Therapeutic Angiogenesis by Universal Donor Endometrial Regenerative Cells

通用供体子宫内膜再生细胞的治疗性血管生成

• 批准号: 7804372
• 负责人: ERIK J. WOODS
• 金额: $ 14.24万
• 依托单位: GENERAL BIOTECHNOLOGY, LLC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7804372
• 关键词: Adult; Age; Agreement; Allogenic; Amputation; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Autologous; Biological Models; Biotechnology; Blood Circulation; Bone Marrow; Bone Marrow Cells; Bone Marrow Stem Cell; Cell Count; Cell Therapy; Cell physiology; Cells; Clinical; Clinical Trials; Collaborations; Comorbidity; Data; Disease; Dose; Effectiveness; Endometrial; Evaluation; Functional disorder; Growth Factor; Harvest; Human; Image; Immune; Immunology; Immunosuppression; In Vitro; Inbred BALB C Mice; Inflammation; Inflammatory Response; Injection of therapeutic agent; Ischemia; Laboratories; Lasers; Ligation; Limb structure; Measures; Methods; Modeling; Mus; Muscle Cells; NOD/SCID mouse; Patients; Peripheral Blood Mononuclear Cell; Peripheral Blood Stem Cell; Peripheral arterial disease; Phase; Physiological; Population; Procedures; Process; Protocols documentation; Publishing; Route; Safety; Series; Side; Specialized Center; Stem cells; Symptoms; T-Lymphocyte; Therapeutic; Time; Work; abstracting; adult stem cell; angiogenesis; cytokine; efficacy evaluation; experience; femoral artery; implantation; in vivo; intraperitoneal; meetings; mouse model; novel; peripheral blood; point of care; prevent; public health relevance; regenerative; research study; response; stem cell population; therapeutic angiogenesis

DESCRIPTION (provided by applicant): Therapeutic Angiogenesis by Universal Donor Endometrial Regenerative Cells (ERC) Abstract The proposed study seeks to develop a practical, off the shelf, universal donor, cell therapy for an advanced form of peripheral artery disease termed "critical limb ischemia" (CLI). The major problem facing CLI patients is lack of proper circulation to the extremities. Although a basal level of collateral vessel formation has been documented in these patients, in many cases it is insufficient to prevent amputation. Methods of augmenting the process of collateral vessel formation through administration of angiogenic cytokines have largely failed clinically [1-3]. One explanation for this has been that cytokine administration was performed under conditions that were not physiological, both in terms of sequence and combinations. A more therapeutically promising method has been administration of autologous stem cells which secrete angiogenic cytokines under what appears to be more physiological conditions. Numerous clinical trials have demonstrated benefit using bone marrow and mobilized peripheral blood stem cell populations, which are reviewed in the following reference [4]. Unfortunately, adult autologous cells display reduced angiogenic capacity, especially in CLI patients [5, 6]. Additionally, the procedures for harvesting stem cells from the bone marrow or peripheral blood are considered to be dangerous in patients with CLI due to existing comorbidities [7, 8]. From a practical perspective autologous therapy can only be performed at specialized centers which have certified clean rooms and experience with cell processing. A novel stem cell population termed "endometrial regenerative cells" (ERC) has been identified by Medistem, Inc., that the company is developing with General BioTechnology, LLC as a "universal donor" population. To date this collaboration has resulted in a cell population that inhibits inflammatory responses, do not elicit T cell reactivity, and can survive in allogeneic and xenogeneic hosts in absence of immune suppression both in vitro and in vivo. Given the large amount of angiogenic growth factor secretion and ability to stimulate angiogenesis, the ERC may be a commercially viable substitute for autologous stem cell implantation that circumvents the problems of: extraction, age and disease associated stem cell dysfunction, and requirement for clean room facilities at the point of care. The current proposal seeks support to expand on existing efficacy evaluation so as to permit entry into Phase Ib/II clinical trials. PUBLIC HEALTH RELEVANCE: The project aims to augment existing safety and manufacturing data to submit a Phase Ib/II IND for treatment of critical limb ischemia using a novel adult stem cell population developed by Medistem termed Endometrial Regenerative Cells (ERC). Existing data demonstrates ERC are potently angiogenic, anti-inflammatory, and can be used in a "universal donor" manner, thus providing an easy to use, off the shelf cellular therapy for a condition that lacks therapeutic options besides amputation.

描述（由申请人提供）：通过通用供体子宫内膜再生细胞 (ERC) 进行治疗性血管生成 摘要拟议的研究旨在开发一种实用的、现成的通用供体细胞疗法，用于治疗称为“严重肢体缺血”(CLI) 的晚期外周动脉疾病。 CLI 患者面临的主要问题是四肢缺乏适当的循环。尽管这些患者的侧支血管形成已达到基础水平，但在许多情况下不足以防止截肢。通过施用血管生成细胞因子来增强侧支血管形成过程的方法在临床上基本上失败了[1-3]。对此的一种解释是，细胞因子的施用是在非生理条件下进行的，无论是顺序还是组合。一种更有治疗前景的方法是施用自体干细胞，这些干细胞在看起来更生理的条件下分泌血管生成细胞因子。大量临床试验已证明使用骨髓和动员外周血干细胞群的益处，以下参考文献对此进行了综述[4]。不幸的是，成体自体细胞的血管生成能力降低，特别是在 CLI 患者中 [5, 6]。此外，由于现有的合并症，从骨髓或外周血中采集干细胞的程序被认为对于 CLI 患者来说是危险的 [7, 8]。从实际角度来看，自体治疗只能在拥有经过认证的洁净室和细胞处理经验的专业中心进行。 Medistem, Inc. 已鉴定出一种称为“子宫内膜再生细胞”(ERC) 的新型干细胞群，该公司正在与 General BioTechnology, LLC 合作开发该干细胞群作​​为“通用供体”群。迄今为止，这项合作已经产生了一种细胞群，可以抑制炎症反应，不引发 T 细胞反应，并且可以在体外和体内没有免疫抑制的情况下在同种异体和异种宿主中存活。鉴于血管生成生长因子的大量分泌和刺激血管生成的能力，ERC可能是自体干细胞植入的商业上可行的替代品，它避免了以下问题：提取、年龄和疾病相关的干细胞功能障碍，以及护理点对洁净室设施的要求。目前的提案寻求支持以扩大现有的疗效评估，以便允许进入 Ib/II 期临床试验。 公共健康相关性：该项目旨在增强现有的安全性和制造数据，以提交 Ib/II 期 IND，用于使用 Medistem 开发的新型成体干细胞群（称为子宫内膜再生细胞 (ERC)）治疗严重肢体缺血。现有数据表明，ERC 具有强大的血管生成、抗炎作用，并且可以以“通用供体”方式使用，从而为除了截肢之外缺乏治疗选择的疾病提供一种易于使用的现成细胞疗法。