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The Use of Exogenous Adenosine Triphosphate (ATP) to Stimulate the Growth of Human Tissue Engineered Cartilage (pp. 99-122) $100.00
Authors:  (Jennifer K. Bow, Stephen D. Waldman, Department of Mechanical and Materials Engineering, Queen's University, Kingston, Canada, and others)
Abstract:
The formation of cartilaginous tissue in vitro is a promising approach for the repair
of damaged articular cartilage as a result of trauma or disease (e.g. osteoarthritis). It has
been challenging, however, to engineer articular cartilage constructs suitable for joint
resurfacing as the engineered tissues typically do not possess similar properties to that of
native cartilage. One approach to develop functional tissue constructs has been through
the application of mechanical stimuli which is based on the premise that the mechanical
environment is involved in the development and maintenance of articular cartilage in
vivo. Although this method has been highly successful, there are potential limitations to
translate this approach to stimulate anatomically-shaped constructs required for effective
joint resurfacing. However, by harnessing the underlying mechanotransduction pathways
responsible, it may be possible to elicit similar effects in the absence of externally applied
forces. While we have shown previously that direct stimulation of the purinergic receptor
pathway by exogenous adenosine triphosphate (ATP) can improve the formation and
properties of engineered cartilage constructs in animal models, the effectiveness of this
approach on human chondrocytes is currently unknown. In this study, human
chondrocytes obtained from donors undergoing total joint arthroplasty (N = 22) were
grown in 3D scaffolds and stimulated with exogenous ATP in concentrations ranging
from 50 nM to 1 mM. While exogenous ATP stimulation was found to increase matrix
synthesis by 170% (over control) at doses between 100 nM to 1 μM, 28% of the donors
failed to respond positively to the stimulus. Further examination of P2Y receptor
expression by flow cytometry (N = 8) revealed varied expression and heterogeneity of
P2Y1 and P2Y2 receptors amongst the donors and that there was a positive correlation
between receptor profile and ATP half-life; however, these differences did not correlate
to the observed response to exogenous ATP. Patient demographics appeared to correlate
with the observed response as patients who had a history of cigarette smoking, worse
arthritis patterns, and/or chronic opioid therapy were more likely to elicit a negative
response to ATP stimulation. Therefore, stimulation of human engineered cartilage by
exogenous ATP appears to be a promising technique for improving tissue formation;
however, its effectiveness is highly dependent on the characteristics of the individual
donor. 


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The Use of Exogenous Adenosine Triphosphate (ATP) to Stimulate the Growth of Human Tissue Engineered Cartilage (pp. 99-122)