Role of inflammation in tissue repair
- Inflammation and chondrogenesis
Role of inflammation in chondrogenesis - MSCs and mature chondrocytes
Aim: To investigate the effect of inflammation on chondrogenesis in mesenchymal stem cells (MSCs) from equine bone marrow, adipose tissue, and synovial fluid.
Short description: General consensus is that inflammation is detrimental to tissue generation and regeneration. In this study we challenge this statement and suggest that inflammation may play a positive role in cartilage tissue formation.
The hypothesis of this study is that inflammation supports chondrogenesis in equine MSCs and mature chondrocytes. We are also investigating whether different MSCs respond equally to inflammation.
Main investigator: Lise C. Berg
Preliminary findings - MSCs: Equine MSCs from bone marrow, adipose tissue, and synovial fluid were differentiated towards chondrogenesis using TGF-beta3 in monolayer cultures (12 days) and pellet cultures (30 days). Mature chondrocytes were cultured in chondrogenic media.
Inflammation was induced using interleukin-1 beta or serum amyloid a in a high dose or low dose in order to mimic acute high grade inflammation or more chronic low grade inflammation. In pellet cultures high grade inflammation was suspended on day 12. All cultures showed chondrogenesis with safranin O staining. Control cultures without inflammation showed strong expression of cartilage marker genes. Inflammation had varying effect on chondrogenesis depending on stimuli and on cell type.
Preliminary findings - mature chondrocytes: Equine articular chondrocytes were cultured in chondrogenic conditions in monolayer cultures (12 days) and pellet cultures (30 days). Inflammation was induced using interleukin-1 beta or serum amyloid a in a high dose or low dose in order to mimic acute high grade inflammation or more chronic low grade inflammation. In pellet cultures high grade inflammation was suspended on day 12. All cultures showed deposition of cartilage-specific extracellular matrix with safranin O staining with more matrix deposited in cultures treated with high dose - short duration inflammation. Control cultures without inflammation showed expression of cartilage marker genes similar to low dose - long duration inflammation.
Funding: The MSC part of this project was funded in part by Hesteafgiftsfonden, http://www.hesteafgiftsfonden.dk
Publication:
L. C. Berg, P. D. Thomsen (2012) Is chondrogenic differentiation affected equally by inflammation in different equine MSCs? Abstract in proceedings from NAVRMA (North American Veterinary Regenerative Medicine Association) annual meeting 2012, Savannah, USA.