GMP Stem cells

A recent press release by the California Institute of Regenerative Medicine announced the award of $6 million to the lab of Xianmin Zeng, Ph.D., of the Buck Institute for Age Research and The City of Hope, a small biotech research/treatment center in Californina, to generate human stem cells that may one day be suitable for clinical treatment in Parkinson's. What Dr. Zeng's lab has accomplished - and now has funding to try on a large scale - is the ability to grow and differentiate stems cells using defined culture conditions - an important aspect of Good Manufacturing Practice (GMP) that the US Food and Drug Administration (FDA) requires for any compound that will be used for human therapeutics.

What does "defined" mean? It simply means that one knows exactly what compounds are added to the culture media -- the fluid used to grow and nuture cells. Typically, when scientists grow cells for research use, they use undefined conditions where they don't know exactly what the fluid contains. For example, if you are cooking something that requires a banana flavor, you could chose the defined route of just using banana flavoring in a bottle, which is a single chemical called isoamyl acetate. Alternatively, you could choose the undefined route and use a whole banana, which not only contains isoamyl acetate but a whole bunch of unknown chemicals and proteins.

Why does this matter? Replication and Safety.

• Replication: Because you don't know exactly what is contained in undefined media, it can be difficult to replicate. A classic example is from the early days of heart physiology. Many early advances in the field were made by Sydney Ringer. He created a defined media but used London tapwater as the source. He ran into difficulty trying to replicate his own experiments using distalled water. Turns out London tapwater has trace amounts of calcium which is essential for normal heart function...and he revised the formula for his now famous Ringer's saline solution.

• Safety: The safety issue centers around the fact that cells in culture often need various proteins and growth factors...not all of them are known. For research, the convenient answer is to use an undefined media, often this mean using an animal derived serum. Another approach has been to use what are called "feeder cells" which also provide the trace amounts of proteins and growth factors to keep stem cells alive. However, both approaches can expose stem cells to nasty foreign biologic material like viruses (both known and unknown) that could be devisatating if subsequently transplanted in to people.

So the advance Dr. Zeng's lab has made in creating GMP-compliant culture conditions is an important step in moving stem cells closer to use in human therapy.