Induced Pluripotent Stem Cells

What if an ordinary skin cell could forget its identity, transform back to its earliest state, and re-develop into almost any kind of cell it needed to be – such as a heart, brain or retina cell – to repair damage from a myriad of diseases? Scientists are using induced pluripotent stem cells (iPSCs) to make the reversal of cell-fate possible. 

In 2014, a 70-year-old woman nearing blindness became the first person to receive a transplant of cells generated from induced pluripotent stem cells, or iPSCs.¹ They were grown from her own skin cells, which were genetically “rewound” to immaturity and coaxed into differentiating (or redirecting their development) into adult retinal cells instead. This next frontier of cell therapy holds the promise of turning iPSCs into almost any type of cell, and theoretically, any tissue type, to reverse the symptoms of many devastating medical conditions.

The Self-Renewing Signature of Stem Cells
As our body’s chief backup system, stem cells have a distinct ability to self-renew and give rise to various types of differentiated cells depending on their potency. In 2006, Dr. Shinya Yamanaka pioneered the development of “induced” pluripotent cells, or iPSCs. They can be cleared of the molecular tags that determine their original purpose (and were thought to be unchangeable), allowing them to mature into the cells of theoretically any organ.² This breakthrough opened new doors to regenerative medicine by offering researchers a virtually unlimited supply of stem cells created from reprogramming skin, blood or other donor cells. 

Compatibility is Key
There are different approaches to making iPSCs, but the end-goal is the same: replacing lost or damaged cells with exquisite compatibility with the patient. The autologous approach – generating iPSCs from a patient’s own stem cells – sidesteps the risk of immune rejection from donor cells, but is a longer and more resource-intensive process. The allogeneic approach derives mass-produced iPSCs from healthy donor cells to deliver “off-the-shelf” treatments; however, these cells can generate an immune response when transplanted. Experts predict that both methods will coexist in the future, and as the key to personalized medicine, selecting the right approach for the right patient is paramount.³

To produce an iPSC, skin or blood cells are retrieved via biopsy and transferred to a cell-culture dish where a special gene mix activates segments that were previously blocked off, providing open-access to the entire genome. Next, the iPSCs are exposed to specific growth factors to determine exactly which type of cell they will become before they can be used to study diseases or transplanted into a patient. This revolutionary method of stem-cell production holds great potential in disease research and regenerative medicine.⁴

Future Applications 
There is much research still to be conducted, but the exciting possibilities of iPSC-based therapy are numerous. The most viable disease targets are those which are caused by the failure of one type of cell.⁵ For example, iPSC-based approaches could potentially replace the dopaminergic neurons that degenerate in Parkinson’s disease; restore the dying photoreceptor cells in macular degeneration; and repair the dysfunctional insulin-secreting cells that cause diabetes.^4,6 One day, they could also help scientists model or artificially reconstruct entire organs, making it possible to simulate diseases and gain information at an earlier stage about the possible side effects of active investigational treatments.⁴ 

At Bayer, we believe in the potential of cutting-edge cell therapy such as iPSCs to revolutionize the future of personalized and regenerative medicine. Bayer and BlueRock Therapeutics are currently advancing a clinical study exploring the potential of pluripotent stem cell-based therapy to treat Parkinson’s disease, one of the most common neurodegenerative disorders in the world.

References:
_{¹Cyranoski, D. Japanese woman is first recipient of next-generation stem cells. Nature (2014). Accessed March 9, 2022.
²Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell (2006). Aug 25;126(4):663-76. Accessed March 9, 2022.
³Nature Research Custom Media and Bayer AG. New cells for old: The emerging potential of pluripotent stem cells in regenerative medicine. September 2021. Accessed March 9, 2022.
⁴Bayer AG. Cell and gene therapy: The next milestone in fighting diseases. Infographic: Producing and using pluripotent stem cells. Accessed March 9, 2022.
⁵Wallace Ravven. The Stem-Cell Revolution Is Coming — Slowly. The New York Times. January 16, 2017. 
⁶Si Z, Wang X. Stem Cell Therapies in AD. Journal of Pharmacology and Experimental Therapeutics May 1, 2021, 377 (2) 207-217. Accessed March 9, 2022.}