Neuroinflammation, Stem Cells, and Stroke.

Stroke remains a significant unmet clinical need with few treatment options that have a very narrow therapeutic window, thereby causing massive mortality and morbidity in the United States and around the world. Accordingly, finding safe and effective novel treatments with a wider therapeutic window stands as an urgent need in stroke. The progressive inflammation that occurs centrally and peripherally after stroke serves as a unique therapeutic target to retard and even halt the secondary cell death. Stem cell therapy represents a potent approach that can diminish inflammation in both the stroke brain and periphery (eg, spleen), advancing a paradigm shift from a traditionally brain-focused therapy to treating stroke as a neurological disorder with a significant peripheral pathology. The purpose of this review article is to highlight the inflammation-mediated secondary cell death that plagues both brain and spleen in stroke and to evaluate the therapeutic potential of stem cell therapy in dampening these inflammatory responses.

Enriched Environment and Exercise Enhance Stem Cell Therapy for Stroke, Parkinson's Disease, and Huntington's Disease.

Stem cells, specifically embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), induced pluripotent stem cells (IPSCs), and neural progenitor stem cells (NSCs), are a possible treatment for stroke, Parkinson's disease (PD), and Huntington's disease (HD). Current preclinical data suggest stem cell transplantation is a potential treatment for these chronic conditions that lack effective long-term treatment options. Finding treatments with a wider therapeutic window and harnessing a disease-modifying approach will likely improve clinical outcomes. The overarching concept of stem cell therapy entails the use of immature cells, while key in recapitulating brain development and presents the challenge of young grafted cells forming neural circuitry with the mature host brain cells. To this end, exploring strategies designed to nurture graft-host integration will likely enhance the reconstruction of the elusive neural circuitry. Enriched environment (EE) and exercise facilitate stem cell graft-host reconstruction of neural circuitry. It may involve at least a two-pronged mechanism whereby EE and exercise create a conducive microenvironment in the host brain, allowing the newly transplanted cells to survive, proliferate, and differentiate into neural cells; vice versa, EE and exercise may also train the transplanted immature cells to learn the neurochemical, physiological, and anatomical signals in the brain towards better functional graft-host connectivity.

Treating Metastatic Brain Cancers With Stem Cells.

Stem cell therapy may present an effective treatment for metastatic brain cancer and glioblastoma. Here we posit the critical role of a leaky blood-brain barrier (BBB) as a key element for the development of brain metastases, specifically melanoma. By reviewing the immunological and inflammatory responses associated with BBB damage secondary to tumoral activity, we identify the involvement of this pathological process in the growth and formation of metastatic brain cancers. Likewise, we evaluate the hypothesis of regenerating impaired endothelial cells of the BBB and alleviating the damaged neurovascular unit to attenuate brain metastasis, using the endothelial progenitor cell (EPC) phenotype of bone marrow-derived mesenchymal stem cells. Specifically, there is a need to evaluate the efficacy for stem cell therapy to repair disruptions in the BBB and reduce inflammation in the brain, thereby causing attenuation of metastatic brain cancers. To establish the viability of stem cell therapy for the prevention and treatment of metastatic brain tumors, it is crucial to demonstrate BBB repair through augmentation of vasculogenesis and angiogenesis. BBB disruption is strongly linked to metastatic melanoma, worsens neuroinflammation during metastasis, and negatively influences the prognosis of metastatic brain cancer. Using stem cell therapy to interrupt inflammation secondary to this leaky BBB represents a paradigm-shifting approach for brain cancer treatment. In this review article, we critically assess the advantages and disadvantages of using stem cell therapy for brain metastases and glioblastoma.