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

描述(由申请人提供)： 将成人成纤维细胞重新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引起了极大的兴奋。IPS细胞避免了围绕人类胚胎干细胞(HES)的伦理问题，也具有患者特异性和疾病特异性的潜力。然而，目前该领域仍处于初级阶段，iPS细胞衍生品的有效性、安全性和有效性仍存在重大担忧。这篇斯坦福-格拉德斯通关于“用于理解和治疗心脏病的IPS细胞”的论文将探讨以下方面： 具体目的1：利用非病毒微环质粒从成人脂肪基质细胞(HASCs)中培养出iPS细胞。 具体目的2：利用网络通路分析比较人脂肪基质细胞来源的诱导多能干细胞(HASC-iPS)和HES细胞。 具体目的3：通过mlRNA重编程方法显著提高HASC-iPS细胞的产量。 特定目的4：利用新的分子成像技术评估IPS细胞来源的心肌细胞(IPSC-CMS)在活体内的命运。 具体目的5：证明在心肌梗死模型中移植IPSC-CMS将有益地改善心肌的收缩能力、灌注量和存活能力。 为了解决这些问题，我们组建了一个跨学科调查团队。该团队在干细胞生物学、遗传学、microRNA、外科、大小动物模型、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.