INDUCED PLURIPOTENT STEM CELLS SHOW PROMISE
Imagine being able to reprogram one of your own skin cells to produce a functioning nerve cell or section of cardiac tissue. This may sound like science fiction — but the groundwork for this to become a reality is already in the works as researchers expand their ability to create and manipulate induced pluripotent stem cells.
In this WEEKLY, we’ll get the details on what these multifaceted cells are all about and discover their therapeutic potential.
STEM CELL PRIMER
Stem cells are unspecialized cells that have the ability to develop (differentiate) into 1 of 200 cell types in the body. There are two general classifications:
- Embryonic stem cells (found only in developing embryos) can become any cell type within the adult body. These are pluripotent stem cells.
- Adult stem cells (found in the organs of an adult) can only become certain cell types. Typically, these cell types come from the organ in which they are derived from.
Due to their ability to differentiate (change into) into any cell type in the adult body, pluripotent stem cells show the most promise as a therapeutic. The idea is they can be induced in the lab to form a specific type of adult tissue and then transplanted into a patient who needs that tissue.
For example, someone who damages their spinal cord may potentially benefit from a transplant of replacement spinal cord tissue. In fact, these types of clinical trials are currently ongoing and show promise. However, transplanting tissue derived from an embryo carries the same risks as an organ transplant — rejection by the immune system. Thus, patients undergoing this type of therapy must receive immunosuppressive drugs, which carries its own set of risks.
What could be a possible alternative that solves the rejection issue?
TERM OF THE WEEK: INDUCED PLURIPOTENT STEM CELL
An induced pluripotent stem cell (IPSC) is a type of pluripotent stem cell that can be generated directly from adult cells. In theory, this means that a scientist could create a stem cell treatment using cells from a patient’s own body by following these steps:
- Remove a skin or other easily accessible cell type from the patient.
- Manipulate the cell in the lab to produce an induced pluripotent stem cell.
- Add the required growth and differentiation factors to get the induced pluripotent stem cell to differentiate into the desired tissue type.
This newly differentiated tissue could then be transplanted back into the patient’s body without fear of immune rejection since it is derived from their own cells!
AN EASIER RECIPE
The development of IPSCs was so significant that the scientists at Cambridge University (Cambridge, UK) and Kyoto University (Kyoto, Japan) who figured out how to create them received the 2012 Nobel Prize in Medicine. Their discovery was based the observation that when pluripotent stem cells differentiate into specialized cell types, certain genes are deactivated or switched off. They wondered if the reverse might also be true — if by reactivating or turning on those same genes, they could arrive at pluripotency. Through a series of experiments, they hit upon the correct combination of genes to reactivate, and succeeded in inducing pluripotency.
The best way to decipher a disease is to examine the affected cells from a patient — for example, a blood sample from a leukemia patient or a tumor biopsy from a breast cancer patient. What if the affected tissue is impossible or dangerous to access — such as brain or cardiac tissue? IPSCs to the rescue! To better understand Alzheimer’s, researchers are creating IPSCs from Alzheimer’s patients’ skin cells, which are then induced to become brain cells. In this manner, the disease models reflect the genetics of an Alzheimer’s patient without the need to directly access their brain cells. These patient-based disease models are being used as both a way to better understand the disease process as well as for drug discovery research.
Companies developing IPSC-based drug discovery platforms include:
- Evotek’s (Hamburg, Germany) collaboration with Celgene (Summit, NJ) to use their IPSC platform to discover and develop new drugs for a range of neurodegenerative disorders, including Alzheimer’s, Parkinson’s, and ALS.
- Axiogenesis’ (Cologne, Germany) collaborations with Metrion Biosciences (Cambridge, UK) to develop IPSC-derived heart muscle cells and neurons for drug discovery applications.
Ultimately, scientists and physicians want to use patient-derived IPSCs for individualized treatments as described above. Currently, there is only one ongoing clinical trial using IPSCs, taking place at the RIKEN Institute (Wako, Japan) for the treatment of wet age-related macular degeneration. The scientific community is closely watching this trial — if IPSC treatments prove to be safe and effective, they will revolutionize an already revolutionary field.
Emily Burke, PhD has worked in biopharma for 20 years, gaining science writing experience at The Scripps Research Institute and Ionis Pharmaceuticals. As a Ph.D. molecular biologist, she is passionate about advancing the public’s understanding of science. In addition to being a self-proclaimed “science geek,” she is regularly asked to speak at international scientific meetings. When not teaching and writing the WEEKLY for Biotech Primer, Dr. Burke swims with her swim club and performs regularly on the improv circuit in San Diego.