Orlic Donald, Hill Jonathan M, Arai Andrew E
Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Md 20892-4442, USA.
Circ Res. 2002 Dec 13;91(12):1092-102. doi: 10.1161/01.res.0000046045.00846.b0.
Stem cells are being investigated for their potential use in regenerative medicine. A series of remarkable studies suggested that adult stem cells undergo novel patterns of development by a process referred to as transdifferentiation or plasticity. These observations fueled an exciting period of discovery and high expectations followed by controversy that emerged from data suggesting cell-cell fusion as an alternate interpretation for transdifferentiation. However, data supporting stem cell plasticity are extensive and cannot be easily dismissed. Myocardial regeneration is perhaps the most widely studied and debated example of stem cell plasticity. Early reports from animal and clinical investigations disagree on the extent of myocardial renewal in adults, but evidence indicates that cardiomyocytes are generated in what was previously considered a postmitotic organ. On the basis of postmortem microscopic analysis, it is proposed that renewal is achieved by stem cells that infiltrate normal and infarcted myocardium. To further understand the role of stem cells in regeneration, it is incumbent on us to develop instrumentation and technologies to monitor myocardial repair over time in large animal models. This may be achieved by tracking labeled stem cells as they migrate into myocardial infarctions. In addition, we must begin to identify the environmental cues that are needed for stem cell trafficking and we must define the genetic and cellular mechanisms that initiate transdifferentiation. Only then will we be able to regulate this process and begin to realize the full potential of stem cells in regenerative medicine.
干细胞因其在再生医学中的潜在用途而受到研究。一系列引人注目的研究表明，成体干细胞通过一种称为转分化或可塑性的过程经历新的发育模式。这些观察结果引发了一个令人兴奋的发现时期，并带来了很高的期望，随后出现了争议，因为有数据表明细胞 - 细胞融合是转分化的另一种解释。然而，支持干细胞可塑性的数据非常广泛，不容易被忽视。心肌再生可能是干细胞可塑性研究最广泛且争议最大的例子。动物和临床研究的早期报告在成人心肌更新程度上存在分歧，但有证据表明心肌细胞是在以前被认为是有丝分裂后器官中产生的。基于尸检显微镜分析，有人提出更新是由浸润正常和梗死心肌的干细胞实现的。为了进一步了解干细胞在再生中的作用，我们有责任开发仪器和技术，以便在大型动物模型中随时间监测心肌修复情况。这可以通过追踪标记的干细胞迁移到心肌梗死区域来实现。此外，我们必须开始确定干细胞迁移所需的环境信号，并且我们必须定义启动转分化的遗传和细胞机制。只有这样，我们才能调节这个过程，并开始实现干细胞在再生医学中的全部潜力。
