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Delivering on the promise of human stem-cell research. What are the real barriers?

Melissa Little1, Wayne Hall1, 2 & Amy Orlandi1, 2



1 Melissa Little, Wayne Hall and Amy Orlandi are at the Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
e-mail: m.little@imb.uq.edu.au
2 Wayne Hall and Amy Orlandi are also at the School of Population Health at the University of Queensland.


last part:

Sixth, the most economically successful products are those that can be widely distributed and do not require individualization for each patient. Despite the alleged advantages of generating autologous cells from ASCs, such treatments would undoubtedly be less economically feasible. By contrast, products such as the mesenchymal stem cells of Osiris Therapeutics (Baltimore, MD, USA) might be applicable to all patients: these cells are immunomodulatory, will not be rejected and have broad plasticity (Taupin, 2006). The increasing availability of efficacious immunosuppressant drugs will also make non-autologous treatments more acceptable and probably more cost-effective in the future.

But there are already some promising developments. A research team at the University of Düsseldorf, Germany, has developed a therapy, on the basis of ASCs, in which autologous bone marrow cells are injected into the hearts of infarct patients. Results show that, after several months, the therapy leads to myocardial regeneration and neovascularization, thus improving cardiac function in both acute and chronic heart disease (Brehm & Strauer, 2006; Strauer et al, 2002).

However, until more pharmaceutical companies make bold attempts to develop successful stem-cell-based therapies, risk aversion among potential investors is a real barrier to realizing the benefits of this research. Despite the ethical, legal and regulatory uncertainty, most large biotechnology and pharmaceutical companies are watching this space closely and have, or are developing, in-house research teams to evaluate stem cells as a potential product.

The final two barriers that are often overlooked are people and time. Why has there been such little progress despite the fact that it is legal to derive hESC lines and use SCNT in the UK, South Korea and Israel? The reasons become clear if we take a closer look at hESCs. The equivalent murine cell type has been available for some 25 years, primarily as a research tool to recreate models of human disease rather than as a way to develop cellular therapies (Evans & Kaufman, 1981; Martin, 1981). Nonetheless, the derivation and manipulation of murine stem cells was an elite skill for many years. It is less than a decade since the first derivation of a hESC line (Thomson et al, 1998), and the difficulties of culturing these cells to maintain their pluripotency—as can be done for mouse ESCs (Gearing et al, 1987; Gough et al, 1988)—has made the manipulation of hESCs an even more highly skilled art and one that few scientists have yet mastered. A major limitation on the field of hESC research is, therefore, a shortage of human research skill that can only be overcome slowly.

In the area of ASCs, 35 years of research into haematopoietic stem cells have now defined the questions that must be answered to decide whether an adult cell is a stem cell. Each new potential ASC source will need to be similarly assessed for self-renewal, long-term genetic stability, multipotentiality and potential to regenerate its own organ of origin. This will require the development of novel assays specific to that cell or organ. It is therefore unrealistic to imagine that advances in the understanding of new sources of ASCs will occur within a few years, when it has taken so long to characterize the few ASCs that we use at present. Progress in this field will take time and considerable investments in human resources.
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In conclusion, it is still unclear which human stem cells—whether embryonic or adult—will be developed and for which conditions. Given this, the focus of the NIH in the USA, and research organizations in other countries, should be on developing human research capacity in both ASCs and ESCs. Each type of research will take time to mature. The ethical debate will need to produce acceptable policy and regulatory compromises so that the regulatory burden can be reduced and investors' risk aversion can be overcome. If these things happen, the major remaining barrier to realizing the medical benefits of stem-cell research might be the lack of skilled scientists in the field.