**2.1. Mesenchymal stem/stromal cells**

Adult mesenchymal stem/stromal cells (MSCs) are found in all postnatal organs and tissues, and they play important functions in tissue injury repair and general homeostasis [15]. These cells are one of the principal adult stem cells and the most promising tool for regenerative medicine because of their sustained proliferative capacity and their multipotent differentiation potential [15–17].

### *2.1.1. Fibroblasts*

**ASC** Adipose tissue-derived stem cells

342 Composition and Function of the Extracellular Matrix in the Human Body

**HMVEC** Human microvascular endothelial cell **HUVEC** Human umbilical vein endothelial cell

**EC** Endothelial cells **ECM** Extracellular matrix **HA** Hyaluronic acid

**L–Arg** L–arginine

**NG2** Neuron glial-2

**2D** Two-dimensional **3D** Three-dimensional

**1.1. ECM deposition and assembly**

**1. Introduction**

**PLGA** Poly-lactic-co-glycolic acid

**SVF** Adipose stromal vascular fraction **TGF-β** Transforming growth factor-beta **TIMP** Tissue inhibitors of metalloproteinases **VEGF** Vascular endothelial growth factor

The extracellular matrix (ECM) is present within all tissues and organs. It constitutes the noncellular microenvironment around the cells that plays an important role in modulating their behavior and functions [1]. This elaborated milieu is very dynamic and extremely adaptable [2– 4]. ECM is composed of several components that include proteoglycans, as well as collagen proteins and noncollagenous glycoproteins. Each component has several subcategories of

The homeostasis of epithelial tissues depends on a dynamic interaction of the stroma compo‐ nents, such as fibroblasts, adipocytes, and nonactivated immune players [6]. In fact, fibroblasts were reported to secrete and organize type I and type III collagens, elastin, fibronectin, tenascin, and a repertoire of proteoglycans (hyaluronic acid (HA) and decorin), that maintains interstitial ECM integrity [7]. The ECM is constantly remodeled to allow the healthy tissue to

molecules that influence the ECM physical and biochemical properties [5].

**LOX** Lysyl oxidase enzymes **LOXL** Lysyl oxidase homologues **LPA** Lysophosphatidic acid **MMP** Matrix metalloproteinases **MSC** Mesenchymal stem/stromal cells

> Fibroblasts are nonterminally differentiated mesenchymal cells derived from the embryonic mesoderm [18]. They are found in the connective tissue, a tissue that supports the whole body. Fibroblasts are spread in the ECM containing fibrous proteins and gel-like substances. In fact, fibroblasts produce the ECM proteins, such as fibrous collagen and elastin, as well as adhesive proteins such as laminin and fibronectin. Fibroblasts are also the major source of glycosami‐ noglycans (hyaluronan and glycoproteins) [19]. Interconnecting meshworks of extracellular protein fibers and connector proteins provide the architectural tissue structure. Moreover, this milieu forms the connections needed for cellular migration of fibroblasts, immune cells, and endothelial cells (ECs) during angiogenesis [19].

> Most tissues are composed of a simple or multiple layers of epithelial cells that exhibit an apical–basal polarization. The basal part is in contact with the basement membrane, whereas the apical side is oriented toward the fluid-filled lumen [20]. Fibroblasts form a basement membrane, composed of a layer of basal lamina and a layer of reticular lamina. This basement membrane serves essentially as a structural scaffold that maintains the dynamics of a threedimensional (3D) engineered tissue. It is also critical for tissue regeneration in wound healing and acts as a cell barrier. The basement membrane acts as a cell barrier by segregating epithelial cells from endothelial cells (ECs), thus preventing tumor invasion or metastasis.
