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Derivation of proliferative islet1-positive cells during metamorphosis and wound response in Xenopus
Saki Umezawa1, Miho Miyakawa1, Takashi Yamaura1
1Department of Life Science, Faculty of Science, Rikkyo University, 3-34-1 Nishi-Ikebukuro, Toshima-ku, Tokyo, 171-8501, Japan.
Insights
Xenopus laevis islet1-positive cells are a key cellular resource for heart regeneration. These cells contribute to vascularization and the formation of new cardiomyocytes after injury.
Area of Science:
- Cardiovascular Biology
- Developmental Biology
- Regenerative Medicine
Background:
- Mammalian heart regeneration is limited after birth.
- Cardiac progenitor cells, including islet1-positive cells, do not typically contribute to mammalian cardiac repair.
- Lower vertebrates like Xenopus laevis exhibit lifelong cardiac regenerative capacity.
Purpose of the Study:
- To investigate the proliferative capacity of cardiac cells, particularly islet1-positive cells, in Xenopus laevis during development and after cardiac injury.
- To determine if islet1-positive cells serve as a cellular resource for cardiac regeneration in adult Xenopus laevis.
Main Methods:
- Immunohistochemistry to identify and quantify islet1-positive cells.
- Analysis of cell proliferation after metamorphosis and cardiac resection.
- Histological examination of the resection site.
- Vascular labeling using biotinylated dextran amine (BDA).
Main Results:
- Islet1-positive cells are abundant in the ventricle and retain high proliferative capacity post-metamorphosis, persisting for at least one year.
- Following cardiac resection, islet1-positive cells rapidly appear at the amputation site and proliferate significantly.
- Islet1-positive cells, especially in tropomyosin-negative regions, are associated with vascularization and contribute to the regeneration of tropomyosin-positive cardiomyocytes.
Conclusions:
- Islet1-positive cells in Xenopus laevis represent a crucial cellular resource for cardiac regeneration.
- These cells play a vital role in both vascularization and the generation of new cardiomyocytes post-injury.
- The findings highlight Xenopus laevis as a model for understanding cardiac regeneration mechanisms relevant to potential therapeutic strategies.
Abstract:
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.
