Biomedical Engineering Reference
In-Depth Information
BM-MSCs,alsoknownasmarrowstromalcellsorcolony-forming
units-fibroblast (CFU-F), were first identified from adult BM by
Friedenstein
et al.
in the late 1960s.
26
,
27
Recently they have been
extensively investigated and have demonstrated their great poten-
tial as an attractive and promising cell source for BTE applications
because of their advantages: (1) MSCs can be easily isolated by the
plastic adhesion method or other antibody selection techniques
28
;
(2) the osteogenic differentiation pathway is quite well defined, and
MSCs have been shown to generate greater bone formation than
fresh BM in preclinical studies
29
−
31
; (3) MSCs and differentiated
MSCsarereportedtobenonimmunogenicandsuitableforallogenic
applications; and (4) cryostorage does not affect the osteogenic
potential of MSCs, a condition that greatly facilitates their storage
and clinical applications.
32
Besides these advantages, they are also
found to play an essential role during bone remodeling and frac-
ture healing
in vivo
. On the one hand, as the common progenitors
for osteoblasts, osteocytes, and bone-lining cells, MSCs can affect
bone remodeling via modulating their differentiation into these few
types of osteogenic cells
33
,
34
; on the other hand, they are involved
in bone remodeling through the regulation of the opposing action
ofosteoblastsandosteoclasts.
35
Duringbonefracturehealing,MSCs
can induce new bone formation by cellular differentiation into the
osteoblasts and chondroblasts; moreover, MSCs were found to be
abletocreatearegenerativemicroenvironmentviatheirexpression
of a large spectrum ofbioactivemolecules.
35
−
37
There are certain drawbacks that limit the clinical application of
adult BM-derived MSCs, such as their low existing frequency in BM,
high cellular senescence, limited proliferation capacity during the
expansion,
38
,
39
and decreased osteogenic potential with ages.
40
−
42
As a result, efforts have been made to look for an alternative source
of MSCs, and these efforts have led to the successful identification
andisolationofMSCswithosteogenicpotentialfromadiverserange
of ontological and anatomical sources, including postnatal tissue
such as adipose tissue,
43
periosteum,
44
trabecular bone,
45
synovial
membrane,
46
and peripheral blood
7
; perinatal tissues such as the
umbilical cord,
48
umbilical cord blood,
49
,
50
and amniotic fluid
51
,
52
;
and prenatal tissue like fetal blood, BM, and liver.
53
−
56
While inves-
tigations into their basic biology, immunogenicity, and osteogenic
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