Differentiating Bone Marrow Stem Cells To Cure Diabetes

分化骨髓干细胞来治愈糖尿病

• 批准号: 6444413
• 负责人: VIJAYAKUMAR K RAMIYA
• 金额: $ 9.95万
• 依托单位: IXION BIOTECHNOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-15 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6444413
• 关键词: CD34 molecule; cell differentiation; cell population study; developmental genetics; hematopoietic stem cells; insulin dependent diabetes mellitus; mesenchyme; pancreatic islet transplantation; pancreatic islets; secretion; stem cells; tissue /cell culture

DESCRIPTION (Scanned from the Applicant's Abstract): Type 1 diabetes is a polygenic, chronic metabolic disease characterized by the progressive ablation of insulin-producing beta cells by autoimmunity. Regular insulin injections do not maintain blood glucose near normal levels at all times and consequently patients develop serious secondary clinical complications. While pancreatic and islet transplantations consistently establish euglycemic states and significantly reduce long-term complications, availability of the grafts is severely limited. Thus, there is an urgency to develop a beta cell/islet replacement therapy for Type 1 diabetic patients. The mammalian hematopoietic stem cells (HSCs) produce at least 8 distinct lineages of mature blood cells while mesenchymal stem cells (MSCs) produce multiple lineages of mature cells. The wealth of information on the growth and differentiation of these stem cells is vast, and purified HSCs are routinely used in the clinical setting and both HSCs and MSCs are commercially available for research purposes. Thus, investigating the feasibility of differentiating human HSCs and MSCs into pancreatic pathway will be of immense importance in curing Type 1 diabetes, and in the realization of autologous stem cell-derived insulin producing cell/islets for implantation. In this SBIR Phase I proposal, we will specifically: (1) characterize human bone marrow derived CD34+ HSCs and CD34-MSCs for the expression of developmental genes involved in the generation of islets/pancreas following treatments with various factors in vitro; and (2) determine the functional capability of the differentiated cells in vitro. A successful completion of the Phase I study will lay the foundation for a more detailed Phase II grant proposal that will involve in vivo functional studies in diabetic animal models. PROPOSED COMMERCIAL APPLICATION: This research project has the potential to produce glucose-responsive insulin producing cells/islets for implantion into every single insulin?dependent Type 1 & 2 diabetics. All that would be required from the individuals is their peripheral blood, or bone marrow samples. Also, cells that are at different stages of differentiation can be used for drug discovery research related to mesenchymal and pancreatic systems.

描述（从申请人的摘要扫描）：1型糖尿病是一种 以进行性消融为特征的多基因慢性代谢性疾病 产生胰岛素的β细胞。定期注射胰岛素 不能始终保持血糖接近正常水平， 患者出现严重的继发性临床并发症。虽然胰腺和 胰岛移植始终建立血糖正常状态， 显著减少长期并发症，移植物的可用性 严格限制。因此，迫切需要开发β细胞/胰岛 1型糖尿病患者的替代疗法。哺乳动物造血系统 干细胞（HSC）产生至少8种不同的成熟血细胞谱系 而间充质干细胞（MSC）产生多种成熟细胞谱系。 关于这些干细胞的生长和分化的丰富信息 是巨大的，纯化的HSC通常用于临床环境， HSC和MSC可商购获得用于研究目的。因此，在本发明中， 研究将人HSC和MSC分化为 胰腺途径将在治疗1型糖尿病方面具有巨大的重要性， 在实现自体干细胞衍生的胰岛素产生中， 用于植入的细胞/胰岛。在SBIR第一阶段提案中，我们将 具体地：（1）表征人骨髓来源CD 34 + HSC， CD 34-MSCs用于表达参与生成的发育基因 在体外用各种因子处理后的胰岛/胰腺;和（2） 体外测定分化细胞的功能能力。一 第一阶段研究的成功完成，将为未来一段更长的 详细的第二阶段拨款建议，将涉及体内功能研究 在糖尿病动物模型中。 拟定商业应用： 该研究项目有可能产生葡萄糖反应性胰岛素产生细胞/胰岛，用于分泌每一种胰岛素？依赖型1和2型糖尿病患者。所有需要从个人是他们的外周血，或骨髓样本。此外，处于不同分化阶段的细胞可用于与间充质和胰腺系统相关的药物发现研究。