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.

资助父母奖摘要 急性放射综合征（H-ARS）的造血亚综合征是由甚至 中度暴露于电离辐射，这对造血干细胞（HSC）是致命的， 骨髓（BM）。造血干细胞移植（HSCT）是一种潜在的挽救生命的治疗方法 对于H-ARS受害者;然而，由于通常相关的 移植物抗宿主病并发症最近的临床试验，包括我们的合作者， 已经证明，间充质基质/干细胞（MSC）输注预防/治疗移植物， 抗宿主病（GVHD）和减少HSCT后移植物衰竭。 MSC的这些有益效果是由于细胞的有效免疫调节特性。 此外，MSC具有许多其他治疗特性，显示出改善病理 与影响胃肠道系统、皮肤和肝脏的其他ARS综合征相关。因此，在本发明中， MSC具有治疗与电离辐射相关的各种病理的潜力 exposure. Ossium Health正在开发一种独特的BM衍生多能MSC来源， 已故器官捐献者这种细胞疗法，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的来源是供体匹配的 移植物（OssioStem-HSC）从相同供体获得。此外，大量的BM 可以从死亡的供体获得的MSC产生异常高的数量。这是 重要是，MSC支持HSCT的功效与传代呈负相关 因此，低传代OssioStem-M3上级从活体获得的“第三方”MSC。 供体，其必须通过许多传代扩增。 我们在这里建议优化分离OssioStem-M3的方法， 描述其物理特性和生物功能。我们亦建议 在H-ARS的大型（猪）和小型（小鼠）模型中证明了功效。最后，我们将建立 并测试下一代设备，以提高OssioStem的一致性和吞吐量- HSC生产。 这项研究计划的整体产品将是一个强大的生产过程和一个 令人信服的临床前包装，以证明确定性研究的合理性，以支持FDA批准H-ARS 根据动物规则。 补充摘要 要求提供补充资金，以弥补因不得不将 在原研究中心（Altasciences）停止研究后，在新研究中心进行猪H-ARS研究 程序.这些资金将用于支付猪H-ARS研究的预算缺口， 添加控制臂。请求的补充金额基于CRL提供的报价 2020年9月11日（报价编号CRL 272922）。4个研究组的报价金额 是389580美元加上可选的组织病理学费用（39 800美元）， 研究的总费用为四十二万九千三百八十元（即，389，580元+39，800元）。注意 组织病理学费用是原始报价的一部分，但考虑到 达到研究的原始预算金额。因此，要求补充 CRL研究的费用为115，380美元，即429，380美元和324，000美元之间的差额。