Soluble Factors and Mechanisms of Action of Mesenchymal Stem Cells in Traumatic Brain Injury and Organ Injury Induced by Trauma

2016 ◽  
pp. 248-269
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Brain Injury ◽  
Mechanisms Of Action ◽  
Organ Injury ◽  
Soluble Factors

scholarly journals Freshly Thawed Cryobanked Human Neural Stem Cells Engraft within Endogenous Neurogenic Niches and Restore Cognitive Function Following Chronic Traumatic Brain Injury

2020 ◽  
Author(s):  
Anna Badner ◽  
Emily K. Reinhardt ◽  
Theodore V. Nguyen ◽  
Nicole Midani ◽  
Andrew T. Marshall ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Brain Injury ◽  
Neural Stem Cells ◽  
Spatial Learning ◽  
Risk Taking ◽  
Mechanisms Of Action ◽  
Human Neural Stem Cells ◽  
Risk Taking Behavior

AbstractHuman neural stem cells (hNSCs) have potential as a cell therapy following traumatic brain injury (TBI). While various studies have demonstrated the efficacy of NSCs from on-going culture, there is a significant gap in our understanding of freshly thawed cells from cryobanked stocks – a more clinically-relevant source. To address these shortfalls, the therapeutic potential of our previously validated Shef-6.0 human embryonic stem cell (hESC)-derived hNSC line was tested following long-term cryostorage and thawing prior to transplant. Immunodeficient athymic nude rats received a moderate unilateral controlled cortical impact (CCI) injury. At 4-weeks post-injury, 6×105 freshly thawed hNSCs were transplanted into six injection sites (2 ipsi- and 4 contra-lateral) with 53.4% of cells surviving three months post-transplant. Interestingly, most hNSCs were engrafted in the meninges and the lining of lateral ventricles, associated with high CXCR4 expression and a chemotactic response to SDF1alpha (CXCL12). While some expressed markers of neuron, astrocyte, and oligodendrocyte lineages, the majority remained progenitors, identified through doublecortin expression (78.1%). Importantly, transplantation resulted in improved spatial learning and memory in Morris water maze navigation and reduced risk-taking behavior in an elevated plus maze. Investigating potential mechanisms of action, we identified an increase in ipsilateral host hippocampus cornu ammonis (CA) neuron survival, contralateral dentate gyrus (DG) volume and DG neural progenitor morphology as well as a reduction in neuroinflammation. Together, these findings validate the potential of hNSCs to restore function after TBI and demonstrate that long-term bio-banking of cells and thawing aliquots prior to use may be suitable for clinical deployment.Significance StatementThere is no cure for chronic traumatic brain injury (TBI). While human neural stem cells (hNSCs) offer a potential treatment, no one has demonstrated efficacy of thawed hNSCs from long-term cryobanked stocks. Frozen aliquots are critical for multisite clinical trials, as this omission impacted the use of MSCs for graft versus host disease. This is the first study to demonstrate the efficacy of thawed hNSCs, while also providing support for novel mechanisms of action – linking meningeal and ventricular engraftment to reduced neuroinflammation and improved hippocampal neurogenesis. Importantly, these changes also led to clinically relevant effects on spatial learning/memory and risk-taking behavior. Together, this new understanding of hNSCs lays a foundation for future work and improved opportunities for patient care.

Potential application of an injectable hydrogel scaffold loaded with mesenchymal stem cells for treating traumatic brain injury

2018 ◽  
Vol 6 (19) ◽  
pp. 2982-2992 ◽  
Author(s):  
Kun Zhang ◽  
Zhenqing Shi ◽  
Jiankang Zhou ◽  
Qu Xing ◽  
Shanshan Ma ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Hyaluronic Acid ◽  
Brain Injury ◽  
Sodium Alginate ◽  
Potential Application ◽  
Hydrogel Scaffold ◽  
Injectable Hydrogel ◽  
Tissue Scaffold

In this contribution, we developed an injectable hydrogel composed of sodium alginate and hyaluronic acid that acts as a tissue scaffold to create a more optimal microenvironment for the stem cells for potential application of traumatic brain injury implantation.

scholarly journals Engineered Mesenchymal Stem Cells with Enhanced Tropism and Paracrine Secretion of Cytokines and Growth Factors to Treat Traumatic Brain Injury

