Potential of mesenchymal stem cells alone, or in combination, to treat traumatic brain injury

Willing, Alison E.; Das, Mahasweta; Howell, Mark; Mohapatra, Shyam S.; Mohapatra, Subhra

doi:10.1111/cns.13300

Cited by 20 publications

(22 citation statements)

References 173 publications

(191 reference statements)

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“…It is well known that the pathophysiologic mechanisms of TBI are poorly understood, and that the anatomy of the brain is uniquely complex with multiple cell types (neurons, astrocytes, oligodendrocytes, and microglia) and multiple subtypes of these cells [20]. At the beginning of the last century, Ramón y Cajal, who laid the foundations of modern neurobiology, postulated in his book Degeneration and Regeneration of the Nervous System (1913) " .…”

Section: Traumatic Brain Injurymentioning

confidence: 99%

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Cell-Based Therapies for Traumatic Brain Injury: Therapeutic Treatments and Clinical Trials

Bonilla

Zurita

2021

Biomedicines

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Traumatic brain injury (TBI) represents physical damage to the brain tissue that induces transitory or permanent neurological disabilities. TBI contributes to 50% of all trauma deaths, with many enduring long-term consequences and significant medical and rehabilitation costs. There is currently no therapy to reverse the effects associated with TBI. An increasing amount of research has been undertaken regarding the use of different stem cells (SCs) to treat the consequences of brain damage. Neural stem cells (NSCs) (adult and embryonic) and mesenchymal stromal cells (MSCs) have shown efficacy in pre-clinical models of TBI and in their introduction to clinical research. The purpose of this review is to provide an overview of TBI and the state of clinical trials aimed at evaluating the use of stem cell-based therapies in TBI. The primary aim of these studies is to investigate the safety and efficacy of the use of SCs to treat this disease. Although an increasing number of studies are being carried out, few results are currently available. In addition, we present our research regarding the use of cell therapy in TBI. There is still a significant lack of understanding regarding the cell therapy mechanisms for the treatment of TBI. Thus, future studies are needed to evaluate the feasibility of the transplantation of SCs in TBI.

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Section: Traumatic Brain Injurymentioning

confidence: 99%

“…It is for the science of the future to change, if possible, this harsh decree" [21]. This note is widely quoted in the literature to remind us that we are still a long way from understanding the true nature of the brain [20].…”

Section: Traumatic Brain Injurymentioning

confidence: 99%

Cell-Based Therapies for Traumatic Brain Injury: Therapeutic Treatments and Clinical Trials

Bonilla

Zurita

2021

Biomedicines

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“…Autologous BM-MSC therapy was also proven to be safe and effective when administrated through lumbar puncture in the subacute stage of TBI [33]. There are also ongoing clinical trials evaluating the therapeutic effects of stem cells in TBI patients in which the results are highly anticipated and briefly summarized in the related papers [34,35].…”

Section: Traumamentioning

confidence: 99%

Therapeutic Applications of Stem Cells and Extracellular Vesicles in Emergency Care: Futuristic Perspectives

Öztürk

Elçin

Koca

et al. 2020

Stem Cell Rev and Rep

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Regenerative medicine (RM) is an interdisciplinary field that aims to repair, replace or regenerate damaged or missing tissue or organs to function as close as possible to its physiological architecture and functions. Stem cells, which are undifferentiated cells retaining self-renewal potential, excessive proliferation and differentiation capacity into offspring or daughter cells that form different lineage cells of an organism, are considered as an important part of the RM approaches. They have been widely investigated in preclinical and clinical studies for therapeutic purposes. Extracellular vesicles (EVs) are the vital mediators that regulate the therapeutic effects of stem cells. Besides, they carry various types of cargo between cells which make them a significant contributor of intercellular communication. Given their role in physiological and pathological conditions in living cells, EVs are considered as a new therapeutic alternative solution for a variety of diseases in which there is a high unmet clinical need. This review aims to summarize and identify therapeutic potential of stem cells and EVs in diseases requiring acute emergency care such as trauma, heart diseases, stroke, acute respiratory distress syndrome and burn injury. Diseases that affect militaries or societies including acute radiation syndrome, sepsis and viral pandemics such as novel coronavirus disease 2019 are also discussed. Additionally, featuring and problematic issues that hamper clinical translation of stem cells and EVs are debated in a comparative manner with a futuristic perspective.

