iPS cells not quite ready for primetime?

Are we ready to start using iPS cells in patients in the near future? Say in just a couple years?

Are they ready for primetime?

I think the answer is clearly “no”.

I believe that iPS cells, a new type of stem cells, are one of the most exciting and important developments in biomedical sciences in decades, but they are still far from being ready for clinic use.

iPS cells, also known by their full name “induced pluripotent stem cells” (you can read more about them here for background and also here in almost 20 different languages as part of my educational outreach page on stem cells), are embryonic stem cell (ESC)-like cells made from other types of cells such as skin cells.

No embryo is needed. In addition, because iPS cells would be made from a patient’s own cells and then given back as a transplant to that same patient, it is possible (thought not certain) that no immunosuppressive drugs would be need. It would be what is called an autologous transplant. A truly patient-specific therapy.

These are some very cool cells!

Overall, I am so excited about iPS cells that a couple years ago I dug into my own pocket and I bought the domain name www.ipscell.com for my stem cell blog. Believe me, it wasn’t cheap.

However, even I as one of the greatest fans of iPS cells on the planet, I do not believe that iPS cells are some kind of miracle as some would proclaim.

Six years after their first production, indeed we know a great deal more about iPS cells, but there remain some critical challenges and roadblocks before iPS cells can be used for stem cell-based regenerative medicine therapies.

I discuss some of these key challenges, focusing on regulatory issues in particular, to getting iPS cells from the bench to the bedside in a new review here.

As much as I am excited, I am also cautious when we are talking about introducing iPS cells are cells derived from iPS cells into actual patients. I believe that we still do not know enough about these cells to start using them for therapies. The cells remain unpredictable. When I was a kid growing up there was a group of comedians on Saturday Night Live called the “not ready for prime time players” (see picture above). I loved them because they were so funny in such unpredictable ways. Unpredictability is great for comedians on TV, but not so much for cells to be infused into patients.

Arguably the most important question is safety. iPS cells have the ability to form both benign and malignant tumors so the question of safety is not trivial. I believe that the iPS cell field has not adequately addressed the safety question in clinically relevant settings. Not even close. Whether iPS cells or their derivatives would form tumors in patients remains unknown. It’s unpredictable at this point due to lack of data.

One idea being promoted now, including by iPS cell pioneer Shinya Yamanaka, is to start now to make iPS cell banks for clinical use designed to be compatible with large numbers of potential future patients. CIRM is also gearing up to have an iPS cell bank, however there seems to be a key difference. CIRM’s bank is intended for research use, while Yamanaka specifically has the goal for his bank to be used clinically.

This difference is critical.

I like and support the idea of iPS cell banks. However, I do not believe the field has advanced far to support clinical use of iPS cells in the near future.

I realize that clinical use may nonetheless be on the horizon just a few years out in certain countries such as Japan, but in my opinion iPS cells are “not ready for primetime”, meaning not ready for clinical use. Not yet.

I also realize that some people in the stem cell field are going to be mad at me for saying this, but I believe it is true. People don’t read this blog to get sugar-coated, politically correct statements, right?

Too many key questions remain, particularly as I said about iPS cell safety. Others in the field, such as CIRM President Alan Trounson, agree that safety remains a key concern that has not been adequately addressed. Trounson in fact went so far as to say that it would be “premature” to start clinical trials with iPS cells. I agree with him.

The risk is that patients will develop tumors, a potentially catastrophic outcome for the patients and as well a tremendous setback not only for iPS cells but also for the whole stem cell field. There is in fact huge risk here and to deny or downplay that as some are doing helps no one in the long run.

iPS cells are amazing, but we need to learn far more about their safety in clinically relevant settings. We must also further enhance their production methods before we should start down a clinical path such as a bank intended for clinical use.

Otherwise we may find ourselves years down the road having spent 10s of millions of dollars, left with a bank of iPS cells made with what we only then realize are clinically unacceptable methodologies or unacceptable safety profiles. Although such a bank may have great potential for research, I don’t see it being ready to be used clinically. If it is regardless used for treating patients, again there is great risk of harm there.

It’s important as we move forward with iPS cells to temper expectations, while not losing sight of big picture goals such as clinical use of iPS cells at some future data. It’s a tricky balancing act to be sure, but crucial. So I support iPS cell banking for research as CIRM is doing, but I don’t think it is time yet to bank iPS cells for clinical use. That’s just asking for trouble.