Stem Cell Therapy for Sequestration of Traumatic Brain Injury-Induced Inflammation

Traumatic brain injury (TBI) is one of the leading causes of long-term neurological disabilities in the world. TBI is a signature disease for soldiers and veterans, but also affects civilians, including adults and children. Following TBI, the brain resident and immune cells turn into a “reactive” state, characterized by the production of inflammatory mediators that contribute to the development of cognitive deficits. Other injuries to the brain, including radiation exposure, may trigger TBI-like pathology, characterized by inflammation. Currently there are no treatments to prevent or reverse the deleterious consequences of brain trauma. The recognition that TBI predisposes stem cell alterations suggests that stem cell-based therapies stand as a potential treatment for TBI. Here, we discuss the inflamed brain after TBI and radiation injury. We further review the status of stem cells in the inflamed brain and the applications of cell therapy in sequestering inflammation in TBI

Fighting the War Against COVID-19 via Cell-Based Regenerative Medicine: Lessons Learned from 1918 Spanish Flu and Other Previous Pandemics.

The human population is in the midst of battling a rapidly-spreading virus- Severe Acute Respiratory Syndrome Coronavirus 2, responsible for Coronavirus disease 2019 or COVID-19. Despite the resurgences in positive cases after reopening businesses in May, the country is seeing a shift in mindset surrounding the pandemic as people have been eagerly trickling out from federally-mandated quarantine into restaurants, bars, and gyms across America. History can teach us about the past, and today\u27s pandemic is no exception. Without a vaccine available, three lessons from the 1918 Spanish flu pandemic may arm us in our fight against COVID-19. First, those who survived the first wave developed immunity to the second wave, highlighting the potential of passive immunity-based treatments like convalescent plasma and cell-based therapy. Second, the long-term consequences of COVID-19 are unknown. Slow-progressive cases of the Spanish flu have been linked to bacterial pneumonia and neurological disorders later in life, emphasizing the need to reduce COVID-19 transmission. Third, the Spanish flu killed approximately 17 to 50 million people, and the lack of human response, overcrowding, and poor hygiene were key in promoting the spread and high mortality. Human behavior is the most important strategy for preventing the virus spread and we must adhere to proper precautions. This review will cover our current understanding of the pathology and treatment for COVID-19 and highlight similarities between past pandemics. By revisiting history, we hope to emphasize the importance of human behavior and innovative therapies as we wait for the development of a vaccine. Graphical Abstract

Viral Vectors Expressing Interleukin 2 for Cancer Immunotherapy

Interleukin 2 (IL-2) plays a crucial role in T cell growth and survival, enhancing the cytotoxic activity of natural killer and cytotoxic T cells and thus functioning as a versatile master proinflammatory anticancer cytokine. The FDA has approved IL-2 cytokine therapy for the treatment of metastatic melanoma and metastatic renal cell carcinoma. However, IL-2 therapy has significant constraints, including a short serum half-life, low tumor accumulation, and life-threatening toxicities associated with high doses. Oncolytic viruses (OVs) offer a promising option for cancer immunotherapy, selectively targeting and destroying cancer cells while sparing healthy cells. Numerous studies have demonstrated the successful delivery of IL-2 to the tumor microenvironment without compromising safety using OVs such as vaccinia, Sendai, parvo, Newcastle disease, tanapox, and adenoviruses. Additionally, by engineering OVs to coexpress IL-2 with other anticancer transgenes, the immune properties of IL-2 can be further enhanced. Preclinical and clinical studies have shown promising antitumor effects of IL-2-expressing viral vectors, either alone or in combination with other anticancer therapies. This review summarizes the therapeutic potential of IL-2-expressing viral vectors and their antitumor mechanisms of action.Peer reviewe

Adult Stem Cell Transplantation: Is Gender a Factor in Stemness?

Cell therapy now constitutes an important area of regenerative medicine. The aging of the population has mandated the discovery and development of new and innovative therapeutic modalities to combat devastating disorders such as stroke. Menstrual blood and Sertoli cells represent two sources of viable transplantable cells that are gender-specific, both of which appear to have potential as donor cells for transplantation in stroke. During the subacute phase of stroke, the use of autologous cells offers effective and practical clinical application and is suggestive of the many benefits of using the aforementioned gender-specific cells. For example, in addition to being exceptionally immunosuppressive, testis-derived Sertoli cells secrete many growth and trophic factors and have been shown to aid in the functional recovery of animals transplanted with fetal dopaminergic cells. Correspondingly, menstrual blood cells are easily obtainable and exhibit angiogenic characteristics, proliferative capability, and pluripotency. Of further interest is the ability of menstrual blood cells, following transplantation in stroke models, to migrate to the infarct site, secrete neurotrophic factors, regulate the inflammatory response, and be steered towards neural differentiation. From cell isolation to transplantation, we emphasize in this review paper the practicality and relevance of the experimental and clinical use of gender-specific stem cells, such as Sertoli cells and menstrual blood cells, in the treatment of stroke

Combined space stressors induce independent behavioral deficits predicted by early peripheral blood monocytes.

Interplanetary space travel poses many hazards to the human body. To protect astronaut health and performance on critical missions, there is first a need to understand the effects of deep space hazards, including ionizing radiation, confinement, and altered gravity. Previous studies of rodents exposed to a single such stressor document significant deficits, but our study is the first to investigate possible cumulative and synergistic impacts of simultaneous ionizing radiation, confinement, and altered gravity on behavior and cognition. Our cohort was divided between 6-month-old female and male mice in group, social isolation, or hindlimb unloading housing, exposed to 0 or 50 cGy of 5 ion simplified simulated galactic cosmic radiation (GCRsim). We report interactions and independent effects of GCRsim exposure and housing conditions on behavioral and cognitive performance. Exposure to GCRsim drove changes in immune cell populations in peripheral blood collected early after irradiation, while housing conditions drove changes in blood collected at a later point. Female mice were largely resilient to deficits observed in male mice. Finally, we used principal component analysis to represent total deficits as principal component scores, which were predicted by general linear models using GCR exposure, housing condition, and early blood biomarkers