Study: Two Molecules Speed Up Cell Reprogramming

Keisuke Kaji, PhD

Researchers in Scotland have identified 2 molecules that can speed up the production of cells for use in the lab. The finding could be a boon for researchers and drug makers working on therapies for conditions such as multiple sclerosis (MS).

The research holds the promise of solving what has been a frustrating problem.

“Reprogramming of cellular identity using exogenous expression of transcription factors (TFs) is a powerful and exciting tool for tissue engineering, disease modeling, and regenerative medicine,” the authors wrote. “However, generation of desired cell types using this approach is often plagued by inefficiency, slow conversion, and an inability to produce mature functional cells.”

In their new study, researchers at the University of Edinburgh write that 2 molecules (SMAD2 and SMAD3), both of which are naturally occurring in the body, can significantly speed up the process of cell production and boost the efficiency of the process.

Specifically, they found the molecules will aid in the generation of induced pluripotent stem cells (iPSC). These stem cells are produced from mature adult cells — such as skin cells — and can be programmed to become any type of cell.

Keisuke Kaji, PhD, a medical research council senior fellow at the university, told MD Magazine the researchers uncovered the molecules’ effect while looking into how the transcription growth factor-beta signaling pathway is related to cell reprogramming.

“While these molecules can be found in many cell types in the body, these molecules seem to help molecules which are uniquely existing in particular cell types, so-called cell type specific ‘master transcription factors’ and contribute to determining cell type-specific characters,” Kaji said.

The researchers also found that SMAD2 and SMAD3 can aid direct transformation of cells from adult skin cells to brain cells, effectively eliminating the iPSC phase. By doing so, the researchers cut the time it takes to generate brain cells in half, from about 50 days to just 25 days.

The research could be particularly important for MS, because one major line of current research is specifically looking at iPSCs and whether new brain cells can be generated to replace the cells charged with making myelin. Research into iPSCs is still relatively early, though other stem cell related research, specifically that focusing on mesenchymal stem cells, is being tested in phase 1 and 2 clinical trials.

In addition to facilitating better study of diseases like MS by boosting cell production in the lab, the research could also make it easier for drug companies to test therapies for toxicity and efficacy in a lab setting.

Notably, Kaji said the strategy his team discovered for speeding up cell reprogramming is not hard to implement.

“Yes, it is simple and easy to apply,” Kaji said.

Kaji believes SMAD2 and SMAD3 could also speed up production of other types of cells beyond the scope of their study.

“We hope other researchers try them in other contexts as well,” Kaji said.

The study, “Constitutively Active SMAD2/3 Are Broad-Scope Potentiators of Transcription-Factor-Mediated Cellular Reprogramming,” was published online last month in Cell Stem Cell.