T regulatory cells: a key predictor of the host response in mesh - - PowerPoint PPT Presentation

t regulatory cells a key predictor of the host response
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T regulatory cells: a key predictor of the host response in mesh - - PowerPoint PPT Presentation

T regulatory cells: a key predictor of the host response in mesh complications Amanda Artsen, Rui Liang, Leslie Meyn, Steve Abramowitch, Pamela Moalli University of Pittsburgh Medical Center, Magee-Womens Research Institute Disclosures


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T regulatory cells: a key predictor

  • f the host response in mesh

complications

Amanda Artsen, Rui Liang, Leslie Meyn, Steve Abramowitch, Pamela Moalli

University of Pittsburgh Medical Center, Magee-Womens Research Institute

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SLIDE 2

Disclosures

Funding: NIH HD083383 (Moalli) Tobacco Grant Settlement, State of PA I have no other relevant financial relationships to disclose

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SLIDE 3

M2 M1 pain

fibrosis encapsulation

healing

MMPs tissue degradation

exposure M2 M1 tissue integration

mesh implantation

mesh fiber

foreign body response

350,000 urogynecologic mesh surgeries annually

Jonsson et al 2012, 2013 Brown et al 2015 Nolfi et al 2013

Treg Treg ?

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pain

fibrosis encapsulation

M2 tissue integration

350,000 urogynecologic mesh surgeries annually

Jonsson et al 2012, 2013 Brown et al 2015 Nolfi et al 2013

PDGF-BB MCP-1 IGFPB-1 Fibroblasts ? ? ? AIM HYPOTHESIS Treg

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Study design

Patients undergoing mesh excision for pain or exposure Optional biopsy distant from mesh: autologous control No biopsy: biopsy from women undergoing prolapse/SUI surgery matched by age, obesity class and surgical indication = matched control Luminex kit to determine concentrations of MCP-1, PDGF-BB and IGFBP-1 Paired and unpaired t tests

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Results

Exposure (n=8) Pain (n=9) § Age 51.9±12.0y § BMI 28.9±1.0 kg/m2 § Median Parity 3 (IQR 2-4) § All factors were similar between pain and exposure 5 autologous control biopsies 10 matched control biopsies

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Factor (pg/mL) Mesh (n=15) Control (n=15) P value PDGF-BB 0.55±0.29 0.17±0.18 0.001 IGFBP-1 36.11±51.80 39.53±70.64 0.70 MCP-1 2.18±1.15 2.59±5.15 0.76

Results Elevated PDGF-BB in mesh tissue complexes compared to controls

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Conclusions

§ Elevated PDGF in mesh-tissue complexes removed for pain or exposure supports a role of fibroblasts § Similar results in pain and exposure groups suggest same mechanistic pathway of dysregulated wound healing § Future studies: activated fibroblasts, therapeutic role of T cells

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SLIDE 9

Funding: NIH HD083383 (Moalli) Tobacco Grant Settlement, State of PA

Acknowledgements