Conversation with Brock Reeve, Executive Director of the Harvard Stem Cell Institute

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Conversation with Brock Reeve, Executive Director of the Harvard Stem Cell Institute

Lisa Girard


StemBook is launching its Forum feature with a series of interviews with a diverse group of prominent opinion leaders in stem cell research. Our first, Brock Reeve, is the Executive Director of the Harvard Stem Cell Institute (HSCI) in Cambridge Massachusetts. Along with the Faculty Directors, Brock , has overall responsibility for the operations and strategy of the HSCI whose mission is to use stem cells, both as tools and as therapies, to understand and treat injury and disease. A graduate of Yale and the Harvard Business School, Brock was in the commercial sector prior to HSCI, with an extensive background in management consulting and operations for technology-based companies, with a specialization in life sciences.

Below is an edited version of Brock’s conversation with StemBook’s editor, Lisa Girard


Can you tell StemBook reader’s about your role at HSCI as well as beyond, in the stem cell community?

 Sure, as you know the Institute was set up at Harvard as a way of helping to bring scientists, researchers and clinicians together across Harvard and its affiliated hospitals to engage in scientific research projects. We fund that work through private philanthropy so a large part of my role is helping to raise money to do the science and then working with our Executive Committee to decide where to invest our money.  We put our funds to work through the disease programs, seed grants, and core facilities that we build and manage, as well as in helping build the community of our researchers which now I'm happy to say has grown to about 95 Principal Faculty and about 170 Affiliated Faculty.


What are some of the greatest misconceptions still lingering about stem cell science in general population?

In the general population I think that people are still thinking about stem cell science as consisting of: a; embryonic stem cells, and b; stem cell therapy, i.e., cells as replacement parts, and are somewhat unaware of the additional potential that stem cells offer as tools and targets. As you know we are doing a lot of work  using stem cells to build in vitro disease models which help screen for drugs, whether more effective drugs or safer drugs.  We’re also working on understanding tissue specific progenitor cell populations so that we can learn how to enhance the body's innate ability to repair and regenerate. So I think it is on the tools and target side that people don't yet have an inherent appreciation, but I think with the advent of more research papers as well as some of the newer start up companies coming out of the labs that perception will start to change.


As you know, government funding for research in general is cut and the NIH funding is at low levels. Above and beyond that what do you feel are some of the biggest challenges facing stem cell researchers right now and do you think they face unique challenges keeping their labs funded?

 I don't think there are unique challenges.  I think that used to be true but as you mentioned, we are experiencing general economic pressures on government funding. NIH budgets have been flat for the last half-dozen years which means they have been declining in real terms which means there is lots of economic pressure on everyone in early stage research. We raise money from private philanthropy and then leverage that money with additional funding in terms of sponsored research from disease foundations and companies.   But the bulk of early stage, academic research is supported by federal funds and there is no way that private philanthropy is sufficient to fill the major funding declines.

 However, the good news is that private philanthropy has held up over the years.  Since HSCI was founded and as the economy has gone up and down and as Presidents have issued executive orders about the use of embryonic stem cells, our level of funding from private sources has been relatively constant and steady. What could affect this however, is the overall economic situation, which now looks better than it did a year or two ago but is still pretty shaky, and individuals’ wherewithal to give is dependent on the success of the overall economy.

 Another source of funding for us is sponsored research from foundations and companies. Due to capital market pressures and drug pipeline issues,  the bio-pharma companies have become more risk-averse and more focused on late-stage assets they can bring into their pipeline. But at the same time, several of them have started different forms and organizational structures to interact with academia because they know they need access to new ideas and  early-stage research.  Different companies are doing that in different ways so one question is how to interact in early-stage research with companies. We’ve had a multi-year partnership with GSK, for example, in several disease areas and it’s all  focused on stem cells to find more effective medicines.  We’re seeing interest from other pharmaceutical companies, none quite so broad as the GSK relationship in our case. I think as companies are looking to better connect with the basic research in academia which they know that they need and know they can’t do themselves, that they’ll reach out to the stem cell research community to help them do that.  Again, I don't think it's at a scale, amount or timeframe that'll, for example, supplant or backfill, for fewer funds from the NIH.  Also, corporations and foundations also tend to be more project specific and more focused in their funding. At the same time its also true that the NIH is emphasizing translational research,  It is always good, you know, to bring work out of the lab and into the clinic and the market, but we still have to worry about how basic questions get tackled and how we understand some of the basic biology before we can put it to work in people.


