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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 虽然骨髓源性（BMD）细胞作为治疗实体的潜力有时可能被夸大，但它们可能会成为改善组织修复和血管生长的重要工具。 骨密度细胞疗法可以促进血管生成，并且可以通过刺激血管生成来减轻糖尿病的许多并发症。 BMD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。 我们不同意它对2型糖尿病患者是低风险的。 来自几个实验室的数据表明，自体BMD细胞疗法可能无效，实际上可能对某些糖尿病患者有害。 我们的最终目标是使BMD细胞疗法诱导血管生长成为所有2型糖尿病患者的一种选择。 我们将检验以下假设：1）来自2型糖尿病患者的BMD细胞亚群，其糖尿病和其他心血管危险因素得到良好控制，是血管生长的有效刺激物，和2）BMD细胞的促血管生成活性因糖尿病而减弱，并且当与共病结合时，使BMD细胞非血管生成或抗血管生成。 我们的目的是1）鉴定人2型糖尿病衍生的BMD细胞的子集和递送方法，其组合有效地刺激糖尿病小鼠中的血管生长;和2）确定诱导血管生长的自体BMD细胞疗法对于一些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.