Cardiac Stem Cell Science on Thin Ice

Posted by CorDynamics on May 21st, 2014

Solid Data Needed to Strengthen Case

by Dr. Michael Gralinski

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Every day I scan a variety of news outlets for the latest developments in the biotech field. Recently, a piece published online in Forbes grabbed my attention.

The article, “Stem Cell Therapy To Fix The Heart: A House Of Cards About To Fall?” discussed a scientific paper (BMJ) which concluded that many of the most exciting developments in clinical cardiac stem cell research are not true. In addition,  the purported benefits to patients with cardiovascular disease are at best very modest and likely non-existent. The authors call into question the recent reports of high profile stem cell research, citing the recent withdrawals of ‘landmark’ publications in prestigious journals such as Circulation and The Lancet.

What took me by surprise was this concise, yet elegant dissection of cutting-edge research was published in Forbes – a business journal. The Forbes authors did a fantastic job of explaining the detailed methods and rigor of analysis in the original BMJ article. (Both are compelling reads.) It also underscored a conversation I had with a colleague at a recent scientific conference. He too was struggling with how to incorporate cardiac stem cells into their offering. He told me his business development team loved the idea so they invested in building this into their services. However, the clients are not jumping on board and asking for it. Why? They aren’t will to spend finite R&D resources on a safety study without solid, validated data.

In the same vein, I recently attended the 2014 Society of Toxicology-Midwest Regional Chapter meeting at a venue outside of Chicago. The theme of this years’ symposium was “The Use of Stem Cells in Toxicology Evaluation”.

Most of the speakers were associated with companies offering stem cell technology as a fee-for-service/product. A few academicians also detailed their research in the field. In the main, the presentations were interesting yet felt commercial in nature. Again, from a business development side, it is an exciting prospect. However, after a few talks detailing how beneficial and predictive this technology is, I asked a simple question.

“What are the pitfalls and potential downside of using stem cells for drug safety screening?”

The answer was frankly very disappointing and even described as ‘wishy-washy’ from the apologetic speaker I was addressing – a leader in the field.

Many of us believe this technology has some interesting characteristics and the potential to streamline drug safety screening. It is clear the regulators are also moving in this direction. However, those of us who have seen these ‘transformative technologies’ come with a vengeance and disappear with a whimper are still looking for answers to questions and solid scientific data to help guide our opinions and ultimately our research. Good science will always lead to good business.

 

4 Responses to “Cardiac Stem Cell Science on Thin Ice”

  1. May 21, 2014 at 5:19 pm, Frank N. Sell said:

    I concur with your opinion Dr Gralinkski. The up-selling of stem cells for toxicity testing, especially cardiovascular safety assessment, need to be balanced by and with objective testing. Thanks for sharing the Forbes article…on a very timely topic.

    Reply

  2. May 27, 2014 at 6:23 pm, Ken Gibson said:

    It must be emphasized that the Forbes article which Mike refers to addressed clinical trials using stem cells as a human therapy, not the use of stem cells in toxicology evaluation and drug safety testing. These are two separate uses of stem cells and should not be interpreted as the same science or application. Mike then addressed recent presentations at the 2014 SOT Midwest Regional Chapter. Unfortunately he “mixes” the various science presentations with a single question to a speaker.

    As an author and reviewer, I can assure my scientific colleagues there is substantial industrial and academic laboratory work ongoing to validate hiPSC cardiomyocytes as a safety pharmacology technology ( K Harris et al , J Ma et al . ). This process is also is clearly stated by the HESI CiPA program which Mike refers to in his last paragraph. However, this safety pharmacology work with hiPSC cardiomyocytes does not receive extensive financial support and extensive publicity from NSF, NIH, FDA, etc. These government agencies primarily support therapy to treat human disease. While one may identify safety pharmacology supported by the NIH or FDA, it is a very small percentage of government funding. Thus it is often “left” for large pharma companies and CROs to provide “science” on the benefits and predictive value of such new, disruptive technology. While the few CROs working on hiPSC will benefit to present/publish such data, large pharma companies seek to maintain such data in a confidential, non-disclosed state.

    In summary, difficulties with the use of hiPSC as a human therapy should not be confused with extensive ongoing efforts to streamline drug safety testing with hiPSC. Good science is being accumulated about the benefits of this technology to improve and reduce the costs of drug discovery and development. However, as Mike surely would agree, it will take time to accumulate and evaluate any “good science” which leads to better drug discovery and development.

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    • May 30, 2014 at 7:13 pm, Michael Gralinski said:

      Thanks for the comments Ken, you raise a number of good points.

      As stated in the original blog, the Forbes piece was from a clinical study using stem cells. I was using the clinical paradigm to set up a premise – that we should proceed into these nascent technologies with caution, not abandon.
      The organizations that are methodically examining the use of human stem cells in drug safety are few in number. Indeed, interrogations based on good science are being conducted and reported. However, increasingly numerous are the presentations from vendors with little to no prior experience in this or even related technologies.

      The low barrier to entry with in vitro models has the potential to flood the market with loosely conducted validation experiments, and frankly wholly inaccurate conclusions based on fundamentally flawed assumptions. We saw examples of this at the Chicago meeting referenced, as well as others prior. Most disconcerting is the acceptance of this data by audiences who are new to the field.

      I don’t want to see another repeat of how hERG/IKr antagonism studies were monetized as ‘gold standard’ predictors of some level of CV risk starting in the early 2000’s. Because of that Wild-West mentality data was being generated at a frenetic pace without regard to experimental conditions, preclinical/clinical translatability, nor suitability of the interpretation. Now we know that a more restrained approach to the problem would have been more appropriate. Let’s not repeat the last convoluted 15 years with human stem cells.

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