Harnessing Adult Stem Cells for Cardiac Regeneration

利用成体干细胞促进心脏再生

• 批准号: 7663863
• 负责人: Ronglih Liao
• 金额: $ 43万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7663863
• 关键词: Abbreviations; Adenomatous Polyposis Coli; Adopted; Adult; Area; Biochemical; Biological; Biomedical Engineering; Bone Marrow; Bone Marrow Stem Cell; Bone Morphogenetic Proteins; CSNK1A1 gene; Calcium; Calmodulin; Cardiac; Cardiac Myocytes; Cardiovascular system; Cell Proliferation; Cells; Coculture Techniques; Coupling; Data; Dimethylsiloxanes; Dyes; Fluorescence-Activated Cell Sorting; Genetic Transcription; Glycogen Synthase Kinase 3; Goals; Green Fluorescent Proteins; Guanosine Triphosphate; Heart; Heterotrimeric GTP-Binding Proteins; Home environment; Homing; Immunophenotyping; In Vitro; Injury; Knowledge; LDL-Receptor Related Protein 1; Laboratories; Link; MAPK8 gene; Mediating; Mediator of activation protein; Methodology; Modeling; Molecular; Mus; Myocardial; Myocardial Infarction; Myocardium; N-terminal; Natural regeneration; Pathway interactions; Pattern; Pharmaceutical Preparations; Phospholipase C; Phosphotransferases; Population; Process; Protein Kinase C; Proteins; Research Personnel; Side; Signal Pathway; Signal Transduction; Stem cells; TCF Transcription Factor; Technology; Therapeutic; Therapeutic Uses; Tissues; Work; adult stem cell; casein kinase; implantation; in vivo; injured; interdisciplinary approach; malignant breast neoplasm; novel; paracrine; phosphoric diester hydrolase; programs; repaired; research study; rho GTP-Binding Proteins; self-renewal; stem cell biology; stem cell population

DESCRIPTION (provided by applicant): Our understanding of stem cell biology, especially in regards to its use for therapeutic cardiovascular regeneration, has continued at a staggering pace. Over the past few years, the identification of endogenous cardiac stem cells has raised the exciting possibility of harnessing these cells for cardiac repair. Recently, our laboratory has observed the existence of a cardiac progenitor cell population. These so termed cardiac side-population (CSP) cells, identified in adult hearts by their distinct Hoechst dye efflux pattern, represent a distinct cardiac progenitor cell population, capable of both biochemical and, more importantly, functional cardiomyogenic differentiation through a process mediated by coupling with adult cardiomyocytes. Moreover, after myocardial infarction (Ml), CSP cells are acutely depleted, and are restored through self-renewal of endogenous CSP cells and homing of extra-cardiac bone marrow-derived side population (BMSP) stem cells. Following homing to the injured hearts, BMSP adopt an immunophenotype similar to endogenous CSP cells. As such, utilizing a multidisciplinary approach of in-vitro and in-vivo methodologies, the main goal of this proposal is to delineate the signaling pathways regulating the proliferation and differentiation of CSP cells. Additionally, we will determine the functional significance of BMSP cell homing to injured myocardium, with the ultimate goal of harnessing these adult stem cells for physiologically significant cardiac regeneration.

描述（由申请人提供）：我们对干细胞生物学的理解，特别是在其用于治疗性心血管再生方面的理解，一直在以惊人的速度继续进行。在过去的几年中，内源性心脏干细胞的鉴定提出了利用这些细胞进行心脏修复的令人兴奋的可能性。最近，我们的实验室观察到心脏祖细胞群的存在。这些所谓的心脏侧群 (CSP) 细胞在成人心脏中通过其独特的 Hoechst 染料流出模式进行识别，代表了独特的心脏祖细胞群，能够通过偶联介导的过程进行生化分化，更重要的是能够进行功能性心肌分化。与成人心肌细胞。此外，在心肌梗塞(M1)之后，CSP细胞急剧耗尽，并且通过内源CSP细胞的自我更新和心外骨髓衍生侧群(BMSP)干细胞的归巢而恢复。归巢至受伤心脏后，BMSP 采用与内源性 CSP 细胞相似的免疫表型。因此，利用体外和体内方法学的多学科方法，该提案的主要目标是描绘调节 CSP 细胞增殖和分化的信号通路。此外，我们将确定 BMSP 细胞归巢至受损心肌的功能意义，最终目标是利用这些成体干细胞进行具有生理意义的心脏再生。