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Background  The native extracellular matrix (ECM) consists of a highly complex, tissue-specific network of proteins and polysaccharides, which help regulate many cellular functions. Despite the complex nature of the ECM,  in vitro  cell-based studies traditionally assess cell behavior on single ECM component substrates, which do not adequately mimic the  in vivo  extracellular milieu.    Methodology/Principal Findings  We present a simple approach for developing naturally derived ECM coatings for cell culture that provide important tissue-specific cues unlike traditional cell culture coatings, thereby enabling the maturation of committed C2C12 skeletal myoblast progenitors and human embryonic stem cells differentiated into cardiomyocytes. Here we show that natural muscle-specific coatings can (i) be derived from decellularized, solubilized adult porcine muscle, (ii) contain a complex mixture of ECM components including polysaccharides, (iii) adsorb onto tissue culture plastic and (iv) promote cell maturation of committed muscle progenitor and stem cells.    Conclusions  This versatile method can create tissue-specific ECM coatings, which offer a promising platform for cell culture to more closely mimic the mature  in vivo  ECM microenvironment.

Simple and High Yielding Method for Preparing Tissue Specific Extracellular Matrix Coatings for Cell Culture