How are stem cell therapies developed?

In What is the Goal of Stem Cell Research?, we explored ways that stem cells might be used to repair or replace damaged tissues, as well as some of the challenges researchers face when developing new therapies.

Stem cell therapies aren't invented overnight. Each potential therapy starts out as a testable idea based on initial research findings. That idea must be followed up with rigorous research and testing in the lab, which can take years - or even decades - of work. Even if the therapy looks great in lab experiments, it will become a viable treatment only after it is proven safe and effective in human clinical trials.

From ideas to therapies: where do we begin?

The first step is to establish an experimental model - a laboratory-based scenario that simulates the way a stem cell therapy might work in humans. To be useful, an experimental model must possess these features:

• It must accurately reflect the biology of human stem cells.
• It must be reproducible, allowing experiments to be credibly repeated.
• It must be time effective, allowing experiments to be completed, analyzed and repeated within a reasonable time period.

Researchers use two basic experimental models to develop stem cell therapies:

1. Most preliminary experiments are performed using cultured stem cells grown in dishes. These cells come from human tissue samples or from model organisms such as mice or rats.
2. Refined candidate therapies are tested in animal models, such as mice and rats, before being used in human clinical trials.

Here, we'll see how researchers create models for preliminary experiments: cell "lines" that grow in the laboratory. A stem cell line is a continuously dividing population of cells obtained from human or animal tissues. Researchers use both embryonic and adult stem cell lines as experimental models.

Embryonic stem cells

Embryonic stem cell lines are established from embryos shortly after fertilization. To create an embryonic stem cell line, an embryo must be separated into individual cells. A single cell from the embryo is placed in a dish and provided with nutrients and growth factors that stimulate it to divide. The resulting cell line will continue to divide as long as it is kept in a controlled environment and provided with appropriate growth factors to prevent differentiation.

Currently, most embryonic stem cell lines are created using mouse embryos. Researchers are currently evaluating several other sources for embryonic stem cells:

• Embryonic stem cells from IVF embryos. Human embryonic stem cell lines can be derived from embryos created through in vitro fertilization (IVF). Usually, fertilization occurs within a woman's body, but IVF technology has made it possible to carry out fertilization and grow embryos in the laboratory. This technology has made it possible for many otherwise infertile couples to have children. In many cases, however, not all of the embryos created will be used, and the remaining embryos are frozen and stored. These embryos are potential resources for scientific research.

• Embryonic stem cells from therapeutic cloning. Embryonic stem cells can also be created by the same procedure used to clone whole organisms, such as Dolly the sheep. Because of its potential medical uses, this method for creating stem cells is called therapeutic cloning.

  In this procedure, a nucleus from an adult donor cell is inserted into a recipient egg cell from which the nucleus has been removed. The nucleus provides all of the necessary genetic information, in the form of DNA, for a cell to function and divide. The resulting cell is then stimulated to divide as a zygote would, resulting in the growth of embryonic stem cells that are genetically identical to the adult donor cell.

  Therapeutic cloning might be a viable approach to growing an exact tissue match for a patient in need - if the donor nucleus came from the patient, the resulting embryonic stem cell line would be a perfect match.

Adult stem cell lines

Adult stem cell lines isolated from mature tissues are another excellent resource for research studies. Most research is performed using adult stem cell lines from model organisms such as mice and rats, since obtaining adult stem cells from humans can involve invasive surgical procedures.

Supported by a Science Education Partnership Award (SEPA) [No. 1 R25 RR16291-01] from the National Center for Research Resources, a component of the National Institutes of Health, Department of Health and Human Services. The contents provided here are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH.