Curing Diseases and Regenerating Limbs with Skin

By Maria Tian, Geisinger Commonwealth School of Medicine, MBS 2023
Mentor: Dr. Gregory Shanower, Ph.D.
 
What if a missing eye could be replaced? Or a missing arm? What about curing Alzheimer’s disease, or reversing cancer? These are some of the ambitious solutions IPSC (induced pluripotent stem cell) therapy seeks to provide.
 
IPSC therapy generates stem cells from skin cells. These stem cells can be further transformed into any other cell in the body, such as those found in the heart and brain. To date, scientists have used IPSC therapy to create various tissues and organs; the use of starter cells has also expanded beyond the skin to cells such as hair. In one recent experiment, hair cells were used to successfully create beating sheets of heart tissue. Another experiment created sheets of muscle tissues from the skin. These methods provide less harm to the patient, unlike previous procedures, where stem cells were extracted from human fetuses. Compared to tissues created using foreign materials, there is also a higher likelihood that IPSC-created tissues will merge and survive in the patient since the tissue originally comes from the patient’s cells.
 
While IPSC therapy may sound cool so far, there are some current challenges we must address and overcome before the therapy can be used in humans.
 
One challenge is the presence of DNA mutations when skin cells are transformed into another type of cell, which creates a severe shortage of usable cells. Additionally, DNA mutations can lead to the development of many issues such as bad protein production or tumor formation.  
 
Currently, it is also very difficult to detect and separate the good cells from the bad. This inefficiency not only inflates research costs but also requires excessive amounts of the patient’s cells before a small batch of good cells can be used.
 
Another challenge is that the transformative process takes a long time, which can span weeks or even months. Sometimes, this long duration is not realistic since conditions like heart disease can quickly cause the death of a patient.
 
Lastly, new tissues can quickly die off after insertion back into the original organism. This observation is intriguing and shocking since the previous hypothesis believed that the tissue should successfully be accepted back into the body. A study found that cells quickly decreased in number within two weeks. One hypothesized cause is that the new environment cannot provide the original support of the cells and activates apoptosis or programmed cell death. Additionally, the mechanical stress exerted on the cells during insertion can also threaten cell survival. This issue should be further explored since this is an important step for IPSC therapy to become usable in humans.
 
A big portion of the current research involves using IPSC cells in labs to help scientists discover new drugs and therapy options. This is a big advancement in personalized medicine where a drug can be tested for safety in the patient’s cells before it is given to the patient.
IPSC cells are also transformed to mimic diseases which can help scientists better understand what the disease is like and how to treat them. In Parkinson’s disease, IPSC cells helped scientists find 17 genes that were causing the disease. Another hot area of research is studying how IPSC therapy can be used to treat diseases that may be fixed with new tissue replacements including neurodegenerative diseases, cardiovascular diseases, and wound repair.
 
As IPSC therapy currently stands, I believe it has tremendous promise to one day be viable for human use. Given its potential to provide a cure for many incurable diseases such as Alzheimer’s disease and cancer, I believe more funding and resources should be input into IPSC therapy research. While there has been great progress in successfully turning skin and hair into other types of cells, there are many barriers we must address. It is commendable that we are taking a big step in the right direction by recognizing the problem to direct our research. In general, I believe research in stem cells is headed in the right direction by identifying more convenient, ethical, and safer methods to cure major health conditions and diseases. It is with optimism that I hope for a world where one day a heart attack can be a thing of the past and loved ones are not forgotten.