## 1 Extracellular Matrix (ECM) and Secreted Protein Acidic and Rich in Cysteine (SPARC)  
The increasing number of pathologies involving structural or functional abnormalities, combined with the lack of organ donors, has made developing novel approaches in regenerative medicine a necessity. Recent advances in regenerative medicine have brought a lot of hope for tissue engineering, as shown by clinical trials that use stem cells (both somatic and embryonic and even adipose-derived stem cells) in therapeutic applications [1; 2; 3]. Within the context of regenerative medicine, the ECM is implicated in a variety of processes that include cellular repair and regeneration, remodeling [4], and intercellular communication [5] (Figure 1). Therefore, ECM products, including hydrogels [5], have been used or suggested in clinical practice [6; 7]. Such applications derive from the structural and functional properties of the ECM and its associated proteins. Thus, further understanding these properties could expand the applications in regenerative medicine as well as in fields such as pharmacology and in vitro researches. ECM is a three-dimensional network surrounding cells, and is made of different macromolecules, including collagens, elastins, proteoglycans/glycosaminoglycans, laminins, and fibronectins [5, 8]. It governs a variety of biological functions such as cellular differentiation, growth, survival, migration, homeostasis, and morphogenesis [8]. ECM remodeling through its components is crucial in both physiology and pathology [9, 10, 11]. Such remodeling is controlled by epigenetics through the dynamic cellular environment (pH, cytokines, etc. [12]) that induces gene expression modulations [9] towards a modified proteomic profile required for remodeling. On the other hand, the proteins associated with the ECM structurally and functionally complete the molecular network surrounding the cells and governing tissue properties. Herein, we mention the SPARC that represents an example of an ECM-associated protein expressed, mainly when tissues change [13, 14], indicating its particular importance during tissue remodeling and suggesting its close interaction with the ECM during such a process. SPARC (also known as BM-40 or osteonectin) is a glycoprotein with a molecular weight of 32 kDa [15] encoded by a highly conserved single gene [16], which reflects the evolutionary importance of this gene. It has a single polypeptide chain [17], and its human-matured version has 286 amino acid residues [18]. This glycoprotein is made of three domains (N-terminal domain, C-terminal domain, and a domain characterized by a follistatin-like domain) [19]. The three domains provide SPARC with its biophysical and biochemical properties such as Ca\({}^{2+}\)-binding, protease inhibitor, and collagen binding [19]. These properties allow SPARC to bind to both collagen and hydroxyapatite [13]. This binding ability is illustrated by studies showing that collagen I and SPARC are both reduced by valpro treatment in cultured bone cells [20], the implication of SPARC in stromal mineralization, as well as the adhesion of both osteoblasts and platelets to the ECM [21]. In fact, SPARC was first discovered in bones [18] and shown to be highly important in osteogenesis [17]. It is also the most expressed in the bone compared to the other noncollagenous polypeptides [22]. SPARC was initially  
Figure 1: Example of extracellular matrix (ECM) implications. The extracellular matrix is involved in a variety of biological functions, mainly but not only during tissue development under physiological and pathological conditions. named osteonectin following its discovery in bones, and was even thought to be bone-specific [13; 23] before it was shown to be expressed in most tissues. Beyond the structural implications of SPARC and ECM, it remains important to clarify their metabolic and homeostatic properties under different circumstances.