Very soon, patients suffering brain or spinal cord injury or a heart attack could be treated using a drug cocktail that kickstarts new cell formation at the site of injury. By using a combination of nice chemicals, researchers at Gladstone Institutes have transformed skin cells into functioning heart and brain cells in a pionerring first.
The team first changed the skin cells into multipotent stem cells that can potentially develop into various cell types. They then converted these into organ specific heart and brain cells. In the first study led by first author Nan Cao, PhD, a postdoctoral fellow, more than 97 percent of the cells were converted into healthy, beating heart cells that resembled heart muscle cells. When transplanted into a mouse heart, they developed into healthy heart muscle cells in the heart.
In the second study authored by Gladstone postdoctoral scholar Mingliang Zhang, all the skin cells were transformed into neural stem cells which when transplanted into mice became neurons, oligodendrocytes, and astrocytes -- three basic types of brain cells. They were able to self-replicate, proving the method ideal for treating both neurodegenerative diseases and brain injury.
"This method brings us closer to being able to generate new cells at the site of injury in patients," said Sheng 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."
Cells lost during a heart attack in adults have been replaced by transplanted heart cells or stem cells, but the technique has low success rate due to rejection and difficulty in coaxing stem cells to become heart cells. The approach pioneered earlier on by Deepak Srivastava, MD, director of cardiovascular and stem cell research at Gladstone, used genes to convert scar-forming cells in the heart into new heart muscle cells. The latest chemical reprogramming approach could lead to an easier way to induce heart muscle to regenerate locally.
"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."
Stem cells are the body's growth and maintenance units that are able to differentiate indefinitely into specialised cell types, first in the growing embryo into various organ cell types, and later form the body's repair mechanism by producing new cells when the tissue they reside in is damaged.
The most useful stem cells are those derived from embryos known as "pluripotent" stem cells as they can differentiate into any cell type in the body. Adult stem cells also can develop into many cell types but they are not as flexible as embryonic stem cells.
In the lab, the problem has been to grow sufficient numbers of stem cells and to coax them to divide under lab conditions. The growth factors to simulate growth have been difficult to pin down and often the cells lose their viability after transplantation.