Human parthenogenetic neural stem cell grafts promote multiple regenerative processes in a traumatic brain injury model.

International Stem Cell Corporation human parthenogenetic neural stem cells (ISC-hpNSC) have potential therapeutic value for patients suffering from traumatic brain injury (TBI). Here, we demonstrate the behavioral and histological effects of transplanting ISC-hpNSC intracerebrally in an animal model of TBI. Methods: Sprague-Dawley rats underwent a moderate controlled cortical impact TBI surgery. Transplantation occurred at 72 h post-TBI with functional readouts of behavioral and histological deficits conducted during the subsequent 3-month period after TBI. We characterized locomotor, neurological, and cognitive performance at baseline (before TBI), then on days 0, 1, 7, 14, 30, 60, and 90 (locomotor and neurological), and on days 28-30, 58-60, and 88-90 (cognitive) after TBI. Following completion of behavioral testing at 3 months post-TBI, animals were euthanized by transcardial perfusion and brains harvested to histologically characterize the extent of brain damage. Neuronal survival was revealed by Nissl staining, and stem cell engraftment and host tissue repair mechanisms such as the anti-inflammatory response in peri-TBI lesion areas were examined by immunohistochemical analyses. Results: We observed that TBI groups given high and moderate doses of ISC-hpNSC had an improved swing bias on an elevated body swing test for motor function, increased scores on forelimb akinesia and paw grasp neurological tests, and committed significantly fewer errors on a radial arm water maze test for cognition. Furthermore, histological analyses indicated that high and moderate doses of stem cells increased the expression of phenotypic markers related to the neural lineage and myelination and decreased reactive gliosis and inflammation in the brain, increased neuronal survival in the peri-impact area of the cortex, and decreased inflammation in the spleen at 90 days post-TBI. Conclusion: These results provide evidence that high and moderate doses of ISC-hpNSC ameliorate TBI-associated histological alterations and motor, neurological, and cognitive deficits.

Granulocyte-colony stimulating factor and umbilical cord blood cell transplantation: Synergistic therapies for the treatment of traumatic brain injury.

Traumatic brain injury (TBI) is now characterized as a progressive, degenerative disease and continues to stand as a prevalent cause of death and disability. The pathophysiology of TBI is complex, with a variety of secondary cell death pathways occurring which may persist chronically following the initial cerebral insult. Current therapeutic options for TBI are minimal, with surgical intervention or rehabilitation therapy existing as the only viable treatments. Considering the success of stem-cell therapies in various other neurological diseases, their use has been proposed as a potential potent therapy for patients suffering TBI. Moreover, stem cells are highly amenable to adjunctive use with other therapies, providing an opportunity to overcome the inherent limitations of using a single therapeutic agent. Our research has verified this additive potential by demonstrating the efficacy of co-delivering human umbilical cord blood (hUCB) cells with granulocyte-colony stimulating factor (G-CSF) in a murine model of TBI, providing encouraging results which support the potential of this approach to treat patients suffering from TBI. These findings justify ongoing research toward uncovering the mechanisms which underlie the functional improvements exhibited by hUCB + G-CSF combination therapy, thereby facilitating its safe and effect transition into the clinic. This paper is a review article. Referred literature in this paper has been listed in the reference section. The datasets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors' experiences.

Biobridge concept in stem cell therapy for ischemic stroke.

Stroke causes a significant social and economic burden to the society. Despite advancement in awareness and prevention of stroke, there are still limited treatment options for stroke patients. One of the emerging experimental therapies for stroke is stem cell transplantation. The conventional belief of stem cell mechanisms is that the protective effects are produced by either cell replacement or releasing trophic factors. While the exact mechanisms of action of stem cells are not completely understood, recent evidence demonstrates another possible mechanism of stem cells. This new approach emphasizes on the formation of a biobridge between the damage area and the endogenous neurogenic niches of the brain. The transplanted cells can form a pathway which promotes the proliferation and migration of the endogenous stem cells. This paper discusses the use of stem cell transplantation for stroke with an emphasis on the new biobridge concept. Also discussed are the current challenges faced before this approach can advance to the clinical setting.

Stem cell therapy for sequestering neuroinflammation in traumatic brain injury: an update on exosome-targeting to the spleen.

Traumatic brain injury (TBI) manifests with acute and chronic cell death pathways leading to initial impacted injury and subsequent neurodegeneration. In particular, the secondary cell death, plagued by a massive and lingering neuroinflammatory response, contributes significantly to worsening outcomes of the progressive TBI pathology. Fortunately, neuroinflammation also provides an opportunity for therapeutic interventions. Limited treatment options currently exist for the disease, but stem cell-based therapies offer promise in promoting neuroprotection and neuroregeneration by mitigating central neuroinflammation as well as modulating peripheral inflammation via the spleen. Indeed, peripherally administered stem cells preferentially migrate to the spleen when injected after a neurovascular injury, advancing the concept that stem cells are inflammation-homing "biologics" and afford their neuroprotection primarily by abrogating the systemic inflammatory response. Accumulating preclinical evidence has revealed new insights on the systemic inflammation as a pathological culprit, but also arguably as a therapeutic target for stem cell therapies as a treatment for TBI and relevant neurovascular diseases. Here, we provide an update on recent scientific evidence supporting the stem cells' novel mechanism of sequestering the inflammation-mediated secondary cell death that closely accompanies the evolution of TBI pathology.

Utilizing pharmacotherapy and mesenchymal stem cell therapy to reduce inflammation following traumatic brain injury.

The pathologic process of chronic phase traumatic brain injury is associated with spreading inflammation, cell death, and neural dysfunction. It is thought that sequestration of inflammatory mediators can facilitate recovery and promote an environment that fosters cellular regeneration. Studies have targeted post-traumatic brain injury inflammation with the use of pharmacotherapy and cell therapy. These therapeutic options are aimed at reducing the edematous and neurodegenerative inflammation that have been associated with compromising the integrity of the blood-brain barrier. Although studies have yielded positive results from anti-inflammatory pharmacotherapy and cell therapy individually, emerging research has begun to target inflammation using combination therapy. The joint use of anti-inflammatory drugs alongside stem cell transplantation may provide better clinical outcomes for traumatic brain injury patients. Despite the promising results in this field of research, it is important to note that most of the studies mentioned in this review have completed their studies using animal models. Translation of this research into a clinical setting will require additional laboratory experiments and larger preclinical trials.