A novel chemotactic factor derived from the extracellular matrix protein decorin recruits mesenchymal stromal cells in vitro and in vivo.

Soft tissue is composed of cells surrounded by an extracellular matrix that is made up of a diverse array of intricately organized proteins. These distinct components work in concert to maintain homeostasis and respond to tissue damage. During tissue repair, extracellular matrix proteins and their degradation products are known to influence physiological processes such as angiogenesis and inflammation. In this study we developed a discovery platform using a decellularized extracellular matrix biomaterial to identify new chemotrophic factors derived from the extracellular matrix. An in vitro culture of RAW.264 macrophage cells with the biomaterial ovine forestomach matrix led to the identification of a novel ~12 kDa chemotactic factor, termed 'MayDay', derived from the N-terminal 31-188 sequence of decorin. The recombinant MayDay protein was shown to be a chemotactic agent for mesenchymal stromal cells in vitro and in vivo. We hypothesize that the macrophage-induced cleavage of decorin, via MMP-12, leads to the release of the chemotactic molecule MayDay, that in turn recruits cells to the site of damaged tissue.
Competing Interests: BCHM, RWFV and SGD are paid employees of Aroa Biosurgery Limited (Auckland, New Zealand). JS is a paid employee of Charles River (Freiburg, Germany). DGD and CHM are paid employees of Victoria University (Wellington, New Zealand). BCHM, SGD and CHM are shareholders of Aroa Biosurgery Limited. BCHM, SGD and DJD are listed as inventors on provisional patent U.S. Provisional Application No. 62/857,900, owned by Aroa Biosurgery Limited. BCHM is listed as inventor on patent US8415159B2, owned by Aroa Biosurgery Limited. Ovine forestomach matrix is manufactured by Aroa Biosurgery Limited and is available as commercial medical devices under the tradenames Endoform® Natural, Endoform® Antimicrobial, Myriad™, and Ovitex® distributed international by Aroa Biosurgery Limited This does not alter the authors adherence to PLOS ONE policies on sharing data and materials.