BONE MARROW-DERIVED CELL BASED THERAPY FOR TYPE 2 DIABETIC PATIENTS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 尽管骨髓来源的(BMD)细胞作为治疗实体的潜力有时可能被夸大，但它们很可能成为改善组织修复和血管生长的重要工具。骨密度细胞治疗可以促进血管生成，糖尿病的许多并发症可以通过刺激新生血管来缓解。骨密度细胞的临床试验已经取得了进展，因为它通常被认为是一种低风险的治疗方法。我们不同意这对2型糖尿病患者来说是低风险的。来自几个实验室的数据表明，自体BMD细胞疗法可能并不有效，实际上可能对一些糖尿病患者有害。我们的最终目标是使骨密度细胞疗法成为所有2型糖尿病患者的一种选择，以诱导血管生长。我们将测试以下假设：1)糖尿病和其他心血管危险因素得到很好控制的2型糖尿病患者的一部分BMD细胞是血管生长的有力刺激因素，2)糖尿病使BMD细胞的促血管生成活性减弱，当合并疾病时，BMD细胞使BMD细胞无血管生成或抗血管生成。我们的目标是1)确定人类2型糖尿病来源的BMD细胞的子集和一种联合有效地刺激糖尿病小鼠血管生长的输送方法；2)确定自体BMD细胞疗法诱导血管生长对某些2型糖尿病患者是否无效或不安全。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Though the potential of bone marrow-derived (BMD) cells as a therapeutic entity may be overstated at times, they will likely become an important tool for improving tissue repair and vascular growth. BMD cell therapy can promote angiogenesis, and many complications of diabetes could be mitigated by stimulation of neovascularization. Clinical trials with BMD cells have moved forward, because it has generally been perceived as a low risk therapy. We do not agree that it is low-risk for type 2 diabetic patients. Data from several laboratories suggest that autologous BMD cell therapy may not be effective and could actually be harmful in some diabetic patients. Our ultimate goal is to make BMD cell therapy to induce vascular growth an option for all type 2 diabetic patients. We will test the hypotheses that 1) a subset of BMD cells from type 2 diabetic patients, whose diabetes, and other cardiovascular risk factors are well controlled, are potent stimulators of vascular growth, and 2) the pro-angiogenic activity of BMD cells is diminished by diabetes, and when coupled with co-morbidities, renders BMD cells non- or anti-angiogenic. Our aims are to 1) identify a subset of human type 2 diabetic-derived BMD cells and a method of delivery that in combination potently stimulate vascular growth in diabetic mice; and 2) determine if autologous BMD cell therapy to induced vascular growth may be ineffective or unsafe for some type 2 diabetic patients.