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Mesenchymal stem cells in emphysema


- candidate number23712
- NTR NumberNTR5664
- ISRCTNISRCTN no longer applicable
- Date ISRCTN created
- date ISRCTN requested
- Date Registered NTR3-feb-2016
- Secondary IDs2015/599 METc Universitair Medisch Centrum Groningen
- Public TitleMesenchymal stem cells in emphysema
- Scientific TitleMesenchymal stem cells in emphysema:finding the right niche for alveolar repair
- ACRONYM
- hypothesis
- Healt Condition(s) or Problem(s) studiedCOPD, Empyema, Mesenchymal stem cells
- Inclusion criteriaLung resection material will be obtained from COPD patients and nonCOPD controls, who undergo lung transplantation or lobectomy / pneumectomy because of lung cancer. COPD patients will be selected on basis of having smoked more than 20 pack years and having clinical signs of emphysema. Written informed consent will be collected from all patients in order to be eligible for inclusion. The nonCOPD controls will be selected on basis of having smoked less than 1 pack year and having no clinical signs of emphysema. Lung cancer patients who undergo lobectomy / pneumectomy will be selected on basis of the size and location of the tumor, enabling adequate collection of tissue material, without interfering with routine oncopathology procedures.
- Exclusion criteriaPatients with alpha1antitrypsin deficiency will be excluded.
- mec approval receivedno
- multicenter trialno
- randomisedno
- group[default]
- Type2 or more arms, non-randomized
- Studytypeobservational
- planned startdate 1-mrt-2016
- planned closingdate1-mrt-2021
- Target number of participants20
- Interventions1. Central bronchial biopsies of the 1st, 3rd and 5th generation will be taken from 20 emphysema patients admitted to the bronchoscopic lung volume reduction program in the UMCG.
2. Lung resection material will be obtained from COPD patients and nonCOPD controls, who undergo lung transplantation or lobectomy / pneumectomy because of lung cancer.
3. Lung cancer patients who undergo lobectomy / pneumectomy will be selected on basis of the size and location of the tumor, enabling adequate collection without interfering with routine oncopathology procedures.
4. Adipose tissue (1cm3) will be obtained during the same lung resection procedures described in points 2 and 3.
- Primary outcome1. Succesfull isolation and culturing of mesenchymal stemcells derived from lung tissue.
2. Succesfull isolation and culture of mesenchymal stemcells derived from adipose tissue.
- Secondary outcome1. Analyses of differential MSC function between COPD and control groups through RTPCR, immunohistochemical stainings and Western Blot.
- TimepointsAll tissue will be collected during the planned interventions, with no additional time points planned.
- Trial web site
- status[default]
- CONTACT FOR PUBLIC QUERIESDr. N.H.T. Hacken, ten
- CONTACT for SCIENTIFIC QUERIESDr. N.H.T. Hacken, ten
- Sponsor/Initiator University Medical Center Groningen (UMCG), Department of Pulmonology, University Medical Center Groningen, Department of Pathology, University Medical Center Groningen, Department of Medical Microbiology
- Funding
(Source(s) of Monetary or Material Support)
Longfonds The Netherlands
- Publications
- Brief summaryEmphysema is a prevalent chronic lung disorder associated with chronic inflammation and irreversible alveolar damage. Currently, there is no cure for emphysema. Novel therapeutic strategies are needed, including regenerative approaches using stem cells and bioactive scaffolds. Recent studies indicate that especially the use of mesenchymal stem cells (MSCs) is promising. MSCs produce antiinflammatory factors and display regenerative capacity, constituting a niche for alveolar repair by the production of growth factors and structural proteins. Animal studies indicate that delivery of autologous lungderived MSCs can reduce alveolar damage. Still, the challenge of regenerative medicine in emphysema is considerable. The reparative capacity of MSCs from emphysema patients may be deficient, due to an increased oxidative stress burden and/or dysregulation of lung developmental pathways, as corroborated by preliminary data. Additionally, preliminary data support the notion that there is extensive loss of extracellular matrix (ECM) in emphysema, hampering MSC engraftment and activity. We hypothesize that these abnormalities underlie the defective repair in emphysematous lungs. The use of a bioactive scaffold potentially promotes MSC engraftment, tissue persistence and regenerative capacity, although knowledge on the optimal composition of such a scaffold is limited.

In this obesrvational study we will pay attention to:
Feasibility to derive MSCs from bronchial biopsies, lung tissue resection material, and adipose tissue,
Ability of isolated MSCs to self-renew and differentiate,
Ability of isolated MSCs to expand and express growth factors, anti-inflammatory mediators, cell surface receptors and ECM proteins upon culture,
Improvement of the regenerative capacity of MSCs by the use of effector molecules, e.g. WNT proteins and IL-1R antagonists,
ECM composition of decellularized human lungs at different levels of the bronchoalveolar tree,
Engraftment, cell survival and growth factor expression of MSCs seeded on decellularized human lung slices,
Construction of 3D-scaffolds, mimicking the structure of the normal lung, using different composition of ECM molecules and growth factors,
Bio-scaffold composition that creates an optimal micro-environment that sustains MSC survival and function,
Effects of MSCs on epithelial function, e.g. epithelial barrier function, repair, mitochondrial function and differentiation into alveolosphere-like structures using Matrigel.
- Main changes (audit trail)
- RECORD3-feb-2016 - 20-mrt-2016


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