapeutic strategy for structural and functional recovery in TBI. However, recent evidence shows that the neuroprotective potential of MSCs is due to multiple secretions of bioactive molecules that modulate tissue microenvironment for tissue repair and regeneration. The results of preclinical studies indicate the therapeutic benefits of MSC secretome in TBI. Soluble bioactive molecules and extracellular vesicles are the various factors secreted by MSCs that can induce neurogenesis, angiogenesis, neovascularization, and anti‐inflammatory activities. This review highlights the neuroprotective effect of MSC secretome for the treatment of TBI. In addition, the possible challenges of secretome as biotherapeutics are identified and how some of the issues raised could be overcome for effective clinical application are also discussed.

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Effects of secretome obtained from normoxia-preconditioned human mesenchymal stem cells in traumatic brain injury rats

Cited by 67 publications

References 35 publications

Preconditioning provides neuroprotection in models of CNS disease: Paradigms and clinical significance

Preconditioning provides neuroprotection in models of CNS disease: Paradigms and clinical significance

Angiogenic Potential and Secretome of Human Apical Papilla Mesenchymal Stem Cells in Various Stress Microenvironments

Mesenchymal stromal cell secretome as a therapeutic strategy for traumatic brain injury

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