Monday, 4 November 2013

LIF and stem cells

Laterza C, Merlini A, De Feo D, Ruffini F, Menon R, Onorati M, Fredrickx E, Muzio L, Lombardo A, Comi G, Quattrini A, Taveggia C, Farina C, Cattaneo E, Martino G. iPSC-derived neural precursors exert a neuroprotective role in immune-mediated demyelination via the secretion of LIF. Nat Commun. 2013 Oct 29;4:2597. doi: 10.1038/ncomms3597.

The possibility of generating neural stem/precursor cells (NPCs) from induced pluripotent stem cells (iPSCs) has opened a new avenue of research that might nurture bench-to-bedside translation of cell transplantation protocols in central nervous system myelin disorders. Here we show that mouse iPSC-derived NPCs (miPSC-NPCs)-when intrathecally transplanted after disease onset-ameliorate clinical and pathological features of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Transplanted miPSC-NPCs exert the neuroprotective effect not through cell replacement, but through the secretion of leukaemia inhibitory factor that promotes survival, differentiation and the remyelination capacity of both endogenous oligodendrocyte precursors and mature oligodendrocytes. The early preservation of tissue integrity limits blood-brain barrier damage and central nervous system infiltration of blood-borne encephalitogenic leukocytes, ultimately responsible for demyelination and axonal damage. While proposing a novel mechanism of action, our results further expand the therapeutic potential of NPCs derived from iPSCs in myelin disorders.

So the belief that stem cell transplants will turn into new nerves oligodendrocytes is not found and the stem cells that can be grown from any cell (iPS cells) work by secreting growth factors that stimulate cells already in the CNS to become remyelinating cells. This is obtained from the  action of leukaemia inhibitory factor  a growth factor known to affect oligodendrocyte maturation but inhibits stem cell differentiation. This cytokine can also inhibit immune cell function, so how much is the effect remyelination and how much immunomodulation. Both would be good. This further indicates that the beneficial effect is drugable and that changing the CNS microenvironment to promote repair rather than cell replacement is likely to be the most productive way forward 


    Dr. Miller at Case Western Reserve published on hepatocyte growth factor and its effect on promoting MSCs growth and differentiation. Evidence is mounting that changing microenvironment in CNS is effective in promoting endogenous repair mechanisms. The question is: Which method would be more effective, introducing cell-free factors or using stem cell transplants to secrete these factors?

  2. If you can use cell free factors it will be a lot easier.


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