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以使该疗法真正安全和有效。我们 公司名称：ZeroCreate，Inc.率先使用基因工程来提高再生能力， 预期用于自体治疗利用的人心脏祖细胞（CPC）的潜力。CPCs 支持心肌修复，通过减少疤痕大小和增加 心输出量Pim-1是一种在CPC中发现的内源性组成型激活酶， 心肌对应激或病理损伤的反应。Pim-1上调通过以下途径增强细胞存活 介导CPC库的转录、细胞生长、增殖、存活和扩增。我们的遗产 对Pim-1生物学的十年研究随着显着的再生效果的展示而达到高潮 通过过继转移的人Pim-1介导，在啮齿动物和猪模型中， 相对于未修饰的CPC、骨髓干细胞和间充质干细胞，改善心脏性能 细胞我们对人Pim-1增强型CPC的研究也证明了衰老对细胞周期的逆转作用。 人CPC，如衰老标志物的下调，端粒长度和线粒体长度的增加， 活性和增殖的增强。自体Pim-1增强心脏的技术 祖细胞（Progenitor Cells）是心力衰竭的一种新的有效治疗方法， 改善我们社会的健康、长寿和福祉。EARTHENHANCERS ™有潜力提供一种 潜在的治疗和治愈心血管疾病，特别是心力衰竭，这是领先的 死亡原因在美国和平等地影响男性和女性的所有种族和种族。这 该提案代表了十年来高水平机械生物学研究的趋同发展 再加上再生医学解决方案的创业实施， 走向临床应用。在本第1阶段STTR提案中，重点是完成 通过FDA所需的致瘤性和遗传毒性评估组合进行体外安全性分析 强制IND批准。第一阶段的目标是产生FDA要求的第一组测试结果 以评估EARTHQUEENCERS ™的安全性。这个STTR的创新在于 实施下一代干细胞疗法治疗心力衰竭。其意义 STTR将允许ToshCreate，Inc.作为一个小企业，朝着找到一个 有效和安全的心脏病治疗方法，可在国际上使用， 为美国公民提供熟练的制造业工作，并为我们的美国推进高科技科学成就 研究社区。