Transferable Matrixes Produced from Decellularized Extracellular Matrix Promote Proliferation and Osteogenic Differentiation of Mesenchymal Stem Cells and Facilitate Scale-Up.

Abstract

Decellularized extracellular matrixes (dECM) derived from mesenchymal stem cell (MSC) cultures have recently emerged as cell culture substrates that improve the proliferation, differentiation, and maintenance of MSC phenotype during ex vivo expansion. These biomaterials have considerable potential in the fields of stem cell biology, tissue engineering, and regenerative medicine. Processing the dECMs into concentrated solutions of biomolecules that enable the useful properties of the native dECM to be transferred to a new surface via a simple adsorption step would greatly increase the usefulness and impact of this technology. The development of such solutions, hereafter referred to as transferable matrixes, is the focus of this article. In this work, we produced transferable matrixes from dECM derived from two human placental MSC cell lines (DMSC23 and CMSC29) using pepsin digestion (P-ECM), urea extraction (U-ECM), and mechanical homogenization in acetic acid (AA-ECM). Native dECMs improved primary DMSC proliferation as well as osteogenic and adipogenic differentiation, compared with traditional expansion procedures. Interestingly, tissue culture plastic coated with P-ECM was able to replicate the proliferative effects of native dECM, while U-ECM was able to replicate osteogenic differentiation. These data illustrate the feasibility of producing dECM-derived transferable matrixes that replicate key features of the native matrixes and show that different processing techniques produce transferable matrixes with varying bioactivities. Additionally, these transferable matrixes are able to coat 1.3-5.2 times the surface area covered by the native dECM, facilitating scale-up of this technology.