Controlled Cortical Impact Model of Mouse Brain Injury with Therapeutic Transplantation of Human Induced Pluripotent Stem Cell-Derived Neural Cells

Furmanski, Orion; Nieves, Michael D.; Doughty, Martin L.

doi:10.3791/59561

Cited by 7 publications

(5 citation statements)

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“…Cell Therapy TBI Mice Controlled cortical impact model of mouse brain injury with therapeutic transplantation of human induced pluripotent stem cell-derived neural cells [241] Cerebral Organoid TBI hiPSC Modeling traumatic brain injury in human cerebral organoids [198] Cell Therapy CD Mice Cell-based therapy for Canavan disease using human iPSC-derived NPCs and OPCs [122] Cerebral Organoid Stroke hiPSC…”

Section: Organoid Type Disease Cell Type Results Referencementioning

confidence: 99%

Induced Pluripotent Stem Cells and Organoids in Advancing Neuropathology Research and Therapies

Pazzin,

Previato,

Budelon Gonçalves

et al. 2024

Cells

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This review delves into the groundbreaking impact of induced pluripotent stem cells (iPSCs) and three-dimensional organoid models in propelling forward neuropathology research. With a focus on neurodegenerative diseases, neuromotor disorders, and related conditions, iPSCs provide a platform for personalized disease modeling, holding significant potential for regenerative therapy and drug discovery. The adaptability of iPSCs, along with associated methodologies, enables the generation of various types of neural cell differentiations and their integration into three-dimensional organoid models, effectively replicating complex tissue structures in vitro. Key advancements in organoid and iPSC generation protocols, alongside the careful selection of donor cell types, are emphasized as critical steps in harnessing these technologies to mitigate tumorigenic risks and other hurdles. Encouragingly, iPSCs show promising outcomes in regenerative therapies, as evidenced by their successful application in animal models.

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Section: Organoid Type Disease Cell Type Results Referencementioning

confidence: 99%

Induced Pluripotent Stem Cells and Organoids in Advancing Neuropathology Research and Therapies

Pazzin,

Previato,

Budelon Gonçalves

et al. 2024

Cells

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“…An adhesive removal test (ART) that records the time mice taken to notice and remove electrical tape from the forepaws within a familiar setting (Furmanski et al., 2019) reveals lateralized forepaw dysfunction (Figure 2). CCI injury produces an increase in both the latency to notice and remove adhesive tape from the contralateral right forepaw when compared to baseline, or when compared to sham controls for the first week PI (two‐way ANOVA with repeated measures: F (1, 52) = 38.12, n = 55, p < 0.0001; Figure 2a).…”

Section: Resultsmentioning

confidence: 99%

“…The ART was performed as previously described (Bouet et al., 2009; Furmanski et al., 2019). Briefly, electrical tape (3 × 5 mm strips) was manually applied with equal pressure to the ventral pads of each forepaw while the mouse was held immobilized.…”

Section: Methodsmentioning

confidence: 99%

Sensorimotor dysfunction in a mild mouse model of cortical contusion injury without significant neuronal loss is associated with increases in inflammatory proteins with innate but not adaptive immune functions

Nieves

Furmanski

Doughty

2020

J of Neuroscience Research

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Traumatic brain injury is a leading cause of mortality and morbidity in the United States. Acute trauma to the brain triggers chronic secondary injury mechanisms that contribute to long-term neurological impairment. We have developed a single, unilateral contusion injury model of sensorimotor dysfunction in adult mice. By targeting a topographically defined neurological circuit with a mild impact, we are able to track sustained behavioral deficits in sensorimotor function in the absence of tissue cavitation or neuronal loss in the contused cortex of these mice. Stereological histopathology and multiplex enzyme-linked immunosorbent assay proteomic screening confirm contusion resulted in chronic gliosis and the robust expression of innate immune cytokines and monocyte attractant chemokines IL-1β, IL-5, IL-6, TNFα, CXCL1, CXCL2, CXCL10, CCL2, and CCL3 in the contused cortex. In contrast, the expression of neuroinflammatory proteins with adaptive immune functions was not significantly modulated by injury. Our data support widespread activation of innate but not adaptive immune responses, confirming an association between sensorimotor dysfunction with innate immune activation in the absence of tissue or neuronal loss in our mice.

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“…Later studies involved predifferentiating stem cells into more lineage‐restricted precursors in order to reduce the likelihood of tumorigenesis . In an effort to reduce reliance on embryonic or fetal tissue, there have been a number of studies more recently focused on induced pluripotent stem cells derived from adult somatic cells …”

Section: Cell Therapy In Tbimentioning

confidence: 99%

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

et al. 2020

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Traumatic brain injury (TBI) causes death and disability in the United States and around the world. The traumatic insult causes the mechanical injury of the brain and primary cellular death. While a comprehensive pathological mechanism of TBI is still lacking, the focus of the TBI research is concentrated on understanding the pathophysiology and developing suitable therapeutic approaches. Given the complexities in pathophysiology involving interconnected immunologic, inflammatory, and neurological cascades occurring after TBI, the therapies directed to a single mechanism fail in the clinical trials. This has led to the development of the paradigm of a combination therapeutic approach against TBI. While there are no drugs available for the treatment of TBI, stem cell therapy has shown promising results in preclinical studies. But, the success of the therapy depends on the survival of the stem cells, which are limited by several factors including route of administration, health of the administered cells, and inflammatory microenvironment of the injured brain. Reducing the inflammation prior to cell administration may provide a better outcome of cell therapy following TBI. This review is focused on different therapeutic approaches of TBI and the present status of the clinical trials.

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Controlled Cortical Impact Model of Mouse Brain Injury with Therapeutic Transplantation of Human Induced Pluripotent Stem Cell-Derived Neural Cells

Cited by 7 publications

References 0 publications

Induced Pluripotent Stem Cells and Organoids in Advancing Neuropathology Research and Therapies

Induced Pluripotent Stem Cells and Organoids in Advancing Neuropathology Research and Therapies

Sensorimotor dysfunction in a mild mouse model of cortical contusion injury without significant neuronal loss is associated with increases in inflammatory proteins with innate but not adaptive immune functions

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

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