Dataset Information

Isolation and Characterization of Neural Progenitor Cells From Bone Marrow in Cell Replacement Therapy of Brain Injury.

ABSTRACT: Many studies supported that bone marrow mesenchymal stem cells (BM-MSCs) can differentiate into neural cells, but few researchers detected mature and function of nerve cells, especially in vivo study. Some researchers even suggested that BM-MSCs transplantation would not be able to differentiate into functional neural cells. To figure out the dispute, this study examined bone marrow-derived sphere-like cells, harvested via neural stem cell suspension culture, then identified as bone marrow-derived neural progenitor cells (BM-NPCs) by finding the expression of neural progenitor cells genes and proteins, neural progenitor cells characteristic and nerve cell differentiation induced through both methods. Moreover, BM-NPCs transplantation showed long-term survival and improved the ethological and histological indexes of brain injury rats, demonstrating functional nervous cells differentiated from BM-NPCs. These in vitro and in vivo results confirmed BM-NPCs differentiating into mature and functional nerve cells. This study provided valuable experimental data for BM-NPCs, suggesting a potential alternative treatment of central nervous injury disease.

SUBMITTER: Bai WF

PROVIDER: S-EPMC7080866 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Isolation and Characterization of Neural Progenitor Cells From Bone Marrow in Cell Replacement Therapy of Brain Injury.

Bai Wen-Fang WF Zhang Yuling Y Xu Weicheng W Li Weikun W Li Meihui M Yuan Fengying F Luo Xun X Zhang Mingsheng M

Frontiers in cellular neuroscience 20200312

Many studies supported that bone marrow mesenchymal stem cells (BM-MSCs) can differentiate into neural cells, but few researchers detected mature and function of nerve cells, especially <i>in vivo</i> study. Some researchers even suggested that BM-MSCs transplantation would not be able to differentiate into functional neural cells. To figure out the dispute, this study examined bone marrow-derived sphere-like cells, harvested <i>via</i> neural stem cell suspension culture, then identified as bon ...[more]

PMID: 32226361

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Project description:Preclinical studies using bone marrow derived cells to treat traumatic brain injury have demonstrated efficacy in terms of blood-brain barrier preservation, neurogenesis, and functional outcomes. Phase 1 clinical trials using bone marrow mononuclear cells infused intravenously in children with severe traumatic brain injury demonstrated safety and potentially a central nervous system structural preservation treatment effect. This study sought to confirm the safety, logistic feasibility, and potential treatment effect size of structural preservation/inflammatory biomarker mitigation in adults to guide Phase 2 clinical trial design. Adults with severe traumatic brain injury (Glasgow Coma Scale 5-8) and without signs of irreversible brain injury were evaluated for entry into the trial. A dose escalation format was performed in 25 patients: 5 controls, followed 5 patients in each dosing cohort (6, 9, 12 ×106 cells/kg body weight), then 5 more controls. Bone marrow harvest, cell processing to isolate the mononuclear fraction, and re-infusion occurred within 48 hours after injury. Patients were monitored for harvest-related hemodynamic changes, infusional toxicity, and adverse events. Outcome measures included magnetic resonance imaging-based measurements of supratentorial and corpus callosal volumes as well as diffusion tensor imaging-based measurements of fractional anisotropy and mean diffusivity of the corpus callosum and the corticospinal tract at the level of the brainstem at 1 month and 6 months postinjury. Functional and neurocognitive outcomes were measured and correlated with imaging data. Inflammatory cytokine arrays were measured in the plasma pretreatment, posttreatment, and at 1 and 6 month follow-up. There were no serious adverse events. There was a mild pulmonary toxicity of the highest dose that was not clinically significant. Despite the treatment group having greater injury severity, there was structural preservation of critical regions of interest that correlated with functional outcomes. Key inflammatory cytokines were downregulated. Treatment of severe, adult traumatic brain injury using an intravenously delivered autologous bone marrow mononuclear cell infusion is safe and logistically feasible. There appears to be a treatment signal as evidenced by central nervous system structural preservation, consistent with previous pediatric trial data. Inflammatory biomarkers are downregulated after cell infusion. Stem Cells 2016 Video Highlight: https://youtu.be/UiCCPIe-IaQ Stem Cells 2017;35:1065-1079.

Dataset Information

Isolation and Characterization of Neural Progenitor Cells From Bone Marrow in Cell Replacement Therapy of Brain Injury.

Publications

Isolation and Characterization of Neural Progenitor Cells From Bone Marrow in Cell Replacement Therapy of Brain Injury.

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