Cell-Derived Extracellular Matrix for Tissue Engineering and Regenerative Medicine

Abstract

Cell-derived extracellular matrices (CD-ECMs) captured increasing attention since the first studies in the 1980s. The biological resemblance of CD-ECMs to their in vivo counterparts and natural complexity provide them with a prevailing bioactivity. CD-ECMs offer the opportunity to produce microenvironments with costumizable biological and biophysical properties in a controlled setting. As a result, CD-ECMs can improve cellular functions such as stemness or be employed as a platform to study cellular niches in health and disease. Either on their own or integrated with other materials, CD-ECMs can also be utilized as biomaterials to engineer tissues de novo or facilitate endogenous healing and regeneration. This review provides a brief overview over the methodologies used to facilitate CD-ECM deposition and manufacturing. It explores the versatile uses of CD-ECM in fundamental research and therapeutic approaches, while highlighting innovative strategies. Furthermore, current challenges are identified and it is accentuated that advancements in methodologies, as well as innovative interdisciplinary approaches are needed to take CD-ECM-based research to the next level.

Lectin Staining of Microvascular Glycocalyx in Microfluidic Cancer Cell Extravasation Assays

“…The seeding media contained sodium hydroxide neutralized collagen I (collagen I from rat tail in acetic acid, BD354236) at 0.2 mg/mL, the non-specific metalloproteinase inhibitor GM6001 (Millipore CC1010) at a concentration of 0.15 units (U)/mL, and bovine thrombin (Sigma Aldrich T4648-1KU) at a concentration of 0.5 U/mL. Collagen I is helpful to engineer the hydrogel with extracellular matrix components [19]. Collagen I induces motility in endothelial cells for network formation [20].…”

Development of Multilayer Mesenchymal Stem Cell Cell Sheets

“…There are different advantages to using the cell sheet technology. For example, the extracellular matrix and the cell-cell connection are well preserved, increasing the cell adhesion for transplantation and the cell survival, respectively [105]. In addition, it is possible to compile different types of cell sheets to mimic a functional organ, improving then the curative properties of the cell sheet [106].…”

Bioactive Decellularized Extracellular Matrix Derived from 3D Stem Cell Spheroids under Macromolecular Crowding Serves as a Scaffold for Tissue Engineering

“…Typically, tissue-derived dECM has a defined composition, and its bioactivity cannot be customized toward a specific application. [6] Therefore, there is an urgent need of fabricating 3D dECM scaffolds, which are reliably safe and can be easily tailored toward a desired bioactivity that allows to meet the demand for bioactive scaffolds for regenerative medicine.…”

“…ECM derived from cells cultivated in vitro contains abundant and diverse matrix proteins and associated factors and can partially recapitulate the microenvironment of native matrices to serve as a potential alternative to tissue-derived dECM scaffolds. [6,7] In addition, several properties of cell-derived dECM scaffolds can be readily tuned during the cell culture stage, offering additional flexibility and opportunities for customization. [6] The cell-derived dECM scaffolds are typically prepared from the cells of interest (usually adult stem cells or fibroblasts) plated in a conventional culture vessel where they proliferate and deposit ECM for 1-6 weeks.…”

“…[6,7] In addition, several properties of cell-derived dECM scaffolds can be readily tuned during the cell culture stage, offering additional flexibility and opportunities for customization. [6] The cell-derived dECM scaffolds are typically prepared from the cells of interest (usually adult stem cells or fibroblasts) plated in a conventional culture vessel where they proliferate and deposit ECM for 1-6 weeks. [8] However, these 2D culture conditions dramatically differ from native conditions of a 3D tissue.…”