Abstract
Natural bioactive materials provide an excellent pool of molecules for regenerative therapy. In the present study, we amputate portions of the arms of Archaster typicus starfish, extract and separate the active biomaterials, and compare the effects of each fraction on in vitro wound healing and in vivo lower jaw regeneration of zebrafish. Compared with crude extract, normal hexane fractions (NHFs) have a remarkable effect on cellular proliferation and collective migration, and exhibit fibroblast-like morphology, while methanol-water fractions (MWFs) increase cell size, cell-cell adhesion, and cell death. Relative to moderate mitochondrialand lysosomal aggregation in NHFs-cultured cells, MWFs-cultured cells contain more and bigger lysosomal accumulations and clump detachment. The in vivo zebrafish lower jaw regeneration model reveals that NHFs enhance blastema formation and vasculogenesis, while MWFs inhibit fibrogenesis and induce cellular transformation. Gene expression analyses indicate that NHFs and MWFs separately activate blastema-characteristic genes as well as those genes-related to autophagy, proteasome, and apoptosis either during cell scratch healing or ganciclovir-induced apoptosis. Our results suggest that bioactive compounds from NHFs and MWFs could induce blastema formation and remodeling, respectively, and prevent tissue overgrowth.
Highlights
The results consistently indicated that normal hexane fractions (NHFs) enhanced fibroblast-like cell proliferation and directional migration, while methanol-water fractions (MWFs) induced cytotoxic responses and cellular transformation
We address the extent to which starfish arm regeneration differs from zebrafish regeneration
In addition to blastema structure, wound sealing, wound healing, wound epidermis reconstitution, and epithelial/mesenchymal interconversions represent the basic processes of nearly complete healing in both zebrafish and starfish[2,7,22]
Summary
Investigation into the regenerative mechanisms and processes in starfish and zebrafish can facilitate our understanding of how these animals overcome the specific selection pressure to enhance tissue regeneration. A related question of whether starfish regeneration is compatible with zebrafish regeneration merits further study. To address these questions, we extend the use of the in vitro and in vivo model systems of zebrafish to the study of regenerative biomaterials. There is little information regarding tissue regeneration and the starfish-derived bioactive substances. We investigated the preparative isolation of active materials from the regenerating A. typicus starfish and evaluated their inhibitory and/or stimulatory effects on zebrafish cell lines and tissues. The present study offers an alternative, but promising, approach for future regenerative medicine
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