Biomedical Engineering Reference
In-Depth Information
HSCs are thought to have some degree of 'plasticity' and under unique condi-
tions (as aforementioned), may be influenced to take on a role not commonly
attributed to them. In the setting of cutaneous injury, HSCs and BM-derived MSCs
are induced to participate in the healing response, whereby they generate a
subpopulation of fibroblasts (BM-derived fibroblasts), capable of collagen pro-
duction.
12,70-85
Mechanisms by which HSCs and BM-derived MSCs give rise to
BM-derived fibroblasts are 'differentiation' and 'transdifferentiation', respec-
tively, with the latter requiring lineage conversion.
Although BM-derived fibroblasts may have collagen-producing capabilities,
their contribution to ECM reconstruction remains to be fully described. While both
subpopulations of fibroblast (dermal and BM-derived) are capable of transcribing
for collagen I, it is thought that only BM-derived fibroblasts can transcribe for
collagen III (an important distinguishing factor for regenerative studies.)
79
In
addition to skin, HSCs also participate in the injury responses of other organs,
including liver, heart and skeletal muscle.
10
Circulating fibrocytes
The process by which HSCs generate progenitors capable of 'transdifferentiating'
into progenitors of BM-derived fibroblasts is not well-understood and remains
controversial. As alluded to earlier, there is some evidence to suggest that circulat-
ing fibrocytes may be an intermediate between HSCs and BM-derived fibroblasts.
27-29,32
Fibrocytes may have plasticity potential and in the context of variable hybrid
phenotypes and associated functions, it is conceivable that they are indeed the
transitional cell of interest.
While much focus on fibrocytes refers to cutaneous wound healing, the strong-
est evidence in support of fibrocytes as an intermediate between HSCs and
summarizes the many elements of fibrocytes and a possible transdifferentiation
pathway.
28
Some observations linking fibrocytes as a transitional form include (1)
early preference for CD34 and CD45 expression, (2) early APC function, (3)
production of migration and proliferation cytokines, (4) sequential downregula-
tion of CD34 and CD45 in response to TGF-
β
1
, coupled with upregulation of
collagen I and
α
-SMA and (5) late production of collagen and collagnase.
89
Endothelial progenitor cells (EPCs)
Although their contribution to cutaneous wound healing is not clearly defined,
BM-derived progenitor cells with angiogenic properties have been described.
69,92-
97
Known as endothelial progenitor cells (EPCs), these cells are known to express
CD34, CD31 (also known as platelet-endothelial cell adhesion molecule one or
PECAM-1), CD144 and VEGF receptors. Furthermore, they express the trans-
cription factor GATA-2 (associated with hematopoiesis.) They are reportedly
