| Title |
Immunomodulatory Effects of Human Cryopreserved Viable Amniotic Membrane in a Pro-Inflammatory Environment In Vitro
|
|---|---|
| Published in |
Cellular and Molecular Bioengineering, August 2017
|
| DOI | 10.1007/s12195-017-0494-7 |
| Pubmed ID | |
| Authors |
Claire E. Witherel, Tony Yu, Mark Concannon, Will Dampier, Kara L. Spiller |
| Abstract |
Chronic wounds remain a major clinical challenge. Human cryopreserved viable amniotic membrane (hCVAM) is among the most successful therapies, but the mechanisms of action remain loosely defined. Because proper regulation of macrophage behavior is critical for wound healing with biomaterial therapies, we hypothesized that hCVAM would positively regulate macrophage behavior in vitro, and that soluble factors released from the hCVAM would be important for this effect. Primary human pro-inflammatory (M1) macrophages were seeded directly onto intact hCVAM or cultured in separation via transwell inserts (Soluble Factors) in the presence of pro-inflammatory stimuli (interferon-γ and lipopolysaccharide) to simulate the chronic wound environment. Macrophages were characterized after 1 and 6 days using multiplex gene expression analysis of 37 macrophage phenotype- and angiogenesis-related genes via NanoString™, and protein content from conditioned media collected at days 1, 3 and 6 was analyzed via enzyme linked immunosorbent assays. Gene expression analysis showed that Soluble Factors promoted significant upregulation of pro-inflammatory marker IL1B on day 1 yet downregulation of TNF on day 6 compared to the M1 macrophage control. In contrast, intact hCVAM, which includes both extracellular matrix, viable cells, and soluble factors, promoted downregulation of pro-inflammatory markers TNF, CCL5 and CCR7 on day 1 and endothelial receptor TIE1 on day 6, and upregulation of the anti-inflammatory marker IL10 on day 6 compared to the M1 Control. Other genes related to inflammation and angiogenesis (MMP9, VEGF, SPP1, TGFB1, etc.) were differentially regulated between the Soluble Factors and intact hCVAM groups at both time points, though they were not expressed at significantly different levels compared to the M1 Control. Interestingly, Soluble Factors promoted increased secretion of the proinflammatory cytokine tumor necrosis factor-α (TNF-α), while direct contact with hCVAM inhibited secretion of TNF, relative to the M1 Control. Both Soluble Factors and intact hCVAM inhibited secretion of MMP9 and VEGF, pro-inflammatory proteins that are critical for angiogenesis and remodeling, compared to the M1 Control, with intact hCVAM having a stronger effect. In a simulated pro-inflammatory environment, intact hCVAM has distinct anti-inflammatory effects on primary human macrophages, and direct macrophage contact with intact hCVAM is required for these effects. These findings are important for the design of next generation immunomodulatory biomaterials for wound repair and regenerative medicine that may include living cells, soluble factors, or a controlled drug delivery system. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 33% |
| Practitioners (doctors, other healthcare professionals) | 1 | 33% |
| Science communicators (journalists, bloggers, editors) | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 37 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 6 | 16% |
| Researcher | 6 | 16% |
| Student > Master | 6 | 16% |
| Student > Bachelor | 2 | 5% |
| Student > Postgraduate | 2 | 5% |
| Other | 5 | 14% |
| Unknown | 10 | 27% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 7 | 19% |
| Engineering | 5 | 14% |
| Biochemistry, Genetics and Molecular Biology | 4 | 11% |
| Agricultural and Biological Sciences | 3 | 8% |
| Chemical Engineering | 2 | 5% |
| Other | 5 | 14% |
| Unknown | 11 | 30% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 December 2017.
All research outputs
#14,079,280
of 22,999,744 outputs
Outputs from Cellular and Molecular Bioengineering
#233
of 460 outputs
Outputs of similar age
#169,970
of 317,467 outputs
Outputs of similar age from Cellular and Molecular Bioengineering
#8
of 16 outputs
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So far Altmetric has tracked 460 research outputs from this source. They receive a mean Attention Score of 3.2. This one is in the 46th percentile – i.e., 46% of its peers scored the same or lower than it.
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