Biomedical Engineering Reference
In-Depth Information
platelet-derived growth factor (PDGF) family have been used to induce or enhance
differentiation of adult stem cells. The identification of subsets of adult stem cells
with a higher capacity to differentiate into cardiac myocytes is currently under
investigation. Progenitor cells may improve neovascularization and thereby augment
nutrients and oxygen supply. Neovascularization can be mediated by the physical
incorporation of progenitor cells into new capillaries or by perivascular accumula-
tion of cells. Incorporated progenitor cells of most, if not all, types may release
growth factors that promote angiogenesis by acting on mature endothelial cells.
Paracrine factors may also beneficially influence cardiac repair by protecting
cardiomyocytes from apoptotic stimuli or activate cardiac resident stem cells to
enhance the endogenous repair capacity. The release of various cytokines affects the
cardiac remodeling processes by altering the development of fibrosis development
during scar formation or by modulating inflammatory processes .The extent to which
progenitor cells contribute to vasculogenesis depends on the environment to which
the cells are exposed. Thus stem cells mechanisms to be considered include trans-
differentiation of stem cells, enhanced neovascularization, alterations in scar for-
mation, and cytoprotection.
12.4.4 Immunomodulatory Effect of Stem Cells
Numerous studies have demonstrated that human mesenchymal stem cells (hMSCs)
avoid allorecognition, interfere with dendritic cell and T-cell function, and generate a
local immunosuppressive microenvironment by secreting cytokines. It has also been
shown that the immunomodulatory function of human MSCs is enhanced when the
cells are exposed to an inflammatory environment characterized by the presence of
elevated local interferon-
) levels. Other studies contradict some of these
findings, reflecting both the highly heterogeneous nature of MSC isolates and the
considerable differences between isolates generated by the many different methods
under development.
Mesenchymal stem cells are multipotential nonhematopoietic progenitor cells
capable of differentiating into multiple mesenchymal tissues. hMSCs are character-
ized by a low expression of major histocompatibility complex (MHC) class I and the
absence of co-stimulatory molecules such as CD80, CD86, or CD40. Moreover,
hMSCs fail to induce proliferation of allogeneic or xenogeneic lymphocytes.
These characteristics support the possibility of exploiting universal donor MSC
for therapeutic applications. MSCs constitutively express low levels of MHC-I
molecules, but, as a general rule, they do not constitutively express MHC class II
molecules However, recent evidence indicates that MSC can function as antigen-
presenting cells and activate immune responses under appropriate conditions.
Although one study reported constitutive MHC class II expression on MSC, several
groups reported that both MHC class I and class II molecules are upregulated after
IFN-
g
(INF-
g
treatment, thus inducing a T-cell response to recall antigens.
Mesenchymal stem cells have an immunomodulatory effect, which is currently
being exploited in the clinical setting for the treatment of coronary artery
diseases.
g
Search WWH ::
Custom Search