Biomedical Engineering Reference
In-Depth Information
of, and the bystander support to endogenous cells, are being extensively proposed
as major outcome measure facilitating the choice of the disease target [
118
].
Current potential CNS disease targets include brain stroke, traumatic brain injury
(TBI), SCIs, MS, Alzheimer's disease (AD), Parkinson's disease (PD), and, per-
haps further in the future, mental disorders such as depression, autism, and
schizophrenia [
118
]. Based on the discoveries made at the bench side, these
clinical studies fall into two broad categories: (1) Regeneration/restoration versus
cell replacement, to promote host tissue repair and/or replace missing or damaged
cells, and (2) Therapeutic delivery, to provide therapeutic molecules for neuro-
protection and/or stimulation of repair. And MS, brain stroke and (in part) also SCI
are all diseases in which the stem cell-instructed bystander effects are more likely
desirable.
A big challenge for the future will be the identification of a reliable source of
NPCs. Somatic NPCs have showed some limitations, which include their instrinsic
allogeneicity in clinical settings, a relatively slow growth rate, a progressive
shortening of telomeres and decrease of telomerase activity under scale-up con-
ditions, and consequent limited (phenotypic and genotypic) instability upon con-
tinuous expansion [
10
,
118
]. On the other hand, both pluripotent stem cell- and
pluripotent induced stem cell-derived NPCs represent a highly valuable alternative
whose credibility is under continuous challenge by the development of more and
more reliable protocols of expansion, (neural) induction, and (neural vs. glial)
differentiation. Therefore, while the possibility of having large amounts of in
principle autologous NPCs for clinical applications is indeed work in progress, the
scientific community must not stop our attempts toward the identification of the
mechanisms regulating the NPC-instructed bystander effects, if we want to keep
the rights to properly tailor future NPC therapies and avoid unwanted side effects.
Having established the atypical perivascular (stem cell) niche as surrogate
marker of the capacity of NPCs to find in vivo the way(s) towards certain
microenvironments in vivo where acting as therapeutic weapons, we envisage that
understanding the modalities by which NPCs communicate horizontally to the
cells of the microenvironment has the chances to reveal us a number of basal
(vs. reactive) stem cell functions to be translated into innovative highly clinical
impact therapeutics.
References
1. McKay R (1997) Stem cells in the central nervous system. Science 276(5309):66-71
2. Kriegstein A, Alvarez-Buylla A (2009) The glial nature of embryonic and adult neural stem
cells. Annu Rev Neurosci 32:149-184
3. Lois C, Alvarez-Buylla A (1994) Long-distance neuronal migration in the adult mammalian
brain. Science 264(5162):1145-1148
4. Menn B, Garcia-Verdugo JM, Yaschine C, Gonzalez-Perez O, Rowitch D, Alvarez-Buylla
A
(2006)
Origin
of oligodendrocytes
in the subventricular
zone
of the adult
brain.
J Neurosci 26(30):7907-7918
