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Stem Cells Moving into the Mainstream of Drug Discovery: Time to Get on Board


Marcie Glicksman, SLAS Symposium Co-Chair
Brigham & Women's Hospital and Harvard Medical School


Kelvin Lam,
SLAS Symposium Co-Chair
Harvard Stem Cell Institute, Harvard University


Much has happened in the field of stem cell research. In fact, we've recently moved past the honeymoon stage, during which, in our unbridled enthusiasm, we felt as though stem cells could solve everything from early stage drug-discovery mistakes to full-blown disease states. Now we're in the stage where it's obvious that stem cells have tremendous promise in a number of different areas, but we also recognize that it will take much more time and work before that promise can be fully realized. Of course, stem cells have been used for therapy—albeit in a very restricted way—since the 1970s, when bone marrow transplants showed that progenitor cells could be harnessed to regenerate failing marrows. These mesenchymal stem cells were also shown to have the potential to differentiate into other cellular lineages, such as vascular epithelial and muscle cells.


More recently, we learned that adult tissues such as skin, muscle, liver, lung and brain also possess tissue-derived progenitor cells. This means the possibility now exists that endogenous tissue-derived stem cells could be stimulated to heal damaged tissues in humans.

The prospect of being able to apply stem cells more broadly is generating tremendous excitement today—but we also know now that before we can successfully do so, we have to better understand the mechanisms and biology involved. Therefore, SLAS presents Screening Stem Cells 2011: From Reprogramming to Regenerative Medicine, September 26-27, 2011, at the Sheraton Boston Hotel in the Back Bay area of Boston, MA. Screening Stem Cells 2011 is part of the SLAS Global Symposia series, designed to provide participants with focused learning, peer connections and access to the latest technologies and services.

We hope that Screening Stem Cells 2011 will serve as a catalyst to help all understand the mechanisms and biology involved. In addition to providing insights into the basic science which will help us progress further, the symposium will feature several groundbreaking experimental applications of stem cells in medicine. We believe this event will be of significant interest to drug-discovery scientists, as well as researchers, technologists and others from academic, government and commercial laboratories.

Clinical/HTS Opportunities

Stem cells hold promise in several key clinical areas that will be explored in detail in the symposium. One is in safety studies. Current techniques involve testing compounds against primary cells pooled from patients, and trying to come up with an "average" from what is really a heterogeneous pool. In contrast, by using a stem cell that differentiates into liver cells, for example, we can normalize the heterogeneity of the variation in these cells. This allows us to ask with more confidence in the preclinical stage whether a compound of interest might be toxic to the liver, in which case we could halt development early on.

Another area of promise is cell therapy. The aim here is to use stem cells to generate specific types of cells—neuronal cells, for example—that can replace diseased cells to help heal conditions such as spinal cord injury or Parkinson's. Earlier studies used lentiviruses or retroviruses to turn somatic cells into induced pluripotent stem cells (iPS) cells—but these viruses proved to be toxic. Today, instead of using viruses, many labs are experimenting with small molecules to see which might be capable of doing the job without causing harm.

Exciting work also is being done in the reprogramming arena to enable the conversion of somatic cells directly into cardiomyocytes, functional neurons and neuronal stem cells—without first having to become stem/progenitor cells—using specific transcription factors (a process known as transdifferentiation).

In a related area, we can now use stem cells to create disease models. In the past, if certain genetic mutations were known to be found in patients with specific diseases, we had to take cells and generate those mutations to try to replicate the disease. Now, we can take cells with mutations from patients, and generate iPS cells containing those mutations and study them directly. These innovations mean that for scientists involved in high-throughput screening (HTS), the stem cell future is bright. HTS can be used to discover small molecules that can replace viruses in the cell production and/or differentiation process. Traditional screeners with years of experience can make a really smooth transition into stem cell drug discovery; we just need to adapt the skills we already have to stem cell screening.

Business Opportunities

The business models session of the symposium will be a panel discussion that will explore the "value side" of stem cell drug discovery, including vendors who supply some of the reagents for stem cell work, and companies looking to commercialize stem cell strategies for the drug-discovery field. Screeners and companies that are currently providing products and services for regular drug discovery will find plenty of opportunities in the emerging stem cell industry, and the session promises to further leverage synergies between the two SLAS sections, as well.

