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: 10271661
• 负责人: ERIK J. WOODS
• 金额: $ 6.85万
• 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/10271661
• 关键词: Award; Biological Process; Bone Marrow; Budgets; Cell Therapy; Cells; Characteristics; Clinical Trials; Complication; Devices; Direct Costs; Exposure to; Family suidae; Funding; Grant; Health; Hematopoietic; Hematopoietic Cell Production; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Histopathology; Infusion procedures; Ionizing radiation; Life; Liver; Living Donors; Mesenchymal; Methods; Organ Donor; Parents; Pathology; Process; Production; Property; Radiation Toxicity; Radiation exposure; Research; Savings; Site; Skin; Source; Sum; Supporting Cell; Syndrome; Testing; Therapeutic; animal rule; arm; base; cost; gastrointestinal system; graft failure; graft vs host disease; immunoregulation; meetings; mouse model; next generation; pre-clinical; prevent; programs; stem cell therapy; stem cells

Abstract of funded parent award 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. Abstract for supplement Supplemental funds are requested to cover a budget deficit caused by having to place the porcine H-ARS study at a new study site after the original site (Altasciences) discontinued their program. These funds will be used to cover the porcine H-ARS study budgetary shortfall and add a control arm. The supplemental amount requested is based on a quote provided by CRL on September 11, 2020 (quote number CRL272922). The amount quoted for 4 study groups was $389,580. With the inclusion of the additional of optional histopathology costs ($39,800), the total cost for the study was brought to $429,380 (ie., the sum of $389,580 + $39,800). Note that the histopathology costs were part of the original quote but were removed in consideration of meeting the originally budgeted amount for the study. Thus, the request for supplementing the CRL study is $115,380 which is the difference between $429,380 and $324,000.

资助家长奖摘要 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治疗方法。 然而，对于 H-ARS 受害者，由于常见的相关原因，一般不建议这样做； 最近的临床试验，包括我们合作者的试验， 已证明间充质基质/干细胞（MSC）输注可预防/治疗移植物 抗宿主疾病（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 有潜力治疗与电离辐射相关的全谱病理学 接触。 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 HSCT 来源进行供体匹配 移植物（OssioStem-HSC）来自相同的捐赠者此外，还有大量的骨髓。 从已故捐献者身上获得的 MSC 产量极高。 鉴于 MSC 支持 HSCT 的功效与传代呈负相关，这一点很重要 因此，低传代 OssioStem-M3 优于从活体获得的“第三方”MSC 必须通过多次传代来扩增的供体。 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。 证明 H-ARS 的大型（猪）和小型（小鼠）模型的功效。 并测试下一代设备以提高 OssioStem 的一致性和吞吐量 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。 摘要 需要补充资金来弥补因必须安置而造成的预算赤字 在原研究中心 (Altasciences) 停止其研究后，在新的研究中心进行猪 H-ARS 研究 这些资金将用于弥补猪 H-ARS 研究的预算缺口和 添加控制臂所需的补充金额基于 CRL 提供的报价。 2020 年 9 月 11 日（报价号 CRL272922） 4 个研究组的报价金额。 包括额外的可选组织病理学费用（39,800 美元）， 该研究的总费用为 429,380 美元（即 389,580 美元 + 39,800 美元）。 组织病理学费用是原始报价的一部分，但考虑到后被删除 达到最初的研究预算金额，因此提出补充要求。 CRL 研究费用为 115,380 美元，即 429,380 美元和 324,000 美元之间的差额。