During the past year, we have used the funds from this grant to derive a new embryonic stem cell line with an inherited mutation that results in a severe cardiovascular and bone disease called Marfan syndrome that affects more than 7,500 Californians. In addition, using adult skin cell lines with the same inherited disease, we have made significant progress deriving iPS cells with Marfan syndrome. During the next year we also hope to expand our studies by recruiting patients with a disease very similar to Marfan syndrome called Loeys-Dietz syndrome, to donate skin biopsies so that we can make iPS cells to study that disease as well. Using these new stem cell lines, we are testing whether the iPS and embryonic stem cells are truly functionally the same, by comparing them after we make them become cardiovascular and bone cells.
One of the biggest challenges in stem cell biology is figuring out how to make the stem cells become the adult cells we want to study and not some other random adult cells. Over the past year, we have made great strides in turning our stem cells into the cell types most severely affected in people with Marfan syndrome, namely bone and cardiovascular cells. What is most exciting to us is that even with these preliminary studies, it looks like we might be seeing differences between the stem cells with Marfan syndrome and normal stem cells after they are coaxed into become the bone and cardiovascular cells. These results are still very preliminary though, and we need to take great care during the next year to rigorously repeat our experiments before we can be certain of those results. If we can reproduce the differences, these differences may be the basis for screening for new drugs to treat people with Marfan syndrome or lead to a better understanding as to what exactly is the sequence of cellular events that leads to the patient’s symptoms. What’s more, by studying how to efficiently make bone and cardiovascular cells from human embryonic stem cells and iPS cells in the dish, we hope to provide important data that could be beneficial in a wide variety of applications such as tissue engineering or cellular replacement therapies using bone or blood vessels.