Safety Assessment of Pluripotent Stem Cell Therapy Using Nanotechnology

使用纳米技术的多能干细胞疗法的安全性评估

• 批准号: 8902262
• 负责人: Chunhui Xu
• 金额: $ 19.21万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-15 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8902262
• 关键词: Biological; Biological Assay; Cardiac; Cardiac Myocytes; Cell Differentiation process; Cell Therapy; Cells; Clinical; Complex; Development; Diagnostic; Disease; Environment; Evaluation; Fingerprint; Flow Cytometry; Gene Expression; Genes; Health; Heart failure; Human; In Vitro; Molecular; Molecular Profiling; Nanotechnology; Outcome; Pathway interactions; Pattern; Pluripotent Stem Cells; Population; Preparation; Proliferating; Raman Spectrum Analysis; Regenerative Medicine; Residual state; Risk; Safety; Source; Specificity; Staging; Stem cells; Surface; Technology; Teratoma; Therapeutic Uses; Translations; Transplantation; Tumorigenicity; Undifferentiated; base; cell preparation; cell type; clinical application; design; human embryonic stem cell; in vivo; induced pluripotent stem cell; meetings; nanoparticle; novel; novel strategies; prevent; single molecule; stem cell therapy; tool; tumor

DESCRIPTION (provided by applicant): Human pluripotent stem cells are promising and potentially unlimited cell source for regenerative medicine; however, tumor formation is of major concern for cell therapy with pluripotent stem cells. Residual undifferentiated stem cells in preparations of stem cell derivatives, including cardiomyocyte differentiation cultures, have potential to proliferate and form teratoma upon transplantation, posing a major hurdle for safe cell therapy. Careful assessment of differentiation cultures and development of strategies to remove undifferentiated stem cells will facilitate qualification of final stem cell products for therapeutic use. In this study, we propose to develop sensitive, nanotechnology-based assays to detect residual undifferentiated cells, characterize cardiomyocyte differentiation cultures at various stages for their propensities to form teratomas, and evaluate strategies to selectively remove residual undifferentiated cells. Technology established in this study will be valuable for the development of novel cell therapy using human pluripotent stem cells.

描述（由申请人提供）：人类多能干细胞是再生医学中有前途和潜在无限的细胞来源；然而，肿瘤的形成是多能干细胞细胞治疗的主要问题。干细胞衍生物制剂中残留的未分化干细胞，包括心肌细胞分化培养物，在移植后具有增殖和形成畸胎瘤的潜力，这是安全细胞治疗的主要障碍。仔细评估分化培养和开发去除未分化干细胞的策略将有助于最终用于治疗用途的干细胞产品的鉴定。在这项研究中，我们建议开发敏感的、基于纳米技术的检测方法来检测残留的未分化细胞，表征不同阶段心肌细胞分化培养物形成畸胎瘤的倾向，并评估选择性去除残留未分化细胞的策略。在这项研究中建立的技术将对开发利用人类多能干细胞的新型细胞疗法有价值。

项目成果

Cryopreservation of Human Pluripotent Stem Cell-Derived Cardiomyocytes: Strategies, Challenges, and Future Directions.

人类多能干细胞来源的心肌细胞的冷冻保存：策略、挑战和未来方向。

• DOI: 10.1007/978-3-319-45457-3_10
• 发表时间: 2016
• 期刊: Advances in experimental medicine and biology
• 作者: Preininger,MarcelaK;Singh,Monalisa;Xu,Chunhui
• 通讯作者: Xu,Chunhui

Downregulation of LGR5 Expression Inhibits Cardiomyocyte Differentiation and Potentiates Endothelial Differentiation from Human Pluripotent Stem Cells.

• DOI: 10.1016/j.stemcr.2017.07.006
• 发表时间: 2017-08-08
• 期刊: Stem cell reports
• 影响因子: 5.9
• 作者: Jha R;Singh M;Wu Q;Gentillon C;Preininger MK;Xu C
• 通讯作者: Xu C

A human pluripotent stem cell model of catecholaminergic polymorphic ventricular tachycardia recapitulates patient-specific drug responses.

• DOI: 10.1242/dmm.026823
• 发表时间: 2016-09-01
• 期刊: Disease models & mechanisms
• 影响因子: 4.3
• 作者: Preininger MK;Jha R;Maxwell JT;Wu Q;Singh M;Wang B;Dalal A;Mceachin ZT;Rossoll W;Hales CM;Fischbach PS;Wagner MB;Xu C
• 通讯作者: Xu C