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.

项目摘要 心肌再生疗法被中毒，以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，以使该疗法真正安全有效。我们的 公司Cardiocreate，Inc。已开创了使用基因工程来增强再生的使用 用于自体治疗利用的人类心脏祖细胞（CPC）的潜力。 CPCS 通过减少疤痕大小并增加，支持心肌修复并改善心脏性能 心输出。 PIM-1是一种内生配置，用于激活CPC中发现的酶，在 对心肌压力或病理损伤的反应。 PIM-1上调通过 介导CPC库的转录，细胞生长，增殖，存活和膨胀。我们的遗产 关于PIM-1生物学的十年研究最终表明了显着再生作用 通过适当转移的人PIM-1在啮齿动物和猪模型中提高CPC介导 相对于未修饰的CPC，骨髓干细胞和间充质茎的改善心脏性能改善 细胞。我们对人类PIM-1增强CPC的研究也证明了衰老的逆转影响 人CPC，例如对感应标记的下调，增加了端粒长度和线粒体 活性和增殖的增强。使用自体PIM-1增强心脏的技术 祖细胞（Cardioenhancers™）代表了一种新颖有效的心力衰竭治疗，导致 改善了我们社会的健康，寿命和福祉。 Cardioenhancers™有可能提供 潜在的治疗和心血管疾病的治疗，最特别是心力衰竭，这是领先的 在美国的死亡原因，同样影响所有种族和种族的男人和女人。这 提案代表了十年的高级机械生物学研究的收敛演化 再加上从实验室移动的再生医学解决方案的企业家实施 朝着临床环境实施。在此阶段1 sttr提案中，重点将是完成初始 通过结合FDA所需的致癌性和遗传毒性评估的结合，体外安全分析 要求IND批准。 I阶段目标是生成FDA要求的第一个电池测试结果 评估Cardioenhancers™的安全性概况。这种sttr的创新基于朝向的轨迹 实施下一代干细胞疗法以治疗心力衰竭。这一点的意义 STTR将允许Cardiocreate，Inc。作为小型企业前进，朝着寻找一个目标的目标 可以在国际上使用的有效且安全的治疗心脏病治疗 熟练的制造业就业为美国公民，并为我们的美国推进了高科技的科学成就 研究社区。