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

项目总结 心肌再生疗法有望彻底改变治疗心力衰竭的方式，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 心脏创造公司率先使用基因工程来增强再生能力 人类心脏祖细胞(CPC)用于自身治疗的潜力。CPCS 通过减少疤痕大小和增加疤痕面积来支持心肌修复和改善心功能 心输出量。PIM-1是一种在CPC中发现的内源性结构性激活酶，在 心肌对应激或病理损伤的反应。PIM-1上调通过提高细胞存活率 调节CPC池的转录、细胞生长、增殖、存活和扩张。我们留下了超过一年的遗产 对Pim-1生物学十年的研究达到高潮，展示了显著的再生效应 过继转导的人Pim-1增强啮齿动物和猪模型的CPC 与未修饰的CPC、骨髓干细胞和间充质干细胞相比，心功能得到改善 细胞。我们对人Pim-1增强的CPC的研究也表明，衰老对 人类CPC，如下调衰老标志物，增加端粒长度和线粒体 活性和增殖能力的增强。应用自体Pim-1增强心脏的技术 祖细胞(心脏增强剂™)代表了一种新的有效的心力衰竭治疗方法，导致 改善我们社会的健康、长寿和福祉。心脏增强剂™有可能提供 心血管疾病的潜在治疗和治愈，尤其是心力衰竭，这是领先的 在美国是死因，对所有族裔和种族的男性和女性都有同样的影响。这 该提议代表了十年来高水平机械生物学研究的汇聚演变 再加上从实验室走出来的再生医学解决方案的企业化实施 走向临床环境的实施。在此第1阶段的STTR建议书中，重点将是在 FDA需要通过致瘤性和遗传毒性评估相结合的体外安全性分析 授权的IND审批。第一阶段的目标是生成FDA要求的第一组测试结果 评价心脏增强剂™的安全性。这一STTR的创新之处在于走向 实施下一代干细胞疗法治疗心力衰竭。这件事的意义 STTR将使HearoCreate，Inc.作为一家小企业向前迈进，朝着找到一个 可在国际上使用的有效和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就业机会，促进我们美国的高科技科技成果 研究社区。

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.