Regenerative medicine: in vitro and in vivo models and the role of small-molecule compounds

Regenerative medicine, as a gospel for masses of incurable diseases, holds great promise for replacing damaged tissue and/or stimulating the organisms’ own repair mechanisms to replenish the damaged ones. One of the challenges in developing regenerative medicines is the lack of reliable and cost effective in vitro and in vivo models for assessing cell self-renewal and tissue regeneration.

Zebrafish, human embryonic carcinoma cells (EC cells) and human embryonic stem cells (hES cells) were developed in this project to explore the possible function and mechanism of a series of novel small molecules. Multiple techniques including in-situ hybridization, quantitative real-time PCR, fluorescence-activated cell sorting, RNAi high–throughput screening and kinase profiling, etc. were used to investigate the biological activities of these compounds in relevant cellular or animal models. Based on the data gained so far, it is believed that compound 672 is able to increase stem cell proliferation in vitro and zebrafish fin repair in vivo in ERK1-dependent manner, acting through interacting with insulin receptor substrate-1 (IRS-1). The other compound 689 was shown to accelerate the growth of stem cells and fin repair through preventing cell death by upregulating superoxide dismutase 2 (SOD2).