Stem cell-derived extracellular matrix in regenerative medicine

by Alexey Bersenev on May 25, 2012  Extracellular matrix (ECM) is a powerful and very promising biological product for regenerative medicine. Recently, a few research groups, have proposed to use stem cell-derived ECM. Let’s look at some of these studies.In 2008, Wataru Ando proposed to use a methodology of scaffold-free tissue engineering, based on stem cell-derived ECM. The authors created a construct including monolayer of cultured human synovial mesenchymal stem cells (MSC) with abundant ECM.One of the first attempts to make stem cell-derived ECM was taken in 2009. Researchers used human unfractioned bone marrow mononuclear cells to produce ECM in vitro. The authors compared human mesenchymal stromal cell (MSC) culture properties on naturally produced ECM versus plastic: The results showed that MSCs expanded on the ECM for multiple passages still retained the same capacity for skeletogenesis. In contrast, the bone formation capacity of cells expanded on plastic was dramatically diminished after 6–7 passages. These findings suggest that the marrow stromal cell-derived ECM is a promising matrix for expanding large-scale highly functional MSCs for eventual use in stem cell-based therapy.Very interesting study, assessing influence of young versus old bone marrow-derived ECM on aged MSC, was published last year: We concluded that aging negatively affects the formation of an ECM that normally preserves MSC function, and aged MSCs can be rejuvenated by culture on a young-ECM.Rocky Tuan’s group studied influence of human MSC-derived ECM on biological properties of these cells. They significantly improved the methodology: Native ECM produced by human MSC in vitro was extracted in urea, and the residual pellet was further processed with pepsin digestion (denoted as U-MECM and HP-MECM, respectively). The MECM products were then coated as a substrate on standard tissue culture plastic, and the behavior of MSCs seeded on the coated surfaces was studied. Our results showed that U-MECM coating dramatically accelerated MSC proliferation, attachment, spread, migration and multi-lineage differentiation (i.e., osteogenesis and adipogenesis), compared to collagen type I and HP-MECM coating.Carl Gregory’s group used a sophisticated approach in a model of bone regeneration. They loaded human MSC-derived ECM with MSC treated by small molecule – osteogenesis inductor: … we demonstrate that the osteo-repair capacity of hMSCs can be substantially augmented by treatment with an inhibitor of peroxisome proliferator–activated receptor γ, but efficacy is confined to the rapid osteogenic phase. Upon entry into the bone-remodeling phase, hMSC retention signals are lost, resulting in truncation of healing. To solve this limitation, we prepared a scaffold consisting of hMSC-derived extracellular matrix (ECM) containing the necessary biomolecules for extended site-specific hMSC retention.So, the current trend in scaffold-free tissue engineering is using cell-derived extracellular matrix. The most work in this direction was done on mesenchymal stromal cells and fibroblasts. Potential superiority of human MSC-derived ECM compared to other methods was demonstrated in skeletal tissue regeneration models. Yet another potentially promising approach is using autologous stem cell-derived ECM in regenerative medicine.