This session offers perspectives from an academic center, an investor, a specialized start-up company and a large pharmaceutical company, all of who will address the potential business models for cell-based screening and drug discovery. The opening presentation describes the rationale for cell-based screening and the ways that economic value can be created. The respective roles of the different participants at different stages of the value chain and how they interact with one another are discussed to set the stage for the individual presentations that follow.

Pulling it All Together

Rudolf-JaenischKeynote speaker Rudolf Jaenisch, MD, a founding member of the Whitehead Institute for Biomedical Research at MIT and a pioneer in the field of stem cells, will set the tone for this scientifically rigorous symposium. In 2007, the Jaenisch lab was one of three labs worldwide that reported successfully taking cells from mouse tails and reprogramming them into induced pluripotent stem cells, by over-expressing four master gene regulators. Later that year, the lab followed up by further manipulating iPS cells to treat sickle-cell anemia in mice, the first proof in principle of therapeutic use of such cells.

In 2008, his lab reported that neurons derived from iPS cells successfully integrated into fetal mouse brains and reduced symptoms in a Parkinson's disease rat model. In another experiment, researchers demonstrated that fully mature, differentiated mouse B cells can be reprogrammed to iPS cells.

In his keynote address, Stem Cells, Reprogramming and Personalized Medicine: Promise, Problems, Reality, Jaenisch will focus on molecular mechanisms of direct reprogramming; the analysis of newly isolated human ES cells (ESCs), which are epigenetically distinct from conventional human ES cells; and novel approaches for the genetic manipulation of human ES and iPS cells. He will also discuss the current limitations of using iPS cells for studying human diseases, and for their eventual use in transplantation therapy.

Kevin-EgganKevin C. Eggan, Ph.D., is associate professor of stem cell and regenerative biology at Harvard University, early career scientist with the Howard Hughes Medical Institute and principal investigator with the Harvard Stem Cell Institute. Eggan's laboratory is pursuing two interlocking areas of investigation: the basic biology of stem cell programming and reprogramming, and the application of the resulting technologies to studies of the neuromuscular system and the diseases—including amyotrophic lateral sclerosis (ALS) and spinal muscular atropy (SMA) that affect it.

To that end, his group looks at both the differentiation of embryonic stem cells into the neural lineage and the reprogramming of commonly available differentiated cell types, such as fibroblasts, into either pluripotent stem cells or cells of therapeutic interest such as spinal motor neurons.

In his keynote address, Eggan is expected to discuss recent advances in stem cell reprogramming and biology that enable the production of spinal motor neurons with control and diseased genotypes, and how these neurons are being used to design in vitro disease models for mechanistic studies and to discover novel small molecule therapeutics.

Interested in Attending?

Registration is open. Respond by August 15 to obtain early registration discounts. There also are discounts available for groups or academic, government or student attendees. Admission to the exhibits is free for all.

Further Reading

The following papers are examples of the steady progress being made in the field of stem cell research over the past decade.

J. A. Thomson, et al. "Embryonic Stem Cell Lines Derived from Human Blastocysts," (1998) Science, 282, 1145.

Takahashi, K., and Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663-676.

Wernig, M., Meissner, A., Foreman, R., Brambrink, T., Ku, M., Hochedlinger, K., Bernstein, B.E., and Jaenisch, R. (2007). In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 448, 318-324.

Mikkelsen, T.S., Hanna, J., Zhang, X., Ku, M., Wernig, M., Schorderet, P., Bernstein, B.E., Jaenisch, R., Lander, E.S., and Meissner, A. (2008). Dissecting direct reprogramming through integrative genomic analysis. Nature 454, 49-55.

Ichida, J.K., Blanchard, J., Lam, K., Son, E.Y., Chung, J.E., Egli, D., Loh, K.M., Carter, A.C., Di Giorgio, F.P., Koszka, K., et al. (2009). A small-molecule inhibitor of tgf-Beta signaling replaces sox2 in reprogramming by inducing nanog. Cell Stem Cell 5, 491-503.

Originally published June 2011 SBS News

July 6, 2011