In this segment, Chad Cowan explains why effective drugs for heart attack and diabetes are lacking: the underlying disease mechanisms, driven by many small‑effect risk alleles, are poorly understood. Traditional viral reprogramming methods integrate into the genome, making it hard to separate the genetic contribution of disease from artifacts introduced by the reprogramming factors. Cowan highlights the advantage of Life Technologies’ Sendai virus reprogramming kit, a non‑integrating RNA virus that leaves no residual reprogramming factors after 5–8 passages, yielding iPSC lines with an unblemished genome. These genome‑intact iPSCs can be derived from patients with cardiovascular disease or diabetes, then differentiated into any desired human cell type—such as adipocytes—to directly assess disease‑related phenotypes like insulin resistance. This approach provides a powerful platform to dissect the genetics of complex metabolic diseases and accelerate drug discovery.
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You can ask yourself, like, why aren't there better drugs available for heart attack or for diabetes? And it's because We don't know enough about the disease mechanisms. We don't know how the diseases are caused. In my own lab, we wanted to understand metabolic disease, so diabetes and cardiovascular disease. These diseases aren't similar to a lot of the rare monogenic disorders that get really profound phenotypes. Often these diseases have small risk alleles that all of us carry around that put us at risk for developing the disease, you know, 20, 30, 40 years later. And studying these very small effects is difficult to do in stem cells, especially stem cells that have been reprogrammed by sort of the traditional techniques. I think it's immediately apparent to any scientist who wants to study the genetics effect of the disease that if you alter the genetics of the cell type that you're working with by integrating viruses, you're going to have enormous amount of difficulty teasing out what is the backbone genetic contribution versus the altered cell type contribution. So by being able to create cells that are intact and have no modifications to the genome, you can really feel secure that what you're looking at now is the genetic contribution to the disease. We were, of course, thrilled to see that Life Technologies had made available a new product, the Sendai virus reprogramming product, which is as simple as the lentiviral reprogramming or the retroviral reprogramming, but has this major advantage that there are no reprogramming factors left. It's fully non-integrating. It takes— makes use of this RNA virus, the Sendai virus, that's non-replicative, that you infect the cells just one time. Usually within 18 to 21 days, we see the appearance of iPS cell colonies. After we've expanded those colonies and actually established a line, by the time they've been passaged 5 to up to 8 times, there's no presence of this RNA virus anymore. So the lines, in essence, have an unblemished genome and they have none of the reprogramming factors left. So you've really got the best possible material for doing the types of studies we're interested in. [MUSIC] So what we have now is a unique opportunity. One of the best studied groups of people with the types of disease we care about, heart attacks in their history or elevated cholesterol. And we have the opportunity to draw blood from these patients and try to create iPS cells to try to understand this relationship. What would really unlock the mystery of this interesting disease biology is the ability to again and again make any human cell type that you might imagine from almost any human on the planet. So if you could say anybody with this type of diabetes, I want to make a fat cell out of and find out if there's insulin resistance, We now have the opportunity to do that. That's what induced pluripotent stem cell technology gives us the key to.
