Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH, USA.
Stem Cells Transl Med. 2013 Jun;2(6):401-8. doi: 10.5966/sctm.2012-0185. Epub 2013 May 15.
Abdominal aortic aneurysms (AAAs) are potentially fatal conditions that are characterized by decreased flexibility of the aortic wall due to proteolytic loss of the structural matrix. This leads to their gradual weakening and ultimate rupture. Drug-based inhibition of proteolytic enzymes may provide a nonsurgical treatment alternative for growing AAAs, although it might at best be sufficient to slow their growth. Regenerative repair of disrupted elastic matrix is required if regression of AAAs to a healthy state is to be achieved. Terminally differentiated adult and diseased vascular cells are poorly capable of affecting such regenerative repair. In this context, stem cells and their smooth muscle cell-like derivatives may represent alternate cell sources for regenerative AAA cell therapies. This article examines the pros and cons of using different autologous stem cell sources for AAA therapy, the requirements they must fulfill to provide therapeutic benefit, and the current progress toward characterizing the cells' ability to synthesize elastin, assemble elastic matrix structures, and influence the regenerative potential of diseased vascular cell types. The article also provides a detailed perspective on the limitations, uncertainties, and challenges that will need to be overcome or circumvented to translate current strategies for stem cell use into clinically viable AAA therapies. These therapies will provide a much needed nonsurgical treatment option for the rapidly growing, high-risk, and vulnerable elderly demographic.
腹主动脉瘤 (AAA) 是一种潜在致命的疾病,其特征是由于结构基质的蛋白水解丢失导致主动脉壁的柔韧性降低。这导致它们逐渐变弱并最终破裂。基于药物的蛋白水解酶抑制可能为不断增大的 AAA 提供一种非手术治疗选择,尽管它最多只能足以减缓其生长。如果要使 AAA 恢复到健康状态,则需要对受损的弹性基质进行再生修复。终末分化的成年和患病血管细胞在影响这种再生修复方面能力很差。在这种情况下,干细胞及其平滑肌细胞样衍生物可能代表用于 AAA 细胞再生治疗的替代细胞来源。本文探讨了使用不同自体干细胞来源治疗 AAA 的优缺点、它们必须满足的要求才能提供治疗益处,以及目前对细胞合成弹性蛋白、组装弹性基质结构以及影响患病血管细胞类型的再生潜力的能力进行特征描述的进展。文章还详细探讨了在将当前的干细胞使用策略转化为临床可行的 AAA 治疗方法时需要克服或规避的局限性、不确定性和挑战。这些疗法将为快速增长、高风险和脆弱的老年人群提供急需的非手术治疗选择。