There are a number of stem cell-based start up companies. Can you talk a little about how this space, along with stem cell business models are evolving and what kind of progress is happening in this area?

I think there is there some progress. Some of your readers may have seen an article that I did with Chris Mason and colleagues in Cell Stem Cell on public cell therapy companies, and there are many companies in the cell therapy, regenerative medicine space, but those are only public companies. Many of them are focused on MSC type based therapies or cartilage, bone repair, skin, etc. So I think that you see an initial wave of companies there. I think the next wave of companies we're going to see, and these are companies that are not yet public, are going to be companies looking at not just cell therapy in and of itself but doing a couple things. One is, as I mentioned before, looking for drugs or biologics that can stimulate endogenous cell populations and I’d put those in the regenerative medicine/cell therapy bucket as well. Also, small molecule or large molecule companies where they have used stem cells as better models of disease.

A second area where I think there will be more work is in the engineering of cells. So we know that, for example, MSCs can home to a site of inflammation or injury and, by the way, as a footnote, several years ago claims regarding MSC trials were largely about MSCs differentiating into the cell lineages, which  we now know is not the case.  But we do know that in some cases they have clinical benefit and have been shown to be quite safe.  So the idea here is, can you use MSCs, or another cell type, as a delivery vehicle.  Consequently, we’re seeing work on the bioengineering front in terms of either manipulating cells on the outside to enhance their homing capability and/or using materials to get drugs into cells and using that cell as a delivery vehicle. So not the cell as therapy, but really the cell as, if you will, a way for better, more effective localized therapy. So I see it in those two areas, one is stimulating endogenous populations and the other is cells as delivery vehicles. These applications are in addition to my earlier mention of the use of stem cell based in vitro disease models.  You are already seeing companies in the business of providing specific cell types to biopharma companies for this purpose.  If we can use human cells of interest early in the discovery process and provide  a better front end to the traditional biopharma discovery and development model we hope to be able to change significantly the economics of drug discovery.


Can you talk about the regulatory issues stem cell therapies are and may be in the future and how these issues can inform future study design?

I think the big regulatory challenge is not going to be on the drug side but is going to be on the cell therapy side. For example, we hosted a symposium here last year with several leading researchers in retinal disease who concluded that one of the main things holding back research, as well as regulatory approval, was the ability to track donor cells.  If you're going to inject cells in the eye, in the retina, for example, for AMD or a similar disease, we can’t tell you right now what was the donor contribution and what was the recipient contribution should the eye repair.Obviously if the FDA is going to approve a specific cell therapy, they, the clinician and the patient all want to know what difference and what impact the cell transplant is making.

 So I think all the issues of safety, homing, engraftment, donor versus recipient cell, tumorigenicity, etc., loom large when we’re talking about issues of cell therapy. This likely will be solved in incremental steps in certain ways and that's, for example, why on the cell therapy side you see a lot of action in the MSC space because even if we don't know where the cells go exactly, we know that they don't stay in the body long and there is a lot of clinical experience that they haven’t really done harm. So, I think that's led to the FDA allowing a lot of trials going on whether,as these trials go on to phase 3, they will have large-scale clinical utility is, another question.

 For autologous cell therapy, what it means to be minimally manipulated will also be key. As you know there are some cases this past year where clinics, in the US as well as elsewhere, that were injecting autologous cells into people but asserting that they did not need regulatory oversight because they were under the minimal manipulation threshold.   The FDA said no, wait a minute, that’s not true, you are manipulating them and closed them down. So I think one of the big questions will be, what exactly are the standards of minimal manipulation and, for autologous therapy in a clinical setting, how do we make sure that we can have, for example, a local GMP-like manufacturing capability where you can then ensure all the standardization of not just safety but process repeatability,cell purity and the sort of criteria that regulatory bodies would want to see to ensure a safe and effective therapy. Otherwise, on the regulatory front, I think in terms of either the tools or targets application areas that I was talking about before, it’s pretty straightforward and is just the standard regulatory process.

Thanks for your time, Brock.


For Further reading:

Mason, C., McCall, M.J., Culme-Seymour, E.J., Suthasan, S., Edwards-Parton, S., Bonfiglio, G.A., Reeve, B.C. (2012)

The global cell therapy industry continues to rise during the second and third quarters of 2012. Cell Stem Cell. 11(6):735-9.