Stromal cell therapy as a treatment against Gastrointestinal Acute Radiation Syndrome (GI-ARS)

基质细胞疗法作为胃肠道急性放射综合症（GI-ARS）的治疗方法

• 批准号: 9886178
• 负责人: Chandan Guha
• 金额: $ 55.73万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-03-09 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9886178
• 关键词: Abdomen; Acute; Adipose tissue; Agonist; Alginates; Allogenic; Awareness; Biological Markers; Blood Vessels; Bone Marrow; Bone Marrow Transplantation; Brain Injuries; CSF3 gene; Cell Therapy; Cell Transplantation; Cell physiology; Cells; Chemicals; Cicatrix; Cutaneous; Data; Development; Differentiation and Growth; Dose; Encapsulated; Endothelial Cells; Epithelial; Epithelium; Exposure to; Failure; Gastrointestinal Injury; Gastrointestinal tract structure; General Population; Genetic; Growth Factor; Hydrogels; ITGAM gene; Immune; Immune response; Incidence; Inflammatory; Injury; Intestinal Neoplasms; Intestines; Ionizing radiation; LGR5 gene; Laboratories; Libraries; Life; Lung; Lymphoid Cell; Mediating; Mesenchymal; Mesenchymal Stem Cells; Mononuclear; Mus; Myelogenous; Myeloid Cells; Myofibroblast; Natural regeneration; Nuclear Accidents; Organ; Pharmacology; Physiological; Placenta; Population; Production; Proteomics; Publishing; Radiation; Radiation Accidents; Radiation Dose Unit; Radiation Injuries; Radiation Tolerance; Radiation Toxicity; Radiation exposure; Risk; Signal Transduction; Site; Source; Stress; Stromal Cells; Supporting Cell; Syndrome; Techniques; Technology; Terrorism; Testing; Therapeutic; Time; Tissues; Toll-like receptors; Transplantation; Whole-Body Irradiation; cardiovascular injury; cell regeneration; cytokine therapy; epithelium regeneration; exosome; experimental study; extracellular vesicles; first responder; gastrointestinal; gastrointestinal function; improved; induced pluripotent stem cell; injured; intestinal epithelium; irradiation; macrophage; mass casualty; mortality; post-transplant; radiation mitigator; recruit; regenerative; repaired; restoration; stem cell niche; stem cells; therapy development; tissue regeneration; transcriptome; vector

ABSTRACT Exposure to high doses of ionizing radiation results in injury to multiple organs causing acute radiation syndrome. Bone marrow transplant (BMT) is an effective strategy to replace and regenerate injured stem cells, it has proven to be very successful in mitigating radiation induced acute injury to the bone marrow (BM- ARS). However at higher radiation doses and for non-hematopoietic injuries, BM mitigation alone is not sufficient to rescue from mortality. For instance, acute radiation injury to the gastro-intestinal tract (GI-ARS) is not mitigated by BMT or cytokine therapies. We have shown that GI-ARS can be successfully mitigated by bone marrow adherent stromal cell transplant (BMASCT), consisting mainly of stromal and myeloid cells. BMASCT in its current form is limiting when a large population is at risk, HLA libraries and well as allogeneic cell transplant therapies are essential to developing this therapy for a large population. Current application proposes various strategies to develop a radiomitigating cell product that can be used in a mass casualty scenario.

摘要 暴露于高剂量电离辐射导致多器官损伤，引起急性辐射 综合征骨髓移植（BMT）是一种有效的替代和再生受损干细胞的策略 细胞，它已被证明是非常成功的减轻辐射诱导的急性损伤骨髓（BM- ARS）。然而，在较高的辐射剂量下和对于非造血损伤，单独的BM缓解不是 足以拯救死亡。例如，胃肠道急性辐射损伤（GI-ARS）是 BMT或细胞因子疗法不能缓解。我们已经证明，GI-ARS可以成功地减轻， 骨髓贴壁基质细胞移植（BMASCT），主要由基质细胞和髓样细胞组成。 目前形式的BMASCT在大规模人群处于风险中时是有限的，HLA文库和同种异体造血干细胞移植是有限的。 细胞移植疗法对于开发用于大群体的这种疗法是必要的。当前应用程序 提出了各种策略，以开发一种可用于大规模伤亡的放射性细胞产品 场景