Researchers in the laboratory of cardiologist Joseph Wu, MD, PhD, are working to clear up an essential stem cell mystery — how closely do cells made from induced pluripotent stem cells mimic the function and gene expression of the native tissue? In other words, do lab-grown heart muscle cells twitching in a cell culture dish mirror those beating in that person’s own heart? The answer, which was published in Cell Stem Cell this morning, has important implications for nearly all aspects of regenerative medicine.
From our release:
The ability to create stem cells from easily obtained skin or blood samples has revolutionized the concept of personalized medicine and made it possible to create many types of human tissue for use in the clinic. Researchers have wondered, however, whether the process of creating stem cells, and subsequently coaxing those stem cells to become other tissues, might affect the patterns of gene expression and even the ways the specialized cells function. If so, these changes could limit their clinical usefulness.
The researchers, led by cardiovascular medicine instructor Elena Matsa, PhD, created several batches of iPS cells from seven people not known to be predisposed to cardiac problems. They then coaxed the cells to become beating heart muscle cells called cardiomyocytes, and compared the patterns of gene expression both within and among the individuals.
As Matsa described:
We found that the gene expression patterns of the iPS cell-derived cardiomyocytes from each individual patient correlated very well. But there was marked variability among the seven people, particularly in genes involved in metabolism and stress responses. In fact, one of our subjects exhibited a very abnormal expression of genes in a key metabolic pathway.
Furthermore, the cells from the individuals responded in varied ways to increasing amounts of two drugs associated with adverse cardiac effects in some people, validating a key potential use of iPS-derived tissues — predicting how a patient might react to a particular drug.
As Wu, who directs the Stanford Cardiovascular Institute, explained:
Many people talk about precision medicine or precision health, but there are only few examples of how to carry it out in a clinically meaningful way. I think the patient-derived iPS cell platform gives us a surrogate window into the body and allows us to not only predict the body’s function but also to learn more about key disease-associated pathways.
Previously: Predicting chemo-induced heart damage using iPS cells, A cheaper, faster way to find genetic defects in heart patients and Stem cell study explains how mutation common in Asians affects heart health
Image of heart cells courtesy of California Institute for Regenerative Medicine