Alterations in the Secretome of Clinically Relevant Preparations of Adipose-Derived Mesenchymal Stem Cells Cocultured with Hyaluronan
Table 1
Summary of cytokines across all conditions.
Cytokines
Fold change from control (CI = 95%)
Role in OA
SVF day 1
SVF day 3
SVF + adipo day 1
SVF + adipo day 3
MSC seeding
MSC media
Proinflammatory
MIF
0.94
0.93
0.89
0.99
1.49
0.79
Induce the release of proinflammatory cytokines, such as TNF-, IFN-, IL-1, IL-6, and IL-8 [6] and MIF levels in synovial fluid correlate to OA severity [7]
Highly expressed in OA-derived human articular cartilage [9]
IL-1β
1.03
1.12
0.59
0.89
1.00
0.94
Induce inflammatory reactions and catabolic effects independently as well as in combination with other mediators in OA with respect to the articular cartilage [10]
IL-12
0.67
0.86
0.49
0.78
1.00
0.90
Expressed by infiltrating macrophages and synovial cells in OA [11]
IL-17
0.70
1.17
0.83
0.90
0.96
0.09
Inhibit the synthesis of proteoglycans in OA and upregulate catabolic enzymes which break down cartilage [10]
IFN-
0.96
0.86
0.89
0.80
0.99
0.93
Stimulate cartilage breakdown by production of enzymes via IL-1β [12]
Anti-inflammatory/dual role
IL-10
0.90
0.85
0.40
0.61
1.05
0.86
Expressed in chondrocytes and involved in collagen and aggrecan synthesis. Inhibition of catabolic enzymes and apoptosis of chondrocytes [10]
IL-2
0.81
2.35
0.69
0.74
1.23
1.35
Elevated levels are found in OA synovial fluid and increased levels correlate to increase severity [13]
IL-6
0.93
0.84
0.47
0.94
1.11
0.84
Catabolism aggrecan via aggrecanase activity [14] involved in the synthesis of tissue inhibitor of metalloproteinases known to stop cartilage breakdown [15]
Chemokines
GROα
1.02
0.89
0.79
0.87
0.94
1.12
Constitutively secreted by chondrocytes and secretion of this chemotactic protein is increased in stimulated osteoarthritic chondrocytes and synovial fibroblasts [16]
MIP-1β
0.92
0.83
0.86
1.17
1.16
1.14
Present in significantly higher levels in OA synovial fluid compared to normal synovial fluid [17]
RANTES
0.78
0.99
0.94
1.31
1.09
0.67
Secreted by IL-1 stimulated osteoarthritic chondrocytes and TNF-α stimulated synovial fibroblasts [16]
MCP-1
0.79
0.65
0.75
0.90
0.95
0.91
Constitutively expressed in osteoarthritic chondrocytes and increased secretion in IL-1 stimulated osteoarthritic chondrocytes [16]
MCP-3
0.83
1.07
0.82
0.95
0.97
N.D.
Activate immune cells such as monocytes, T lymphocytes, basophils, and eosinophils [18]
MIP-1α
0.83
0.67
0.82
0.90
1.04
0.95
Expressed by osteoarthritic derived chondrocytes and production is enhanced by TNF-α stimulated chondrocytes [19]
Growth factors
HGF
0.69
0.83
0.83
1.56
1.42
0.95
Promote osteophyte formation via MCP-1 mediated infiltration of immune cells into OA affected joint [20]
FGF-β
0.89
1.21
0.79
0.98
1.26
0.84
Potentiate articular cartilage resurfacing and may stimulate expression of MMP-13 [21, 22]
β-NGF
1.02
0.92
0.73
0.86
0.78
0.86
Higher expression is found in osteoarthritic derived chondrocyte compared to healthy chondrocytes [23]
GM-CSF
0.84
1.82
0.76
0.91
1.38
N.D.
Key mediator in inflammation and arthritic pain [24]
VEGF
0.71
0.82
0.51
0.71
1.00
0.84
Expressed in osteoarthritic-derived chondrocytes and shown to increase osteochondral angiogenesis in OA patients [25]
G-CSF
0.97
0.96
0.51
0.80
1.06
0.84
Can significantly increase nitrite levels in cartilage when combined with IL-1β explants [26]
A summary of cytokines across all the conditions treated with HA. The data is represented as fold change in concentration compared to control. A value more than one indicates the HA treatment increased the secretion of that cytokine in that condition. Bold values represent a significant fold change from control determined numerically using confidence interval set at 95%. Italic values were only detected in one of the three biological replicates for that condition.
