EFFECT OF SCAFFOLDS WITH BONE GROWTH FACTORS ON NEW BONE FORMATION - Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine - page 890

potential have been reported, MSCs from different sources have not
been systematically compared for BTE applications. Therefore, we
performedastudytosystematicallycomparehumanMSCsfromdif-
ferent ontological and anatomical origins, including fetal BM, the
umbilical cord, adult BM, and adult adipose tissue. 57 These four
types of MSCs were compared head-to-head for their proliferation
capacity and osteogenic potential mineralization in vitro under two
differentculturesystemsettings,bothamonolayercultureanda3D
polycaprolactone-tricalcium phosphate (PCL-TCP) scaffolds (manu-
facturedbyOsteoporeIntPteLtd.,Singapore)culture,andthe in vivo
ectopicboneformationcapacityofdifferentMSC-mediatedscaffolds
wasinvestigatedaswell.
Our study unveiled the profound influence of the ontological
and anatomical origin on cellular performance of MSCs for BTE
applications. Human fetal MSCs (hfMSCs), derived from BM and an
ontologically primitive origin, demonstrated their great potential as
a superior cellular source for BTE applications. They demonstrated
theirprimitivenessbyexpressingembryonicstemcellmarkerssuch
as Oct-4and Nanog.
In the monolayer culture, when compared with other MSCs,
hfMSCs proliferated much faster (1.5-3.4x, p < 0.01) with signifi-
cantly higher self-renewal capacity (1.6-2.0x, p < 0.01), as deter-
mined by the CFU assay (Fig. 43.16a). In the 3D PCL-TCP scaffold
culture, Picogreen dsDNA quantification assay showed that hfMSCs
proliferated much faster and saturated all the empty spaces in the
scaffoldswithin7days,whileittook28daystoachievecellularcon-
ference for other MSCs(Fig. 43.16b).
The hfMSCs can also proliferate for more than 100 population
doublings before reaching cellular senescing, while human adult
BM-derived MSCs (haMSC) can only sustain for 30 population dou-
blings. Furthermore, hfMSCs have the highest osteogenic potential,
both in vitro and in vivo , among the four types of MSCs, as assessed
by von-Kossa staining, scanning electron microscopy (SEM) scan-
ning ALP activity, and micro CT quantification of the ectopic bone
formation in vivo (Fig. 43.17). 57 In addition, our study showed a
lower HLA-1 expression in hfMSCs than other MSCs (55% vs. 95%-
99%), indicating their lower immunogenicity. This is in consistence
with a number of recent studies showing that hfMSCs have lower