Scientists from the La Jolla, California-based Sanford-Burnham Scientific research Institute recently discovered kinase inhibitors, that could help facilitate producing stem cells in the laboratory in addition to boost the amount of cells for projects related to disease research and drug development.
Researchers were initially thinking about quickening the procedure found in the production of induced pluripotent stem cells (iPSCs), a unique group of stem cells that can be based on any kind of an adult cell within the laboratory. iPSCs have been accustomed to produce cells of all types, including cells in the brain, heart and muscles.
The team of investigators found that kinase inhibitors could limit the activity of kinase, enzymes that really help in cellular communication, growth and survival. When they combined starter cells along with kinase inhibitors, they learned that they could produce more iPSCs compared to manner in which has been utilized previously by scientists.
“Generating iPSCs depends upon the regulation of communication networks within cells,” remarked the study´s senior author Tariq Rana, program director in Sanford-Burnham’s Children’s Health Research Center, in a prepared statement. “So, when you begin manipulating which genes are switched on or off in cells to create pluripotent stem cells, you may be activating a lot of kinases. Since many of those active kinases are likely inhibiting the conversion to iPSCs, it made sense to all of us that adding inhibitors might lower the barrier.”
The scientists focused on identifying kinase inhibitors with a group of over 240 chemical compounds that limited kinase. The compounds were each added to the cell and many of the kinase inhibitors generated more iPSCs than the untreated cells. They discovered that the more powerful inhibitors centered on kinases AurkA, P38, and PI3K. Team members from Rana´s laboratory collaborated with personnel from Stanford-Burnham´s bioinformatics, animal modeling, genomics and histology core facilities to verify the findings of the study.
“We discovered that manipulating the activity of these kinases can substantially increase cellular reprogramming efficiency,” continued Rana within the statement. “But what’s more, we’ve also provided new insights in to the molecular mechanism of reprogramming and revealed new functions of these kinases. We hope these findings will encourage further efforts to screen for small molecules that may prove useful in iPSC-based therapies.”
With this new finding, researchers will be able to create new treatments and examine human disease. For example, researchers may use stem cells in Alzheimer´s disease studies in reproducing malfunctioning cognitive abilities from a person. These cells can then be observed in therapeutic drug testing.
“The identification of small molecules that improve the efficiency of generating iPSCs is a vital step forward in being able to use these cells therapeutically. Tariq Rana’s exciting new work has uncovered a category of protein kinase inhibitors that override the standard barriers to efficient iPSC formation, which inhibitors should prove useful in generating iPSCs from new sources for experimental and eventually therapeutic purposes,” Tony Hunter, a professor within the Molecular and Cell Biology Laboratory at the Salk Institute for Biological Studies and director from the Salk Institute Cancer Center, and unaffiliated with the study, said in the statement.