Schächinger Volker, Zeiher Andreas M
J.W. Goethe University, Frankfurt, Germany.
J Am Soc Nephrol. 2005 Mar;16 Suppl 1:S2-6. doi: 10.1681/asn.2004110971.
The traditional view that organs have only limited regenerative capacity has been challenged in recent years as adult bone marrow stem cells as well circulating progenitor cells have been identified to retain the plasticity to participate in neovascularization, a process so far believed not to be possible after birth. An organ that is damaged by ischemia causes the release of cytokines; these act via the flowing blood and stimulate the bone marrow, which then mobilizes progenitor cells to the blood and directs them to adhere to and migrate into the damaged organ. Thus, these progenitor cells most likely constitute a natural repair mechanism that counteracts degenerative or aging processes. On the basis of encouraging experimental data, first clinical trials have been established to demonstrate the safety and the feasibility of progenitor cell therapy in case of peripheral artery disease or myocardial infarction. Trials investigating injection of bone marrow or circulating progenitor cells into the coronary artery after an acute myocardial infarction not only demonstrates safety of the procedure but also gave hints toward efficacy. Nevertheless, these findings have to be validated by subsequent larger, prospective, randomized, controlled trials. There are also potential topics in nephrology, where modification of progenitor cell activity might be of benefit, such as renal ischemic disease, glomerular disease, and renal transplant vasculopathy. Finding a way to integrate the principle of progenitor cell action into therapeutic efforts might provide a completely new therapeutic strategy that not only attempts to retard disease progression but furthermore targets to regenerate damaged organs.
传统观点认为器官的再生能力有限，但近年来这一观点受到了挑战，因为已发现成年骨髓干细胞以及循环祖细胞具有可塑性，能够参与新生血管形成，而这一过程迄今被认为在出生后是不可能发生的。因缺血而受损的器官会释放细胞因子；这些细胞因子通过流动的血液起作用并刺激骨髓，骨髓随后将祖细胞动员到血液中，并引导它们黏附并迁移到受损器官。因此，这些祖细胞很可能构成一种天然的修复机制，以对抗退行性或衰老过程。基于令人鼓舞的实验数据，已经开展了首批临床试验，以证明祖细胞疗法在治疗外周动脉疾病或心肌梗死时的安全性和可行性。在急性心肌梗死后将骨髓或循环祖细胞注入冠状动脉的试验不仅证明了该操作的安全性，还暗示了其有效性。然而，这些发现必须通过后续更大规模、前瞻性、随机、对照试验来验证。在肾脏病学领域也存在一些潜在的课题，其中改变祖细胞活性可能有益，如肾缺血性疾病、肾小球疾病和肾移植血管病变。找到一种将祖细胞作用原理整合到治疗措施中的方法，可能会提供一种全新的治疗策略，这种策略不仅试图延缓疾病进展，而且旨在使受损器官再生。
