Molecular cross-talk of mouse mesenchymal stem cells with different kinds of liver cells

Abstract

osteoblasts, adipocytes, chondrocytes, tenocytes, and myoblasts, and contribute to the regeneration of a variety of mesenchymal tissues. Adipose tissue represents a rich source of mesenchymal stem cells, and provides an abundant and accessible source of adult stem cells with minimal patient discomfort. Isolation of adipose tissue-derived stem cells (ADSCs) has primarily been achieved with Liberase HI, which is composed of Clostridium histolyticum collagenases I and II and thermolysin. All Liberase preparations contain endotoxin, which is harmful for cell viability. The recombinant production of Liberase enzymes is marred by the instability of collagenase I. The matrix metalloproteinases (MMPs) are a family of enzymes capable of catalyzing the degradation of virtually all ECM components, including collagens, laminin, fibronectin, and elastin. We have explored recombinant MMP cocktails for the efficient isolation of ADSCs, and found one approach (Matrizyme I) that (1) is effective in the isolation of stem cells from adipose tissue, (2) has similar isolation efficiencies as bacterial collagenase, and (3) is stored in an inactive form that can be activated when needed. The use of recombinant MMPs is very significant, because without the highest quality of connective tissue degrading enzymes it is virtually impossible to liberate viable ADSCs with good and stable proliferative capabilities.