Stem Cells ◽  
2015 ◽  
Vol 33 (2) ◽  
pp. 456-467 ◽  
Author(s):  
Zhe Wang ◽  
Yu Wang ◽  
Zhiyong Wang ◽  
J. Silvio Gutkind ◽  
Zhongliang Wang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factors ◽  
Brain Injury ◽  
Paracrine Secretion

Paracrine factors of human mesenchymal stem cells increase wound closure and reduce reactive oxygen species production in a traumatic brain injury in vitro model

2013 ◽  
Vol 33 (7) ◽  
pp. 673-684 ◽  
Author(s):  
D Torrente ◽  
MF Avila ◽  
R Cabezas ◽  
L Morales ◽  
J Gonzalez ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Brain Injury ◽  
Wound Closure ◽  
Human Mesenchymal Stem Cells ◽  
Neuronal Population ◽  
Paracrine Factors ◽  
Neuroprotective Strategy

Traumatic brain injury (TBI) consists of a primary and a secondary insult characterized by a biochemical cascade that plays a crucial role in cell death in the brain. Despite the major improvements in the acute care of head injury victims, no effective strategies exist for preventing the secondary injury cascade. This lack of success might be due to that most treatments are aimed at targeting neuronal population, even if studies show that astrocytes play a key role after a brain damage. In this work, we propose a new model of in vitro traumatic brain-like injury and use paracrine factors released by human mesenchymal stem cells (hMSCs) as a neuroprotective strategy. Our results demonstrate that hMSC-conditioned medium increased wound closure and proliferation at 12 h and reduced superoxide production to control conditions. This was accompanied by changes in cell morphology and polarity index, as both parameters reflect the ability of cells to migrate toward the wound. These findings indicate that hMSC is an important regulator of oxidative stress production, enhances cells migration, and shall be considered as a useful neuroprotective approach for brain recovery following injury.

scholarly journals Interactome and reciprocal activation of pathways in topical mesenchymal stem cells and the recipient cerebral cortex following traumatic brain injury

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Ping K. Lam ◽  
Kevin K. W. Wang ◽  
Anthony W. I. Lo ◽  
Cindy S. W. Tong ◽  
Don W. C. Ching ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cerebral Cortex ◽  
Brain Injury

scholarly journals Topical application of adipose tissue-derived mesenchymal stem cells (ADMSCs) reduced cerebral edema in experimental traumatic brain injury (TBI)—a preliminary study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Hui Ma ◽  
Lian Xu Cui ◽  
Ping Kuen Lam ◽  
Cindy S. W. Tong ◽  
Kin K. Y. Lo ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Brain Injury ◽  
Topical Application ◽  
Cerebral Edema ◽  
Therapeutic Effects ◽  
Edema Formation ◽  
Hypoxic Precondition ◽  
Preliminary Study

Abstract Background Our previous studies showed that topical application of mesenchymal stem cells (MSCs) improved functional recovery in rat traumatic brain injury (TBI) model, and hypoxic precondition further enhanced the therapeutic effects of MSCs. There was no previous study on the attenuation of cerebral edema by MSCs. We investigated whether topical application of normoxic and hypoxic MSCs could reduce cerebral edema in an experimental TBI model. Methods Two million normoxic (N = 24) and hypoxic (N = 24) MSCs were applied topically to exposed the cerebral cortex in a controlled cortical impact (CCI) model. The MSCs were fixed in position with fibrin glue. No treatment was given to control animals (TBI only: n = 24). After surgery, four animals in each group were sacrificed daily (day 1 to day 6) for edema evaluation. Normal animals without TBI were used as reference (n = 4). The expressions of GFAP, AQP4, and MMP9 were also investigated by immunofluorescence staining and RT-PCR at day 3. Results The edema peaked within 3 days after TBI. Compared with the control, hypoxic MSCs reduced brain water content significantly (p < 0.05). Both hypoxic and normoxic MSCs downregulated the expression of MMP9 and normalized AQP4 distribution to astrocyte end feet. Conclusion Our preliminary study showed that topical application of hypoxic MSCs suppressed both vasogenic and cytotoxic edema formation.

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