Aren't iPS cells the future?

Posted by Benjamin Buller on

When talking to friends, colleagues, and others about Forever Labs, those among them with a certain level of knowledge in the biosciences often turn the conversation to iPS cells. Specifically, they want to know why we're trying to do what it is we're trying to do when iPS cells will dominate the market sooner rather than later. So, what is an iPS cell, exactly? iPS stands for "induced pluripotent stem" cell. It's a method of turning normal, everyday adult cells into cells that behave like those that exist very early in development. Basically, researchers have found a way to make a skin cell (for example) turn into any other cell type by reverting its phenotype (basically, the "flavor" of the cell) to one that resembles a cell of a very early stage embryo. An embryonic cell is in some way magic: it can become any adult cell type in the right condition. This work is so revolutionary that its discoverer, Shinya Yamanaka, was awarded the Nobel Prize a mere six years after the technique was introduced. In Nobel years, that's the equivalent of a split second.

iPS cells have an undeniable future in medicine. In theory one can regrow any organ or tissue if the recipe is right. In fact, clinical trials are slated to begin shortly based on the success of a small pilot study that used these cells to treat a specific eye ailment in elderly people (age-related macular degeneration). But iPS cells are not a panacea, and some very troubling facts may stunt their wider adoption. First, iPS cells have the ability to form tumors, and do so readily when injected into mice. To overcome this in the clinic, they must be differentiated in culture to a cell that looks more like a "terminally differentiated" cell (the cell the doctors want it to become once in the body). Macular degeneration was chosen for two specific reasons. The cells that are to be recovered are brown in color, due to a pigment they express, which makes them easy to identify, but relatively unique among all cells in the body, which are normally very difficult to distinguish using only a light microscope. And, one can easily look through the pupil to the retina to directly observe whether a tumor is forming. These are unique to this disease, and may not be widely applicable to the majority of human pathological conditions.

Second and I think more importantly, the cells themselves are not young. It's fair to ask the question of whether a cell "knows" its age, because on the surface it seems like a ridiculous thought. But nature has provided us with many examples of preprogrammed age that supersedes what we may think logic dictates. Take for example the starfish. Certain species are known to not only regenerate severed limbs, but the lone limbs themselves can, if enough tissue is intact, grow an entirely new starfish. This is remarkable, but a truly more remarkable thing is that even though the starfish is made of almost entirely new flesh, its lifespan is no longer than the original organism from which it was detached. Think about that for a minute. This is the exact opposite of the Dr. Who effect, where regeneration begets a new lifespan. So, why might this be? My speculative answer is that the cellular DNA, which is unchanged in iPS cells, is fraught with damage. DNA tends to get shorter over time, and this shortening correlates to lifespan. Furthermore, cells accumulate "stuff" as they age, modifications to DNA, proteins, RNAs, etc, that all contribute to its character and its age. Evidence suggests that bone marrow stem cells also accumulate baggage as they age, making young cells qualitatively different from older ones. So far, to my knowledge, the iPS community has been unable to address the contextual life of the cell. There has been some recent work on cellular age in reprogrammed cells that I will cover at some point in the future, but I think the work (even though it mostly supports my point) is too nascent to comment on with any authority.

It's entirely possible that these problems will be overcome, but it won't be soon and it won't be inexpensive. A treatment course in the aforementioned macular degeneration study costs upwards of $200,000. Even if that comes down by half or more we're still contemplating some serious money. When you factor cost with tumor risk and cellular age, the hurdles that iPS cells need to overcome may relegate them to niche treatments for the foreseeable future. There is a future in iPS, but not as the catch all that many proponents envision.

← Older Post Newer Post →