Stem cells and progenitor cells

Reynolds had dropped out of research in 1997, taking a degree in oriental medicine, and was making a living as an acupuncturist and herbal therapist on a small island off Vancouver, while at the same time working for biotech StemCell Technologies.

In 2004 Rietze enticed his friend back into research with an offer to work as a visiting scientist at QBI. Reynolds brought with him an uncompleted project, a new assay that could discriminate stem cells from their more restricted progeny, the progenitor cell.

The collaboration that ensued between Dr Sharon Louis (still with StemCell Technologies), Rietze and Reynolds (now promoted to full professor) resulted in the development of the neural colony forming cell assay (N-CFCA).

On January 24 this year, Louis, Rietze and Reynolds and their QBI and StemCell Technologies colleagues published details of their new neural stem cell assay in the on-line edition of Stem Cell Express.

When a neural stem cell divides, it can either form two new neural stem cells (symmetrical division) or a neural stem cell and an NPC (asymmetrical division).

When an NPC is formed, it migrates to a specific tissue or region of the brain where locally secreted growth factors direct it to differentiate into a specialised neuron, glial cell, oligodendrocyte or astrocyte. At each either-or node along its path towards terminal differentiation, it becomes more "mortal" - only true neural stem cells continue to divide for the individual's lifetime.

True neural stem cells and NPCs both form neurospheres, but after several weeks the growth rate of NPC-derived neurospheres declines, and they fall off the pace.

Rietze says that the new neural colony-forming cell assay (N-CFCA), distinguishes true neural stem cells from NPCs by the size of the colonies they form: NPCs give rise to small colonies, NSCs to large colonies. At 21 days, any colony less than 2mm in diameter comprises NPCs.

The new assay confirms that the number of true neural stem cells in the brain is much smaller than originally estimated.

It also suggests that some1300 research papers published since the original neurosphere assay came into use in the mid-1990s are potentially wrong, because they counted mixed populations of true neural stem cells and neural progenitor cells.

Quoting Mark Twain, Rietze observes, "It ain't what you don't know that gets you into trouble. It's what you know for sure that just ain't so."

Many previous studies used epidermal growth factor (EGF) to expand neural stem cell populations in vitro. It turns out that one of the few differences between neural stem cells in the test tube versus in the mouse is that neural stem cells do not divide in response to EGF in vivo - making a number of EGF-related stem cell therapies (based on in vitro results) misleading