Abstract
Porcine extracellular matrix (pECM)-derived hydrogels were introduced, in recent years, aiming to benefit the pECM’s microstructure and bioactivity, while controlling the biomaterial’s physical and mechanical properties. The use of pECM from different tissues, however, offers tissue-specific features that can better serve different applications. In this study, pECM hydrogels derived from cardiac, artery, pancreas, and adipose tissues were compared in terms of composition, structure, and mechanical properties. While major similarities were demonstrated between all the pECM hydrogels, their distinctive attributes were also identified, and their substantial effects on cell-ECM interactions were revealed. Furthermore, through comprehensive protein and gene expression analyses, we show, for the first time, that each pECM hydrogel supports the spontaneous differentiation of induced pluripotent stem cells towards the resident cells of its origin tissue. These findings imply that the origin of ECM should be carefully considered when designing a biomedical platform, to achieve a maximal bioactive impact.
Highlights
Sci. 2021, 22, 11624. https://doi.org/Accumulating knowledge on the extracellular matrix (ECM) interactions with the tissue and its cellular components has revealed the major role of tissue ECM in regulating cellular processes in health and disease, as well as in governing cell behavior and fate [1,2]
To further investigate whether a tissue-specific microenvironment is provided to resident cells by the Porcine extracellular matrix (pECM) hydrogels, we addressed the effect of the different hydrogels on stem cell differentiation
The spontaneous differentiation of hiPSCs cultured on pECM hydrogels derived from different tissues was initially addressed using immunostaining of markers specific to cells residing in the tissues of origin
Summary
Accumulating knowledge on the extracellular matrix (ECM) interactions with the tissue and its cellular components has revealed the major role of tissue ECM in regulating cellular processes in health and disease, as well as in governing cell behavior and fate [1,2]. The tissue ECM consists of two main classes of macromolecules: fibrous proteins, including collagen and elastin; and glycoproteins, including proteoglycans, fibronectin, and laminin [4,5,6] This combination of macromolecules generates a fibrous microstructure that grants the tissues the mechanical and physical properties needed for their function. We hypothesized that the tissue-specific characteristics of each ECM will significantly affect its function as a biomaterial when processed into a hydrogel for different biomedical applications, both in terms of the structural and mechanical properties of the hydrogel and in terms of its interplay with the residing cells, i.e., its ability to support their viability and function as well as to direct stem cells differentiation toward the tissue from which the ECM was originated. ECM (pECM) hydrogels derived from different tissues, in terms of composition, structure, and mechanical properties and studied their effects on cell culture and differentiation through total RNA sequencing analyses
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