Simple Trick to Grow Stem Cells From Mature Cells Discovered, Important for Therapies

The current difficulty of growing large batches of stems cells from mature cells in patients to be used in advanced therapies could be solved in a quite simple way by blocking a single protein, researchers say.

Scientists hope lab-grown stem cells and induced pluripotent stem (iPS) cells, which have the ability to produce specialized cells such as neurons and cardiac cells, could one day be used to treat diseases and repair damaged tissues.

“Even though stem cells are able to self-renew, they are quite challenging to grow in the lab,” says co-author Jeffrey S. Isenberg, associate professor at the University of Pittsburgh. “Often you have to use feeder cells or introduce viral vectors to artificially create the conditions needed for these cells to survive and thrive.”

In 2008 Isenberg worked in the National Cancer Institute (NCI) lab of senior author David D. Roberts, using agents that block a membrane protein called CD47 to explore their effects on blood vessels. He noticed that when cells from the lining of the lungs, called endothelium, had been treated with a CD47 blocker, they stayed healthy and maintained their growth and function for months.

Roberts’ current National Institute of Health (NIH) team continued to experiment with CD47 blockade, focusing on defining the underlying molecular mechanisms that control cell growth.

They found that endothelial cells obtained from mice lacking CD47 multiplied readily and thrived in a culture dish, unlike those from control mice. Lead author Sukhbir Kaur, discovered that this resulted from increased expression of four genes that are regarded to be essential for formation of iPS cells.

When placed into a defined growth medium, cells lacking CD47 spontaneously formed clusters characteristic of iPS cells. By then introducing various growth factors into the culture medium, these cells could be directed to become cells of other tissue types. Despite their vigorous growth, they didn’t form tumors when injected into mice, a major disadvantage when using existing iPS cells.

“Stem cells prepared by this new procedure should be much safer to use in patients,” Roberts notes. “Also, the technique opens up opportunities to treat various illnesses by injecting a drug that stimulates patients to make more of their own stem cells.”

According to Isenberg, “These experiments indicate that we can take a primary human or other mammalian cell, even a mature adult cell, and by targeting CD47 turn on its pluripotent capability. We can get brain cells, liver cells, muscle cells, and more. In the short term, they could be a boon for a variety of research questions in the lab.”

In the future, blocking CD47 might make it possible to generate large numbers of healthy cells for therapies, such as alternatives to conventional bone marrow transplantation and complex tissue and organ bioengineering, he added.