Novel Agents for the Proliferation of Stem Cells

干细胞增殖的新型药物

• 批准号: 7608957
• 负责人: CYNTHIA C. BAMDAD
• 金额: $ 18.13万
• 依托单位: MINERVA BIOTECHNOLOGIES CORPORATION
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7608957
• 关键词: Affinity; Antibodies; Arts; BFU-E; Binding; Biological Assay; Bone Marrow; Brain; Cell Cycle; Cell-Free System; Cells; Code; Condition; Conditioned Culture Media; Development; Diabetes Mellitus; Dimerization; Dose; Epithelial; Evaluation; Fibroblast Growth Factor 2; Fluorouracil; Government; Growth; Growth Factor; Growth Factor Receptors; Heart failure; Hematopoietic; Human; Human body; In Vitro; Kidney; Kinetics; Lead; Length; Ligands; Malignant Neoplasms; Measures; Membrane; Methods; Modeling; Molecular; Monoclonal Antibodies; Mucin-1 Staining Method; Mus; Mutation; Myocardium; NME1 gene; Numbers; Organ; Persons; Pluripotent Stem Cells; Population; Proliferating; Property; Proteins; Protocols documentation; Public Health; Purpose; Range; Reagent; Recovery; Reporting; Retinal Diseases; Signal Transduction; Solid Neoplasm; Spinal Cord; Spinal cord injury; Staining method; Stains; Stem cells; Surface; Testing; Therapeutic; Therapeutic Intervention; Thinking; Tissues; Undifferentiated; United States National Institutes of Health; WA09 Cell Line; Withdrawal; brain tissue; cancer cell; cell growth; cell type; chemotherapy; desire; dimer; embryonic stem cell; growth promoting activity; human embryonic stem cell; in vivo; mutant; neoplastic cell; novel; pluripotency; progenitor; rapid growth; receptor; repaired; research study; response; stem cell therapy; therapeutic target; tool

DESCRIPTION (provided by applicant): Pluripotent (undifferentiated) stem cells possess the ability to become virtually any cell type in the human body and therefore, in principal, could be used to replace damaged tissues in organs that have traditionally been thought not to have a significant potential for functional self-repair such as heart muscle, spinal cord, brain tissue and kidney. However, to implement these therapies, one must have the ability to identify, isolate and proliferate populations of pluripotent stem cells. The first problem is that current methods for identifying pluripotent stem cells are insufficient. We have identified a new marker of pluripotency that discriminates between two different cell types within a population that current methods identify as being all "pluripotent". Secondly, it is difficult to culture embryonic stem cells (ESCs) without initiating differentiation. Growing ESCs under current state of the art protocols will yield only 50-75% undifferentiated colonies. This is in large part due to the fact that they are grown over a layer of "feeder" cells which secrete poorly understood factors, some of which promote the growth of undifferentiated stem cells and others that undoubtedly trigger differentiation. Factors secreted by neighboring cells influence how pluripotent stem cells differentiate. For example, pluripotent stem cells can be influenced to differentiate into a particular cell type by growing them over tissues of the desired cell type. What is needed is a cell-free system for growing ESCs in which only discrete, well-characterized agents are added to drive their growth. We have succeeded in growing ESCs in a cell-free system by adding a single agent that activates a newly identified growth factor receptor on the surface of ESCs - conditioned media from feeder cells was not added. The resultant population was 100% pluripotent and was signaled to differentiate by the withdrawal of our novel agent. This is a major step toward understanding the molecular drivers that maintain pluripotency as well as those that initiate differentiation and will enable stem cell therapies that are currently out of reach. Thus the isolation and propagation of pure pools of pluripotent stem cells will be critical for therapeutic applications of stem cell therapy for the repair of brain and spinal cord injuries, diabetes, cardiac failure, retinopathies and further will enable a whole range of therapeutic interventions that are currently not possible. PUBLIC HEALTH RELEVANCE: Pluripotent (undifferentiated) stem cells possess the ability to become virtually any cell type in the human body and therefore, in principal, could be used to replace damaged tissues in organs that have traditionally been thought not to have a significant potential for functional self-repair such as heart muscle, spinal cord, brain tissue and kidney. However, to implement these therapies, one must have the ability to identify, isolate and proliferate populations of pluripotent stem cells. We have succeeded in growing ESCs in a cell-free system by adding a single agent that activates a newly identified growth factor receptor on the surface of ESCs - conditioned media from feeder cells was not added.

描述（由申请人提供）：多能（未分化的）干细胞具有成为人体中几乎任何细胞类型的能力，因此，可以用来代替传统上认为不具有功能性自我修复的器官中受损的组织，例如心脏肌肉，脊髓，脑组织和小子。但是，要实施这些疗法，必须具有鉴定，分离和扩增多能干细胞种群的能力。第一个问题是当前用于识别多能干细胞的方法不足。我们已经确定了一种新的多能性标记，该标记区分了当前方法识别为“多能”的种群中两种不同的细胞类型。其次，在不引发分化的情况下培养胚胎干细胞（ESC）是很难的。在目前的最新协议状态下，ESC的增长只能产生50-75％的未分化菌落。这在很大程度上是由于它们生长在一层“馈线”细胞上，这些细胞分泌了不足的因素，其中一些促进了未分化的干细胞的生长，而其他无疑却无疑会触发分化。相邻细胞分泌的因素会影响多能干细胞的分化。例如，多能干细胞可以通过在所需细胞类型的组织上种植在特定细胞类型中的影响。需要的是一种无细胞的系统，用于增长ESC，其中仅添加离散的，良好的代理以推动其生长。我们通过添加一种单个药剂来激活在ESCS表面上激活新鉴定的生长因子受体的单个药物，从而成功地增长了ESC，该药物未添加来自馈线细胞的调节培养基。最终的人群为100％多能，并通过我们的新型药物的撤离来发出信号。这是了解维持多能性的分子驱动因素以及启动分化并将实现当前无法触及的干细胞疗法的分子驱动因素的主要步骤。因此，多能干细胞的纯库的隔离和传播对于干细胞治疗在修复脑和脊髓损伤，糖尿病，心脏衰竭，视网膜病变方面的治疗应用至关重要至关重要。公共卫生相关性：多能（未分化的）干细胞具有几乎成为人体中任何细胞类型的能力，因此，可以用来替代传统上认为不具有功能性自我重复的器官中受损的组织，例如心脏肌肉，脊髓，脑组织和肾脏。但是，要实施这些疗法，必须具有鉴定，分离和扩增多能干细胞种群的能力。我们通过添加一种单个药剂来激活在ESCS表面上激活新鉴定的生长因子受体的单个药物，从而成功地增长了ESC，该药物未添加来自馈线细胞的调节培养基。