Stem Cell Therapies for Intervertebral Disc Degeneration: Immune Privilege Reinforcement by Fas/FasL Regulating Machinery
2014
As a main contributing factor to low back pain, intervertebral disc degeneration (IDD) is the
fundamental basis for various debilitating spinal diseases. The pros and cons of current treatment modalities
necessitate biological treatment strategies targeting for reversing or altering the degeneration
process in terms of molecules or genes. The advances in stem cell research facilitate the studies aiming
for possible clinical application of stem cell therapies for IDD. Human NP cells are versatile with cell
morphology full of variety, capable of synthesizing extracellular matrix components, engulfing substances by autophagy
and phagocytosis, mitochondrial vacuolization indicating dysfunction, expressing Fas and FasL as significant omens of
immune privileged sites. Human discs belong to immune privilege organs with functional FasL expression, which can interact
with invasive immune cells by Fas-FasL regulatory machinery. IDD is characterized by decreased expression level
of FasL with dysfunctional FasL, which in turn unbalances the interaction between NP cells and immune cells. Certain
modulation factors might play a role in the process, such as miR-155. Accumulating evidence indicates that Fas-FasL
network expresses in a variety of stem cells. Given the expression of functional FasL and insensitive Fas in stem cells (we
term as FasL privilege), transplantation of stem cells into the disc may regenerate the degenerative disc by not only differentiating
into NP-like cells, increasing extracellular matrix, but also reinforce immune privilege via interaction with immune
cells by Fas-FasL network.
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