Biomedical Engineering Reference
In-Depth Information
immune privileged nature of the IVD [
79
,
80
]. Thus, these results suggest that hFCs
may be an appropriate cells source for use to mitigate IDD.
8.1.3 Notochordal Cells
Notochordal cells (NC) can be found in the IVD of many species throughout
their entire lifespan [
25
]; however, in humans these cells disappear after the first
decade of life and this precludes them from being used directly as an alternative cell
source for TE strategies [
81
]. However, research over the last decade has shown that
that the soluble factors produced by NCs possess anabolic characteristics that could
be crucial to the maintenance of a healthy NP [
81
-
85
]. In addition, NC conditioned
media has been shown to stimulate the differentiation of human mesenchymal stem
cells (MSCs) towards an early NP cell-like phenotype in 3D pellet culture [
86
]. Our
group has also observed a similar phenomenon in which MSCs from human adipose
tissue were cultured in monolayer in the presence of conditioned media derived
from a mixed population of porcine NP cells and NCs. The stem cells began
to exhibit gene and protein expression profiles, including the upregulation of
aggrecan, sox-9, and collagen type II, which could be indicative of differentiation
towards an NP cell-like phenotype [
87
].
Due to the transitory nature of the NC population within the human IVD, the use
of this cell population directly for NP TE applications might not be clinically
feasible. Although harvest and expansion of these cells from young cadavers or
the use of transgenic animal donors has been suggested as a possible alternative
[
25
], further investigations of such methods are warranted.
8.1.4 Adult Mesenchymal Stem Cells
One of the most widely investigated and promising alternative cell sources for TE
of the human NP is that of adult MSCs, in particular bone marrow-derived and
adipose-derived stem cells (BMSCs and ADSCs, respectively). Stem cells are aptly
defined as having the capacity for unlimited self-renewal paralleled with the ability
to develop into progenitor cells, which include osteogenic, chondrogenic, and
adipogenic lineages [
88
]. MSCs can be expanded in number in vitro and they
appear to possess the ability to suppress or alter allogeneic immune response
[
89
,
90
]. Coupled with the fact that MSCs can differentiate into a chondrogenic
lineage, many researchers are investigating the ability to direct the differentiation of
MSCs towards an NP cell phenotype utilizing various inductive mechanisms. If
successful differentiation of MSCs into an NP-like cell can be realized, MSCs could
serve as an ideal alternative cell source for TE of the NP. Differentiation of human
BMSCs towards an IVD cell-like phenotype can be accomplished using several
different approaches: high cell density 3D spheroid cultures in the presence of
transforming growth factor beta-3 (TGF-
b
3) [
91
], hypoxia with cell culture media
containing TGF-
b
1
and ascorbic acid [
92
], NP-cell conditioned media [
93
], and 3D
