OssioStem-matched multipotent MSC (M3): banked, low passage bone marrow MSC for treatment of hematopoietic acute radiation syndrome.

OssioStem 匹配的多能 MSC (M3)：库存的低通道骨髓 MSC，用于治疗造血急性放射综合征。

• 批准号: 9913377
• 负责人: ERIK J. WOODS
• 金额: $ 49.5万
• 依托单位: OSSIUM HEALTH, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-19 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9913377
• 关键词: Acute Graft Versus Host Disease; Address; Affect; Allogenic; Aplastic Anemia; Aspirate substance; Autologous; Biological Process; Body Weight; Bone Marrow; Bone Marrow Cells; Bone Marrow Transplantation; Cadaver; Cell Count; Cell Therapy; Cells; Characteristics; Clinical Data; Clinical Research; Clinical Trials; Colony-Forming Units Assay; Complication; Cryopreservation; Data; Devices; Digestion; Dose; Engraftment; Exposure to; Failure; Family suidae; Goals; Harvest; Head; Health; Hematopoietic; Hematopoietic Cell Production; Hematopoietic Neoplasms; Hematopoietic Stem Cell Transplantation; Hematopoietic System; Hematopoietic stem cells; Immune Cell Suppression; Immune response; Immune system; Incidence; Industrial Accidents; Infusion procedures; Ionizing radiation; Licensure; Life; Liver; Living Donors; Medical; Medicine; Mesenchymal; Methods; Miniature Swine; Modeling; Mus; Nuclear; Nuclear Warfare; Occupational Accidents; Organ; Organ Donor; Pathology; Patients; Peptide Hydrolases; Phenotype; Procedures; Process; Production; Property; Protocols documentation; Radiation; Radiation Toxicity; Radiation exposure; Recovery; Research; Risk; Safety; Savings; Severities; Skin; Source; Spinal; Sternum; Stream; Stromal Cells; Supporting Cell; Syndrome; System; Terrorism; Testing; Therapeutic; Time; Tissue Donors; Tissues; Transplant Recipients; Transplantation; Validation; analog; animal rule; bone; cell injury; cell regeneration; cost effective; disorder prevention; effectiveness validation; efficacy study; gastrointestinal; gastrointestinal system; graft failure; graft vs host disease; immunoregulation; innovation; irradiation; long bone; mouse model; next generation; novel; peripheral blood; pre-clinical; prevent; product development; programs; reconstitution; rib bone structure; soft tissue; stem; stem cell therapy; stem cells; success; tissue regeneration; vertebra body

ABSTRACT The hematopoietic subsyndrome of acute radiation syndrome (H-ARS) is induced with even moderate exposure to ionizing radiation, which is lethal to hematopoietic stem cells (HSC) in the bone marrow (BM). Hematopoietic stem cell transplant (HSCT) is a potential life-saving treatment for H-ARS victims; however, it is not generally recommended due to commonly associated complication of graft-versus-host disease. Recent clinical trials, including that of our collaborator, have demonstrated that mesenchymal stromal/stem cell (MSC) infusions prevent/treat graft-versus-host-disease (GVHD) and reduce graft failure following HSCT. These salutary effects of MSC are due to potent immunomodulatory properties of the cells. Furthermore, MSC possess many other therapeutic properties shown to ameliorate pathologies associated with other ARS syndromes effecting the gastrointestinal system, skin and liver. Thus, MSC have the potential to treat the full spectrum of pathologies associated with ionizing radiation exposure. Ossium Health is developing a unique source of BM-derived multipotent MSC obtained from deceased organ donors. This cellular therapy, termed OssioStem-M3 (matched multipotent MSC) has a distinct advantage over other MSC sources in that it is donor-matched to a source for HSCT grafts (OssioStem-HSC) obtained from the same donors. Additionally, the large volumes of BM that can be obtained from a deceased donor yield exceptionally high numbers of MSC. This is important given that efficacy of MSC for supporting HSCT is negatively related to passage number; thus, low passage OssioStem-M3 is superior to “third party” MSC obtained from living donors which must be amplified through many passages. We propose here to optimize methods for isolation of OssioStem-M3 and thoroughly characterize their physical characteristics and biological function. We also propose to demonstrate efficacy in large (porcine) and small (mouse) models of H-ARS. Finally, we will build and test next generation devices for increasing the consistency and throughput of OssioStem-HSC production. The overall product of this research program will be a robust production process and a compelling preclinical package to justify definitive studies to support FDA approval for H-ARS under the Animal Rule.

抽象的 急性放射综合征（H-ARS）的造血亚综合征是由甚至 适度暴露于电离辐射，这对造血干细胞 (HSC) 是致命的 骨髓（BM）是一种潜在的挽救生命的方法。 然而，由于常见原因，一般不建议对 H-ARS 受害者进行治疗； 最近的临床试验，包括我们的移植物抗宿主病的相关并发症。 合作者已证明间充质基质/干细胞（MSC）输注 预防/治疗移植物抗宿主病 (GVHD) 并减少 HSCT 后的移植失败。 MSC 的这些有益作用归因于细胞强大的免疫调节特性。 此外，间充质干细胞还具有许多其他治疗特性，可改善病理状况 与影响胃肠系统、皮肤和肝脏的其他 ARS 综合征相关。 MSC 有潜力治疗与电离相关的全方位病理 辐射暴露。 Ossium Health 正在开发一种独特的 BM 来源的多能 MSC 来源，该来源来自 这种细胞疗法称为 OssioStem-M3（匹配的多能）。 MSC）与其他 MSC 来源相比具有明显的优势，因为它与来源进行供体匹配 适用于从同一供体获得的 HSCT 移植物 (OssioStem-HSC)。 从已故捐赠者身上获取的骨髓量会产生异常高的数量 MSC 的这一点很重要，因为 MSC 支持 HSCT 的功效与此呈负相关。 因此，低传代OssioStem-M3优于“第三方”获得的MSC 来自活体捐赠者，必须通过许多通道进行放大。 我们在此建议优化 OssioStem-M3 的分离方法并彻底 我们还建议表征它们的物理特征和生物功能。 最后，我们将在大型（猪）和小型（小鼠）模型中证明 H-ARS 的功效。 构建和测试下一代设备，以提高一致性和吞吐量 OssioStem-HSC 生产。 该研究计划的总体产品将是一个强大的生产过程和 令人信服的临床前方案证明最终研究的合理性，以支持 FDA 批准 H-ARS 根据动物规则。