Researchers at Stanford have confirmed that specialised cells, grown from induced pluripotent stem cells, do in fact display gene expression mirroring the same cell type in the individual they were sourced from
In 2006 Shinya Yamanaka's lab discovered that cells could be reprogrammed back to a pluripotent state, in which they behaved in a similar way to embryonic stem cells. This brought new hope to regenerative medicine, but there have been doubts about cells formed from these IPSC cells.
Adult cells are taken from an individual and coaxed to become IPSCs, before being again instructed to differentiate into different cell types, for example cardiomyocytes or neurons. While this is an incredible process, many scientists questioned whether these final cells actually resemble the gene expression they should. Are these new cells acting in a similar way to the person they were originally taken from? If not, that would put a spanner in the works when it comes to precision medicine and drug development - using personalised, lab grown tissue to test drug responses and more.
"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"
To test whether these newly formed cells were activating the 'correct' gene expression, a team created pools of cells from 7 different people, and formed cardiomyocyte cells from each of these populations. They then scanned these cells for gene expression patterns to compare them to their original host, and added 2 heart drugs known to cause adverse health effects in some people. The researchers discovered that thankfully gene expression from iPS cell derived cells correlated with each individual correctly, and also gave a unique insight into unusual behaviour too.
"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. Patient-derived iPS cell platform give us a surrogate window into the body and allow us to not only predict the body’s function but also to learn more about key disease-associated pathways"
Read more at stanford.edu