Clinically Relevant CiPS Cell Lines

临床相关 CiPS 细胞系

• 批准号: 7672118
• 负责人: Babak Esmaeli-Azad
• 金额: $ 24.03万
• 依托单位: DNAMICROARRAY, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2011-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7672118
• 关键词: 3-Dimensional; Address; Adult; Antibodies; Biochemical; Biological; Biological Assay; Biological Markers; Cell Culture Techniques; Cell Line; Cell Therapy; Cells; Chemicals; Clinic; Data; Derivation procedure; Dermal; Development; Disease; Epigenetic Process; Event; Fibroblasts; Foundations; Generations; Genetic Induction; Genetic Screening; Goals; Housing; Human; Hydrogels; In Vitro; Injury; Libraries; Life; Methodology; Molecular; Mutation; Nucleic Acids; Patients; Pharmaceutical Chemistry; Phase; Phase II Clinical Trials; Play; Preparation; Procedures; Process; Proteins; Protocols documentation; Research; Role; SCID Mice; Screening procedure; Signal Transduction Pathway; Skin; Somatic Cell; Speed; Stochastic Processes; Structure; System; Techniques; Technology; Translations; base; cellular transduction; chemical genetics; clinically relevant; design; human stem cells; improved; in vivo Model; induced pluripotent stem cell; mouse model; non-genetic; pluripotency; public health relevance; research and development; self-renewal; small molecule; stem; tissue regeneration; tool; transcription factor

DESCRIPTION (provided by applicant): Studies outlined in this proposal are designed to provide a platform for research and development of new clinically translatable iPS cell lines specifically addressing the shortcomings of current iPS procedures that impede potential translation of this approach for use in the clinic. Induction of pluripotent status in somatic cells by directed reprogramming in-vitro, induced pluripotent stem (iPS) cells, is of great potential significance for the generation of disease and patient specific cell lines and cell therapy (1,2,3). Although quite promising and revolutionary, to date iPS techniques share several main shortcomings which collectively impede potential translation of this approach for use in the clinic. Our long-term goal (Phase II and beyond) is to develop, tools, and cell lines that allow translation of iPS cells into therapies for the clinic. The specific hypothesis behind the proposed research is that improved more clinically translatable iPS procedures such as the use of small molecule inducers of iPS signal transduction pathways, can be devised streamlining development of "clinically translatable" human iPS cell lines. Accomplishing the specific aims outlined in this proposal will provide the foundation required to assess the possibility of generation of Human iPS cell lines by clinically relevant methodologies, eliminating the current impediments for translation of iPS cells into the clinic. In this Phase I feasibility demonstration project we plan to further characterize "pluripotency" of previously developed human chemically induced iPS (CiPSTM) cells at the molecular, cellular levels including studies in SCID mouse models. Furthermore, in preparation for further refinements of the CiPS methodology (Phase II), we will adapt their cultivation and derivation to the Cell Matrix ArraysTM (http://www.dnamicroarray.com/cell_matrix_arrays.htm) PUBLIC HEALTH RELEVANCE: Studies outlined in this proposal are designed to provide a platform for research and development of new clinically translatable induced pluripotent stem (iPS) cell lines specifically addressing the shortcomings of current iPS procedures that impede potential translation of this approach for use in the clinic. We propose to eliminate the need for genetic alterations of iPS cells, increase the efficiency of the process, and develop clinically applicable identification methodologies for iPS cells. Human iPS cells hold great potential for the generation of disease and patient specific cell lines, cell therapies and tissue regeneration, benefiting the current unmet need for patient customized cell lines that could be used for treatment of life threatening diseases and injuries. Accomplishing the specific aims outlined in this proposal will provide the foundation required to assess the possibility of generation of Human iPS cell lines by clinically relevant methodologies, eliminating the current impediments for translation of iPS cell lines into the clinic.

描述（由申请人提供）：本提案中概述的研究旨在为新的临床可转化 iPS 细胞系的研究和开发提供一个平台，专门解决当前 iPS 程序的缺点，这些缺点阻碍了该方法在临床中的潜在转化。通过体外定向重编程诱导多能干 (iPS) 细胞诱导体细胞的多能状态，对于疾病和患者特异性细胞系的产生以及细胞治疗具有重要的潜在意义 (1,2,3)。尽管非常有前途且具有革命性，但迄今为止 iPS 技术存在几个主要缺点，这些缺点共同阻碍了这种方法在临床中的潜在转化。我们的长期目标（第二阶段及以后）是开发能够将 iPS 细胞转化为临床疗法的工具和细胞系。拟议研究背后的具体假设是，可以设计改进更多临床可转化的 iPS 程序，例如使用 iPS 信号转导途径的小分子诱导剂，以简化“临床可转化”人类 iPS 细胞系的开发。实现该提案中概述的具体目标将为评估通过临床相关方法产生人类 iPS 细胞系的可能性提供所需的基础，从而消除当前将 iPS 细胞转化为临床的障碍。在这一第一阶段可行性论证项目中，我们计划在分子、细胞水平上进一步表征先前开发的人类化学诱导 iPS (CiPSTM) 细胞的“多能性”，包括 SCID 小鼠模型的研究。此外，为了进一步完善 CiPS 方法（第二阶段），我们将调整其培养和衍生以适应 Cell Matrix ArraysTM (http://www.dnamicroarray.com/cell_matrix_arrays.htm) 公共卫生相关性：中概述的研究该提案旨在为新的临床可转化诱导多能干（iPS）细胞系的研究和开发提供一个平台，专门解决当前 iPS 程序的缺点阻碍这种方法在临床中使用的潜在转化。我们建议消除对 iPS 细胞进行遗传改变的需要，提高该过程的效率，并开发临床适用的 iPS 细胞鉴定方法。人类 iPS 细胞在产生疾病和患者特异性细胞系、细胞治疗和组织再生方面具有巨大潜力，有利于当前对可用于治疗危及生命的疾病和损伤的患者定制细胞系的未满足的需求。实现该提案中概述的具体目标将为评估通过临床相关方法产生人类 iPS 细胞系的可能性提供所需的基础，消除当前将 iPS 细胞系转化为临床的障碍。