Nav: Home

Scientists turn skin cells into heart cells and brain cells using drugs

April 28, 2016

In a major breakthrough, scientists at the Gladstone Institutes transformed skin cells into heart cells and brain cells using a combination of chemicals. All previous work on cellular reprogramming required adding external genes to the cells, making this accomplishment an unprecedented feat. The research lays the groundwork for one day being able to regenerate lost or damaged cells with pharmaceutical drugs.

In two studies published in Science and Cell Stem Cell, the team of scientists, who were led by Gladstone senior investigator Sheng Ding, PhD, and are part of the Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, used chemical cocktails to gradually coax skin cells to change into organ-specific stem cell-like cells and, ultimately, into heart or brain cells. This discovery offers a more efficient and reliable method to reprogram cells and avoids medical concerns surrounding genetic engineering.

"This method brings us closer to being able to generate new cells at the site of injury in patients," said Ding, the senior author on both studies. "Our hope is to one day treat diseases like heart failure or Parkinson's disease with drugs that help the heart and brain regenerate damaged areas from their own existing tissue cells. This process is much closer to the natural regeneration that happens in animals like newts and salamanders, which has long fascinated us."

Chemically Repaired Hearts

Adult hearts have a very limited ability to generate new cells, so scientists have searched for a way to replace cells lost after a heart attack, such as transplanting adult heart cells or stem cells into the damaged heart. However, these efforts have been largely ineffective, as most transplanted adult cells do not survive or integrate properly into the heart, and few stem cells can be coaxed into becoming heart cells. An alternative approach pioneered by Deepak Srivastava, MD, director of cardiovascular and stem cell research at Gladstone, used genes to convert scar-forming cells in the heart of animals into new muscle that improved the function of the heart. A chemical reprogramming approach to do the same may offer an easier way to provide the cues that induce heart muscle to regenerate locally.

In the Science study, the researchers used a cocktail of nine chemicals to change human skin cells into beating heart cells. By trial and error, they found the best combination of chemicals to begin the process by changing the cells into a state resembling multi-potent stem cells, which can turn into many different types of cells in a particular organ. A second cocktail of chemicals and growth factors helped transition the cells to become heart muscle cells.

With this method, more than 97% of the cells began beating, a characteristic of fully developed, healthy heart cells. The cells also responded appropriately to hormones, and molecularly, they resembled heart muscle cells, not skin cells. What's more, when the cells were transplanted into a mouse heart early in the process, they developed into healthy-looking heart muscle cells within the organ.

"The ultimate goal in treating heart failure is a robust, reliable way for the heart to create new muscle cells," said Srivastava, co-senior author on the Science paper. "Reprogramming a patient's own cells could provide the safest and most efficient way to regenerate dying or diseased heart muscle."

Rejuvenating the Brain with Neural Stem Cells

In the second study, published in Cell Stem Cell, the scientists created neural stem cells from mouse skin cells using a similar approach.

The chemical cocktail again consisted of nine molecules, some of which overlapped with those used in the first study. Over ten days, the cocktail changed the identity of the cells, until all of the skin cell genes were turned off and the neural stem cell genes were gradually turned on. When transplanted into mice, the neural stem cells spontaneously developed into the three basic types of brain cells: neurons, oligodendrocytes, and astrocytes. The neural stem cells were also able to self-replicate, making them ideal for treating neurodegenerative diseases or brain injury.

"With their improved safety, these neural stem cells could one day be used for cell replacement therapy in neurodegenerative diseases like Parkinson's disease and Alzheimer's disease," said co-senior author Yadong Huang, MD, PhD, a senior investigator at Gladstone. "In the future, we could even imagine treating patients with a drug cocktail that acts on the brain or spinal cord, rejuvenating cells in the brain in real time."
-end-
Nan Cao and Mingliang Zhang, both postdoctoral scholars at Gladstone, were the first authors on the Science and Cell Stem Cell papers, respectively. Other Gladstone scientists on the studies include Yu Huang, Ian Spencer, Yu Zhang, Baoming Nie, Min Xie, Haixia Wang, Tianhua Ma, Tao Xu, Guilai Shi, Saiyong Zhu, Kai Liu, and Ke Li. Researchers from the University of California, San Francisco and Case Western Reserve University also took part in the research.

Gladstone Institutes

Related Stem Cells Articles:

A protein that stem cells require could be a target in killing breast cancer cells
Researchers have identified a protein that must be present in order for mammary stem cells to perform their normal functions.
Approaching a decades-old goal: Making blood stem cells from patients' own cells
Researchers at Boston Children's Hospital have, for the first time, generated blood-forming stem cells in the lab using pluripotent stem cells, which can make virtually every cell type in the body.
New research finds novel method for generating airway cells from stem cells
Researchers have developed a new approach for growing and studying cells they hope one day will lead to curing lung diseases such as cystic fibrosis through 'personalized medicine.'
Mature heart muscle cells created in the laboratory from stem cells
Generating mature and viable heart muscle cells from human or other animal stem cells has proven difficult for biologists.
Mutations in bone cells can drive leukemia in neighboring stem cells
DNA mutations in bone cells that support blood development can drive leukemia formation in nearby blood stem cells.
Scientists take aging cardiac stem cells out of semiretirement to improve stem cell therapy
With age, the chromosomes of our cardiac stem cells compress as they move into a state of safe, semiretirement.
Purest yet liver-like cells generated from induced pluripotent stem cells
A team of researchers from the Medical University of South Carolina and elsewhere has found a better way to purify liver cells made from induced pluripotent stem cells.
Stem cell scientists discover genetic switch to increase supply of stem cells from cord blood
International stem cell scientists, co-led in Canada by Dr. John Dick and in the Netherlands by Dr.
Stem cells from diabetic patients coaxed to become insulin-secreting cells
Signaling a potential new approach to treating diabetes, researchers at Washington University School of Medicine in St.

Related Stem Cells Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...