Biomedical Engineering Reference
In-Depth Information
12.4.4.1 Drugs That Have Immunomodulatory Effects on T Cells and Dendritic
Cells A new group of tyrosine kinase inhibitors, exemplified by the Bcr-Abl
inhibitor imatinib, avoids the side effects of systemic chemotherapies and the
high morbidity and mortality risks associated with HSC transplantation. Concur-
rently, however, increasing evidence has emerged to indicate that these drugs exert
profound immunomodulatory effects on T cells and antigen-presenting cells, such as
dendritic cells, that play major roles in immune tumor surveillance and the outcome
of HSC transplantation. Targeted tyrosine kinase inhibitor therapy may thus control
cancer cell growth both directly and indirectly by changing the immunologic
microenvironment. Furthermore, such molecules might help to unravel the com-
plexities of the human infectious processes.
12.4.4.2 Immunomodulatory Properties of Mesenchymal Stem Cells Derived from
Dental Pulp and Dental Follicle are Susceptible to Activation by Toll-Like
Receptor Agonists Adult MSCs have recently become a potent tool in regenerative
medicine. Because of certain shortcomings of obtaining bone marrow MSCs,
alternate sources of MSCs have been sought. MSCs from dental pulp (DP-MSCs)
and dental follicle (DF-MSCs), isolated from the same tooth or donor, to define
differences in their phenotypic properties, differentiation potential, and immuno-
modulatory activities. Both cell types showed colony-forming ability and expressed
typical MSCs markers but differed in the levels of their expression. DF-MSCs
proliferated faster, contained cells larger in diameter, and exhibited a higher potential
to form adipocytes and a lower potential to form chondrocytes and osteoblasts
compared with DP-MSCs.
In contrast to DF-MSCs, DP-MSCs produced TGF-
and suppressed proliferation
of peripheral blood mononuclear cells (PBMCs), which could be neutralized with
anti-TGF-
b
b
antibody. The treatment with Toll-like receptor 3 (TLR3) agonist
augmented the suppressive potential of both cell types and potentiated TGF-
b
and interleukin-6 secretions by these cells. TLR4 agonist augmented the suppressive
potential of DF-MSCs and increased TGF-
production but abrogated the immuno-
suppressive activity of DP-MSCs by inhibiting TGF-
b
production and the expression
of indolamine-2,3-dioxygenase-1. Some of these effects correlated with the higher
expression of TLR3 and TLR4 by DP-MSCs compared with DF-MSCs. Dental
MSCs are functionally different, and each of these functions should be further
explored in vivo before their specific biomedical applications are used.
b
12.5 APPLICATION
12.5.1 Routes of Application
Progenitor cells for cardiac repair can be delivered in different ways via the
intracoronary route or by direct injection into the myocardium using a percutaneous
catheter-based or surgical epicardial approach. Intracoronary infusion using standard
balloon catheters has been used in all clinical trials treating patients with acute
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