MadSci Network: Cell Biology

Re: Why do we use bFGF for maintaining pluripotency of stem cells?

Date: Wed May 7 10:26:00 2008
Posted By: William Gunn, Grad student, The Center for Gene Therapy, Tulane University
Area of science: Cell Biology
ID: 1209928365.Cb

That's an excellent question, Abhishek. Unfortunately, if I, or anyone else, were to tell you we knew the answer, we'd be lying. For a follow-up question, try asking your advisor to explain exactly what a stem cell scientist means by the term differentiation. Unfortunately, different labs have different answers, since differentiation is measured by various kinds of assays.

I can tell you that it's not used for maintenance of pluripotency for all stem cells. For example, although hMSCs proliferate rapidly in the presence of FGF, FGF-treated cultures(in our lab's unpublished observations) do not exhibit tri-lineage differentiation to the same degree that untreated cultures do.

There's growing evidence that there's a switch that turns on either differentiative or proliferative pathways in the cell, so it makes sense to think that a factor that promotes proliferation inhibits differentiation, however, that's not always the case, because the timing of the stimuli is important. In tissue repair in vivo, endogenous stem cells proliferate rapidly in response to inflammatory stimuli(in which MAPK plays a part), but the proliferative response is stopped and differentiation initiated after the initial burst of cell division, once there are enough cells to do the repair. It's not known whether the initial stimuli that promotes cell division in one cellular context then promotes differentiation in combination with the other factors present in the later stages of tissue repair, or if it's cell-cell contact that promotes the differentiation, but this process does occur even in the presence of FGF, so FGF isn't working as a strong differentiation preventative agent in that context.

In vitro, it's used because cells divide more readily when it's present, but as I mentioned, this doesn't necessarily mean that it's promoting the proliferative pathway over differentiation. It could also be that FGF is selecting for a less differentiated sub-population, or FGF could be initiating the tissue repair response I described above, promoting activation of the cells called "transitory amplifying" cells.

I'm sorry I can't give a more definitive answer than that. Here's some further reading, if you're interested:

  • One Strategy for Cell and Gene Therapy: Harnessing the Power of Adult Stem Cells to Repair Tissues PNAS 100supp1:11917
  • Regenerative Medicine By Inder M Verma, F Gage
  • Here's an overview of the "niche" of epidermal cells, written by a graduate student, with a nice explanation of transitory amplifying cells.
  • Here's some related commentary on stem cells and cancer.

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