Induced pluripotent stem cells in the understanding and treatment of heart diseas

描述（由申请人提供）： 成年人成纤维细胞重编程为诱导多能干细胞（iPS）在再生医学和干细胞生物学领域产生了重大的兴奋。IPS细胞避免了围绕人类胚胎干细胞（hES）的伦理问题，并且还具有患者特异性和疾病特异性的潜力。然而，目前该领域仍处于起步阶段，并且仍然存在对基于iPS细胞的衍生物的效率、安全性和功效的重大担忧。这斯坦福-格莱斯顿porcampus“IPS细胞的理解和治疗心脏病”将调查以下方面： 具体目的1：使用非病毒小环质粒从成人脂肪基质细胞（hASC）产生iPS细胞。 具体目的2：使用网络通路分析比较人脂肪基质细胞衍生的诱导多能干细胞（hASC-iPS）细胞和hES细胞。 具体目标3：通过mlRNA重编程方法显著提高hASC-iPS细胞的产量。 具体目的4：使用新型分子成像技术评估IPS细胞衍生的心肌细胞（iPSC-CM）的体内命运。 具体目标五：证明在梗死心脏模型中移植iPSC-CM将导致心脏收缩力、灌注和存活力的有益改善。 为了解决这些问题，我们组建了一个跨学科的研究团队。该团队在干细胞生物学、遗传学、microRNA、外科手术、小型和大型动物模型、免疫学、分子成像和生物信息学等领域拥有广泛的专业知识。重要的是，这个团队已经有了丰富的合作历史。因此，我们有信心在未来7年内取得重大进展，将转化为基于iPS细胞的临床疗法。

DESCRIPTION (provided by applicant): Reprogramming of adult human fibroblasts into induced pluripotent stem (iPS) cells has generated significant excitement in the fields of regenerative medicine and stem cell biology. IPS cells avoid the ethical issues surrounding human embryonic stem (hES) cells, and also have the potential for being patient- and diseasespecific. However, at present the field is still in its infancy and significant concerns still exist over the efficiency, safety, and efficacy of iPS cell-based derivatives. This Stanford-Gladstone porposal on "IPS Cells for the Understanding and Treatment of Heart Disease" will investigate the following aspects: Specific Aim 1: To generate iPS cells from adult human adipose stromal cells (hASCs) using non-viral minicircle plasmids. Specific Aim 2: To compare human adipose stromal cell-derived induced pluripotent stem (hASC-iPS) cells and hES cells using network pathway analyses. Specific Aim 3: To significantly enhance the yield of hASC-iPS cells by mlRNA reprogramming approach. Specific Aim 4: To assess the fate of IPS cell-derived cardiomyocytes (iPSC-CMs) in vivo using novel molecular imaging technology. Specific Aim 5: To demonstrate that transplantation of iPSC-CMs in an infarcted heart model will lead to beneficial improvements in cardiac contractility, perfusion, and viability. To tackle these questions, we have assembled a team of interdisciplinary investigators. This team has broad expertise in areas such as stem cell biology, genetics, microRNA, surgery, small & large animal models, immunology, molecular imaging, and bioinformatics. Importantly, this team already has a rich history of collaborations already. Thus, we are confident that significant advances can be made over the next 7 years that will translate into iPS cell-based clinical therapies.