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

基本信息

批准号：
10359772
负责人：
Chandan Guha
金额：
$ 54.23万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-03-09 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10359772
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 Data Development Differentiation and Growth Dose Encapsulated Endothelial Cells Epithelial Exposure to Gastrointestinal Injury Gastrointestinal tract structure General Population Genetic Growth Factor Hydrogels ITGAM gene Immune Immune response Incidence Inflammatory Injury Intestines Ionizing radiation LGR5 gene Laboratories Libraries Life Lymphoid Cell Mediating Mesenchymal Mesenchymal Stem Cells Mononuclear Multiple Organ Failure 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 Regenerative capacity Risk Signal Transduction Site Skin injury Source Stress Stromal Cells Supporting Cell Syndrome Techniques Technology Terrorism Testing Therapeutic Time Tissues Toll-like receptors Transplantation Whole-Body Irradiation cardiovascular injury cytokine therapy efficacious treatment epithelium regeneration exosome experimental study extracellular vesicles first responder gastrointestinal gastrointestinal function improved induced pluripotent stem cell injured intestinal epithelium irradiation lung injury macrophage mass casualty morphogens mortality post-transplant radiation mitigator recruit regenerative repaired restoration stem cell niche stem cell self renewal stem cells therapy development tissue regeneration transcriptome transplantation therapy vector

项目摘要

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.

抽象的暴露于高剂量的电离辐射会导致多个器官受伤，导致急性辐射综合征。骨髓移植（BMT）是替换和再生受伤茎的有效策略细胞，事实证明，它在减轻辐射引起骨髓急性损伤方面非常成功（BM- ars）。但是，在较高的辐射剂量和非造成造成损伤的情况下，仅BM缓解不是足以从死亡率中救出。例如，胃肠道急性辐射损伤（GI-ARS）为不受BMT或细胞因子疗法缓解。我们已经表明，Gi-ARS可以通过骨髓粘附基质细胞移植（BMASCT），主要由基质和髓样细胞组成。当大量人口处于风险，HLA库和同种异体状态时，BMASCT的当前形式将有限细胞移植疗法对于为大量人群开发这种疗法至关重要。当前申请提出了开发可用于大规模伤亡的放射性细胞产品的各种策略设想。