Bone marrow stromal cells in myocardial regeneration and the role of cell signaling - Artificial Cells, Cell Engineering and Therapy - page 147

Because of such differences, it is often difficult to compare the findings
among different studies. 35 Standardization of such classifications is of para-
mount importance as it will be very helpful in the further exploration of the
mechanisms of MSC differentiation. One possible reason behind this confusion
might be because only fully mature cells can be characterized by a defined set of
specific markers. In fact, because of their undifferentiated state, a constantly
changing set of markers may be continuously defining the `labile' phenotype of
MSC.

6.3.2 Pathophysiological role of MSC in cardiac injury

In contrast to the ES cells, whose goal is to develop a new organism, cumulative
information gathered during the past several years suggests that adult stem cells
participate in tissue growth and repair throughout postnatal life. 38,39 In fact, there
is currently ample evidence suggesting that MSC can be recruited from the BM to
various tissues to participate in tissue repair and regeneration in response to either
apoptosis or tissue injury. 40,41 In fact, progenitor stem cells have been shown to
be recruited from the BM to contribute to angiogenesis in wound healing,
vascularization post-myocardial ischemia, and even growth of certain tumors. 42
A hypothesis driven by our laboratory to explain the role of MSC in the bone
marrow is that they serve as `reserve' cells to participate in tissue repair when
needed. 43 Indeed, several studies have shown that MSC differentiation occurs
almost exclusively in organs that have been damaged. For instance, differentia-
tion to endothelial cells, hepatocytes and myoblasts is seen in cases of ischemia,
cirrhosis and muscular dystrophy. 26,44,45 In this case, it is hypothesized that upon
injury, stem cells can proliferate in vivo and are then recruited to the injured
environment. There, they will differentiate in response to local cues 38,46

(see

below).
Several pieces of evidence published in the last several years has confirmed
this pathophysiological role of marrow-derived adult stem cells. Orlic and his
group have shown that labeled MSC can be mobilized within hours of
myocardial infarction to home to the injured myocardium. 47 Furthermore, by
using a coronary artery ligation model, Bittira et al. from our laboratory, 38
demonstrated that in response to a myocardial injury, labeled MSC are recruited
from the bone marrow, and travel through the circulation to home to the peri-
infarct area within hours to days. In the following weeks, these MSC underwent
`milieu-dependent' differentiation and expressed various phenotypes including
cardiomyocytes, myofibroblasts, endothelial and smooth muscle cells. Our
hypothesis is that each type of cell is somehow involved in the pathophysio-
logical process following myocardial infarction. For instance, newly formed
endothelial cells can participate in the process of angiogenesis; cardiomyocytes
can functionally integrate into the myocardium; and myofibroblasts can
contribute to scar maturation, which favorably alters the remodeling process.