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Cellular therapies for neurological Injuries: bioreactors, potency, and coagulation

Published on February 29, 2024   31 min

Other Talks in the Series: Periodic Reports: Advances in Clinical Interventions and Research Platforms

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0:00
My name is Charles Cox. I'm at the Department of Pediatric Surgery at McGovern Medical School at UTHealth in Houston. Today, I'm going to speak about cellar therapies for neurological injuries, hitting on the topics of bioreactors, potency, and coagulation issues related to cell-based therapies.
0:21
There are three themes I'd like to discuss today. One is that cell therapeutics function as immunomodulatory agents that target the neuroinflammatory response to injury, functioning as endogenous bioreactors. Potency can be measured and linked to microglial activation in that the consideration of cellular therapeutic pro-coagulant effects are important for intravenous delivery and these can be managed with the appropriate anticoagulant agents. With these overarching observations, there appear to be clinically meaningfully improved outcomes using these approaches for neurologic injuries.
0:58
In terms of background, cell-based therapies have been proving useful for neurological injury and disease. When I'm speaking about cell-based therapies today, I'm speaking broadly, meaning, umbilical cord blood (UCB), bone marrow mononuclear cells (BMMNC), mesenchymal stromal cells (MSC), multipotent adult progenitor cells (MAPC). I'm speaking of these broadly and we'll distinguish between them throughout the course of the lecture, but common to all of these is there's probably a pleiotropic mechanism or mechanisms of action for which the putative benefits are derived. Mostly, this focuses on the modulation of the innate immune response to injury.
1:36
We diagramed this in which we showed that the principal bioreactor organ that drives this effect is the spleen. However, we've also shown the lung to be important in this regard. Intravenously injected cells travel to first the lung called the pulmonary first pass effect, where they interact with pulmonary interstitial macrophages, but the cells also then pass through the pulmonary circulation and are taken up by the spleen. It shouldn't be too surprising since the spleen effectively filters cells from the circulation. There, these cells interact with the immune cells of the spleen, serving to release anti-inflammatory cytokines, such as interleukin 4 (IL-4) and 10 (IL-10) as well as regulatory T cells. This release of anti-inflammatory cytokines and immune effector cells serves to interact with the blood brain barrier, preventing cerebral edema and mitigating the progression of injury. We studied this in traumatic brain injury models of controlled cortical impact injury or CCI.

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Cellular therapies for neurological Injuries: bioreactors, potency, and coagulation

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