The first problem that needs to be solved when regenerative medicine enters the clinical application is how to obtain a large number of safe and reliable human embryonic stem cells (hES) that can be transplanted into patients, and the main challenge is to develop a continuous culture and maintenance of clinical grade stem cells The best cultivation conditions.

Standard culture systems usually use mouse trophoblast cells and medium containing bovine serum to culture and maintain hES cells. However, this medium based on animal products may contaminate the cells. And because it is difficult to carry out accurate quality control, there may be some unnecessary differences in each batch of culture medium.

Recently, a scientific research team composed of stem cell biologists and engineers at the University of California, Los Angeles has found an optimal solution to combine some small molecule inhibitors at the optimal concentration, and proved that it can be used without trophoblasts and serum. Long-term cultivation and maintenance of hES cells. These small molecule inhibitors were efficiently selected by researchers using an innovative feedback control system strategy from a very large library of small molecule inhibitors. The relevant research results were published in the journal Nature Communications on January 25. This research marks another major progress in the transformation of regenerative medicine from basic research to clinical practice.

"The significance of this study is that it shows that we have been able to quickly develop a chemically defined medium to replace serum and trophoblasts for the cultivation of clinical-grade hES cells, thus clearing a major obstacle in the field of regenerative medicine, Said Chih-Ming Ho, a member of the National Academy of Engineering and a professor at the Henry Samueli School of Engineering and Applied Science at the University of California, Los Angeles.

Unlike the current animal product-based medium, this new medium is a defined medium, each of which is known and traceable. This is of great significance for clinical applications and for the good quality management and monitoring of drugs or cells.

"This is also the first known medium suitable for long-term single cell passage," said Professor Wu Hong, senior author of the paper. Wu Hong is a professor in the Department of Molecular and Medical Pharmacology at the David Geffen School of Medicine at the University of California, Los Angeles, and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research).

Single cell passage refers to the isolation and obtaining of single hES cells, and the subculture of single cell-derived clones. Single-cell passaging can overcome the large number of cell deaths associated with hES cell separation during conventional passaging and ensure genetic manipulation at the same cell level.

"Although there are other studies confirming that hES cells are cultured in a defined medium and / or on a defined culture surface, etc., to the best of our knowledge, this is the first combination of defined culture conditions with conventional single-cell passage. Research is of great significance for obtaining a large number of clinically applicable cells, "said Hideaki Tsutsui, the first author of the paper and a postdoctoral scholar at UCLA:" Our hES cell culture system has made hES cells an important step toward clinical treatment. "

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