Through their lens: Heather Macomber investigated the possibility of immune rejection of iPS and embryonic stem cells

This summer we’re sponsoring high school interns in stem cell labs throughout California. We asked those students to contribute to our Instagram photos and YouTube videos about life in the lab, and write about their experiences.

Heather Macomber worked in the lab of Jeanne Loring at Scripps Research Institute.

Heather Macomber working in the lab. She submitted this photo through Instagram to CIRM’s #CIRMStemCellLab collection.

This summer CIRM has given me an astonishing opportunity to study the immunology of induced pluripotent stem cells (iPSCs). These cells have the potential to create more accurate and patient specific drug screening, and replace damaged cells and organs within the body without the risk of immune rejection. To study this exciting possibility, under the mentorship of Victoria Glenn I’m working to investigate the expression of the Major Histocompatibility Complex, MHC, within two stem cell lines. MHC is a molecule of the human immune system; it is used in hospitals as the main indicator if a donor organ will be rejected by a patient’s immune system. Because iPSCs are a relatively new cell type, we decided to investigate the levels of expression of MHC. There has been some argument that differentiated human pluripotent stem cells do not express any MHC. If this were true, doctors wouldn’t need to worry about matching immune systems from donor iPSCs to patients. My mentor’s previous work has provided evidence contrary to this notion. It has shown that when stem cells are in their undifferentiated, pluripotent state they do not express MHC, but when they are differentiated towards a linage expression does rise. She specifically tested cardiac and neural progenitors. These data indicate that immune profiles do need to be considered when looking at induced pluripotent stem cells for transplant.

To continue this research, I differentiated two lines of human pluripotent stem cells, the h9 (embryonic stem cells) line and an internally created induced pluripotent stem cell line, into cardiac progenitor cells. We decided to stop differentiation at this stage because it is most promising for clinical application. When implanted into mouse models, multipotent progenitors are more successful then either undifferentiated or fully differentiated cells at repairing damaged tissue. For reasons still unknown, the multipotent progenitors appear to be in the “goldilocks” zone for regenerative ability. To understand the gene expression of cells from both E9 and iPSC lines, I will analyze them using real time PCR and immunocytochemistry. By using ICC, I expect to prove that these cells have properly differentiated into the cardiac progenitors we’re looking for. Additionally, by comparing an E9 line to an iPSC line, I hope to add to a body of evidence that shows these cell types to be clinically indistinguishable. Through PCR, I will investigate the expression levels of MHC as well as confirming the cardiac progenitor state of my cells. This step will help us evaluate the expression of proteins, which are known to interact with the immune system. These data will be used in further research to investigate various other immune system responses.

CIRM and the Loring lab have provided me with an opportunity that has taught me indefinite amounts of information in a short time. By being immersed in a lab culture, I have quickly learned a variety of terms and soaked up knowledge about stem cells, so that I can converse fluently with fellow researchers. By carrying out real world experiments on the frontier of modern science with highly relevant impacts, I have been further inspired to become a research scientist. In addition, my exposure to stem cell research and induced pluripotent stem cells in particular has peaked my interest in this emerging and exciting field. I hope to further explore this field as I move forward in my scientific and creative endeavors.

Heather Macomber

Heather submitted this video of her experience:

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