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“…PGE 2 binding with the EP2 receptor activates adenylate cyclase and phosphorylates various cellular targets can lead to multiple neuroprotective processes, including anti‐inflammation. In a similar fashion, Greig and co‐investigators 9 reveal that the small molecular weight drug (‐)‐phenserine tartrate (PhenT), originally developed for Alzheimer's disease, effectively abrogates mild and moderate TBI via mitigation of multiple components of programmed neuronal cell death, including oxidative stress, glutamate excitotoxicity, neuroinflammation, and effectively reversed injury‐induced gene pathways leading to chronic neurodegeneration. Both PGE 2 and PhenT treatments produced motor and cognitive improvements in TBI animals, 8,9 further increasing their clinical application potential.…”

mentioning

confidence: 96%

“…The articles in this special issue probe the pathology of CNS trauma, including TBI and SIC, and begin to understand potential therapeutic modalities. Along this line, the proposed cell therapy 5‐7 and drug and immunization treatments 8‐10 offer new directions in the management of TBI. These promising therapies warrant serious consideration as we translate them into clinical applications.…”

mentioning

confidence: 99%

Traumatic brain injury

Bailes

Borlongan

2020

CNS Neurosci Ther

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Traumatic brain injury (TBI) stands as a major cause of mortality and morbidity around the world. More than 30% of injury-related deaths in the United States involve TBI. 1,2 TBI entails two phases of injury, namely an initial head trauma via an external force that results in mechanical damage to brain tissue and a secondary biochemical cascades including inflammation, apoptosis, oxidative stress, and other pathophysiological complications that propel further brain degeneration. 3,4 Treatment options for TBI remain limited, indicating an urgent need to examine novel therapeutic modalities designed to protect or to regenerate the injured brain.This special issue compiles recent advances in TBI research focused on cell-based regenerative medicine and pharmacologic therapies. We envision that rigorous translational research will provide the necessary testbed for ushering safe and effective therapeutics from the laboratory to the clinic.Yasuhara and colleagues 5 review the field of cell therapy for TBI and a relevant brain disorder, stroke. Here, they identify technical challenges that accompany cell transplantation, such as cell dose, timing, and delivery. In particular, they outline important preclinical investigations that are warranted to translate induced pluripotent stem cells for clinical applications in TBI and stroke.Next, our laboratory further elucidates the potential benefits, as well as caveats associated with cell therapy for TBI. 6 This review paper tackles neuroinflammation as a major cell death mechanism that closely approximates the secondary cell death in TBI. We also recognize that because neuroinflammation ensues immediately after TBI onset but also persists over time, it presents a large therapeutic window for cell therapy intervention. We provide encouraging laboratory studies detailing the success of cell transplantation in mitigating the inflammation-plagued secondary cell death of TBI.Recognizing that cell therapy may not be a magic bullet, Willing and co-workers 7 offer a combination therapy. Here, they show the potential of combining cell therapy with drugs that target signaling pathways of the neuro-immune-inflammatory axis. The concept posits that since singular targeting of a cell death pathway mostly fails, drugs that engage multiple pathways will likely promote improved sequestration of degenerative processes for TBI.The next two papers indeed advance novel drugs that encompass multiple targeting of cell death pathways. The paper by Dore and teammates demonstrate the potential of engaging the lipid metabolite prostaglandin E2 (PGE 2 ) as therapeutic targets to treat repetitive concussions and other acute brain injuries. 8 PGE 2 binding with the EP2 receptor activates adenylate cyclase and phosphorylates various cellular targets can lead to multiple neuroprotective processes, including anti-inflammation. In a similar fashion, Greig and co-investigators 9 reveal that the small molecular weight drug (-)-phenserine tartrate (PhenT), originally developed for Alzheimer's disease, effectivel...

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Potential of mesenchymal stem cells alone, or in combination, to treat traumatic brain injury

Cited by 20 publications

References 173 publications

Cell-Based Therapies for Traumatic Brain Injury: Therapeutic Treatments and Clinical Trials

Cell-Based Therapies for Traumatic Brain Injury: Therapeutic Treatments and Clinical Trials

Therapeutic Applications of Stem Cells and Extracellular Vesicles in Emergency Care: Futuristic Perspectives

Traumatic brain injury

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