The possibilities are tantalizingly close, and almost--but not quite--within our grasp.
Like human embryotic stem cells, human-induced pluripotent stem cells (HiPSCs) have the ability to differentiate into more than 200 specialized human cells. Learning to use this remarkable potential in patient care could be the key to treating and curing a broad spectrum of diseases and disorders.
Although the science of stem cells has advanced rapidly in recent years, it is difficult to re-program quality cells fast enough to provide an adequate supply for treatment.
Now, a reprogramming factor identified by a UAB Stem Cell Institute team led by Kejin Hu, PhD, in the Department of Microbiology and Molecular genetics, has increased the efficiency of reprogramming skin fibroblasts into HiPCS by more than 20-fold. In addition to speeding the reprogramming process by several days, it also enhances the quality of the reprogrammed cells.
“The factor we used to accelerate reprogramming is a kinase protein known as BRD3R that reads acetylated histone codes in the chromosome,” Hu said. “We used xeno-free media, without mouse feeder cells or serum from any sources. In the future, xeno-free production will be an FDA good manufacturing practice requirement for clinical use of human iPSCs.
“Another issue that has been a concern in the past is the possibility of introducing tumorigenic cells into patients. One of the goals of our research has been to establish protocols to eliminate these cells from HiPSC-based transplants,” Hu said. “Our lab found that by targeting the marker surface protein PODXL using a well-established antibody, we can kill tumorigenic pluripotent cells.”
Being able to re-program high quality stem cells faster should make supplies more available for research into how diseases develop and evolve, and in the development of drugs to treat them. It will also open the door to broader research in regenerative medicine, cell therapy, gene therapy and tissue engineering.
HiPCS are already being tested in clinical trials to treat macular degeneration and inject retina cells to reverse blindness. They offer exciting possibilities for at last developing treatments for spinal cord injuries and neurodegenerative disorders including Parkinson’s Disease, Huntington’s Disease and ALS. Regenerating damaged heart tissue in cardiomyopathy and undoing the damaging effects of diabetes are more examples of how stem cell therapies could soon revolutionize the practice of medicine.
“Another major advantage in re-programming is the ability to transplant cells from the patient’s own body, which eliminates the risk of an immune system reaction to donor cells,” Hu said.
Funded by the UAB Faculty Development Fund and The Alabama Institute of Medicine, the research that identified the reprogramming factor was conducted by Hu and members of his team, Chunping Yao, MD, Weihua Xu, PHD, Alireza Khodadadi-Jamayran and Ruowen Zhang, PHD.
Increasing re-programming efficiency to more cells available faster has taken stem cell research one step nearer the day it will offer routine therapies for disorders that are now difficult or impossible to treat. However, there are still many questions that need to be answered.
“The next challenge science will have to solve is differentiation. Labs around the world are working on this. HiPSC cells can become any type of cell. We need to find better ways to direct them to become the type of cells we need,” Hu said.
Judging by the pace that stem cell science has advanced in the past ten years, approved therapies using this exciting new tool may not be so far away. But how far are we from the dream of one day growing differentiated stem cells into organs for transplant?
“That could be a while. There would be many, many questions to solve,” Hu said. “We may not be able to grow organs very soon, but organoids, yes. We are already growing tissue on a matrix. The science has come so far, so quickly.”
