Next Generation Regenerative Therapy with Pim-1 Enhanced Cardiac Progenitor Cells

使用 Pim-1 增强型心脏祖细胞的下一代再生疗法

• 批准号: 9352458
• 负责人: MARK ALAN SUSSMAN
• 金额: $ 26.59万
• 依托单位: CARDIOCREATE, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-15 至 2019-05-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9352458
• 关键词: Achievement; Address; Adoptive Transfer; Affect; Aging; Ancillary Study; Animal Model; Autologous; Basic Science; Biological Assay; Biology; Bone Marrow Stem Cell; Businesses; Cardiac; Cardiac Output; Cardiovascular Diseases; Cause of Death; Cell Survival; Cells; Cicatrix; Clinical; Clinical Trials; Communities; Coupled; DNA Double Strand Break; Development; Down-Regulation; Enzymes; Ethnic Origin; Evolution; Family suidae; Future; Gene Expression; Genetic Engineering; Genetic Transcription; Goals; Harvest; Health; Heart; Heart Diseases; Heart failure; Human; In Vitro; Injection of therapeutic agent; Injury; International; Intervention; Investments; Laboratories; Laws; Legal patent; Length; Longevity; Mediating; Mesenchymal Stem Cells; Micronucleus Tests; Mitochondria; Modeling; Muscle; Myocardial; Myocardium; Occupations; Oncogenic; Outcome; Pathologic; Patients; Peer Review; Performance; Phase; Phase I Clinical Trials; Preclinical Testing; Property; Publications; Quality of life; Race; Recommendation; Regenerative Medicine; Regulation; Research; Research Support; Rest; Risk; Risk Assessment; Rodent; Safety; Shapes; Small Business Technology Transfer Research; Societies; Stem cells; Stress; Supporting Cell; Technology; Test Result; Testing; Therapeutic; Therapeutic Intervention; Therapeutic Studies; Tissues; Tumorigenicity; United States; Up-Regulation; Woman; base; bench to bedside; biological research; cell growth; genotoxicity; hemodynamics; improved; in vitro testing; industry involvement; innovation; meetings; men; new technology; next generation; novel; overexpression; regenerative; regenerative therapy; repaired; response; restoration; safety study; senescence; stem cell therapy; telomere; tissue regeneration; tumorigenesis; tumorigenic

PROJECT SUMMARY Myocardial regenerative therapy is poised to revolutionize the way heart failure is treated, but further improvements and enhanced products are needed to make this therapy truly safe and efficacious. Our company, CardioCreate, Inc., has pioneered the use of genetic engineering to enhance the regenerative potential of human Cardiac Progenitor Cells (CPCs) intended for autologous therapeutic utilization. CPCs support myocardial repair and improve cardiac performance through reduction of scar size and increased cardiac output. Pim-1, an endogenous constitutively activated enzyme found within CPCs, is produced in response to stress or pathologic injury in the myocardium. Pim-1 up-regulation enhances cell survival through mediating transcription, cell growth, proliferation, survival, and expansion of the CPC pool. Our legacy of over a decade of research on Pim-1 biology culminates with demonstration of remarkable regenerative effects mediated by adoptively transferred human Pim-1 enhanced CPCs in rodent and swine models with significantly improved cardiac performance relative to unmodified CPCs, bone marrow stem cells and mesenchymal stem cells. Our studies with human Pim-1 enhanced CPCs have also demonstrated the reversal of aging affects on human CPCs, such as down regulation of senescence markers, increased telomere length and mitochondrial activity and the enhancement of proliferation. The technology of using autologous Pim-1 enhanced Cardiac Progenitor Cells (CardioEnhancers™) represents a novel and efficacious treatment for heart failure, leading to improved health, longevity and wellbeing of our society. CardioEnhancers™ have the potential to provide a potential treatment and cure for cardiovascular disease, most specifically heart failure, which is the leading cause of death in the United States and equally affects men and women of all ethnicities and races. This proposal represents the convergent evolution of a decade of high-level mechanistic biological research coupled with entrepreneurial implementation of regenerative medicine solutions moving from the laboratory toward clinical setting implementation. In this Phase 1 STTR proposal the focus will be to complete initial in vitro safety profiling through a combination of oncogenicity and genotoxicity assessments necessary for FDA mandated IND approval. The Phase I goal is to generate the first battery of test results requested by the FDA to evaluate the safety profile of CardioEnhancers™. The innovation of this STTR rests in the trajectory toward implementation of next-generation stem cell therapy for treatment of heart failure. The significance of this STTR will allow CardioCreate, Inc. to move forward as a small business towards the objectives of finding an effective and safe therapeutic treatment for heart disease that may be used internationally, providing highly- skilled manufacturing jobs to US citizens and advancing the high-tech scientific achievement for our US research community.

项目概要 心肌再生疗法有望彻底改变心力衰竭的治疗方式，但进一步 需要改进和增强产品才能使这种疗法真正安全有效。我们的 CardioCreate, Inc. 公司率先利用基因工程来增强再生能力 人类心脏祖细胞（CPC）用于自体治疗的潜力。每次点击费用 通过减少疤痕大小和增加心脏功能来支持心肌修复并改善心脏功能 心输出量。 Pim-1 是 CPC 中发现的一种内源性组成型激活酶，产生于 对心肌应激或病理损伤的反应。 Pim-1 上调通过以下方式增强细胞存活 介导转录、细胞生长、增殖、存活和 CPC 库的扩展。我们的遗产超过 十年来 Pim-1 生物学研究达到顶峰，展示了显着的再生效果 在啮齿动物和猪模型中，由过继转移的人 Pim-1 增强的 CPC 介导，显着 相对于未修饰的 CPC、骨髓干细胞和间充质干细胞，心脏性能得到改善 细胞。我们对人类 Pim-1 增强 CPC 的研究也证明了衰老影响的逆转 人类 CPC，例如衰老标记物的下调、端粒长度和线粒体的增加 活性和增殖的增强。自体Pim-1增强心脏技术 祖细胞（CardioEnhancers™）代表了一种新颖且有效的心力衰竭治疗方法，可导致 改善我们社会的健康、寿命和福祉。 CardioEnhancers™ 有潜力提供 心血管疾病的潜在治疗和治愈方法，特别是心力衰竭，这是目前领先的治疗方法 是美国的死因，并且同样影响所有民族和种族的男性和女性。这 该提案代表了十年高水平机械生物学研究的趋同演变 加上从实验室开始的再生医学解决方案的创业实施 走向临床环境实施。在此第一阶段 STTR 提案中，重点将是完成初步工作 通过 FDA 所需的致癌性和遗传毒性评估相结合的体外安全性分析 强制 IND 批准。第一阶段的目标是生成 FDA 要求的第一批测试结果 评估 CardioEnhancers™ 的安全性。 STTR 的创新之处在于 实施下一代干细胞疗法治疗心力衰竭。此举的意义 STTR 将使 CardioCreate, Inc. 作为一家小型企业朝着寻找 可以在国际上使用的有效且安全的心脏病治疗方法，提供高度 为美国公民提供熟练的制造业工作并推动美国的高科技科学成就 研究社区。