In mammalian hearts, cardiomyocytes retain a transient capacity to proliferate and regenerate following injury before birth, whereas they lose proliferative capacity immediately after birth. It has also been known that cardiac progenitor cells including islet1-positive cells do not contribute to the cardiac repair and regeneration in mammals. In contrast, hearts of zebrafish, amphibians and reptiles maintain a regenerative ability throughout life. Here, we analyzed proliferative capacity of cardiac cells during cardiac development and post-ventricular resection using Xenopus laevis, especially focusing on islet1. Immunohistochemical examination showed that islet1-positive cells were present in a wide range of the ventricle and maintained high dividing ability after metamorphosis. Interestingly, the islet1-positive cells were preserved even at 1 year after metamorphosis, some of which showed tropomyosin expression. To assess the possibility of islet1-positive cells as a cellular resource, islet1 response to cardiac resection was analyzed, using adult hearts of 3 months after metamorphosis. Transient gene activation of islet1 in apical region was detected within 1 day after amputation. Histological analyses revealed that islet1-positive cells appeared in the vicinity of resection plane at 1 day post-amputation (dpa) and increased at 3 dpa in both tropomyosin-positive and tropomyosin-negative regions. Vascular labeling analysis by biotinylated dextran amine (BDA) indicated that the islet1-positive cells in a tropomyosin-negative region were closely associated with cardiac vessels. Moreover, dividing ability at this time point was peaked. The resected region was healed with tropomyosin-positive cardiomyocytes until 3 months post-amputation. These results suggest a role of islet1-positive cells as a cellular resource for vascularization and cardiogenesis in Xenopus laevis.

在哺乳动物心脏中，心肌细胞保留了出生后受伤后增殖和再生的短暂能力，而它们在出生后立即丧失了增殖能力。还已知包括胰岛1阳性细胞在内的心脏祖细胞对哺乳动物的心脏修复和再生没有贡献。相反，斑马鱼，两栖动物和爬行动物的心脏在整个生命中都保持着再生能力。在这里，我们使用非洲爪蟾（Xenopus laevis）分析了心脏发育和心室切除后心脏细胞的增殖能力，尤其是islet1。免疫组织化学检查显示，胰岛1阳性细胞存在于广泛的脑室，并在变态后保持高分裂能力。有趣的是，胰岛1阳性细胞甚至在变态后1年就得以保存，其中一些表现出原肌球蛋白的表达。为了评估胰岛1阳性细胞作为细胞资源的可能性，使用变态后3个月的成年心脏，分析了胰岛1对心脏切除的反应。islet1的瞬时基因激活截肢后1天内检测到根尖区域的异常。组织学分析显示，在截肢后第1天（dpa），胰岛1阳性细胞出现在切除平面附近，在原肌球蛋白阳性和原肌球蛋白阴性区域，胰岛1阳性细胞在3 dpa时都增加。通过生物素化的葡聚糖胺（BDA）进行的血管标记分析表明，原肌球蛋白阴性区域中的islet1阳性细胞与心血管密切相关。此外，此时的分割能力达到峰值。切除的区域用原肌球蛋白阳性的心肌细胞治愈，直到截肢后3个月。这些结果表明胰岛1阳性细胞作为非洲爪蟾血管化和心脏发生的细胞资源的作用。