Role of the Extracellular Matrix in Whole Organ Engineering

Abstract

End-stage organ failure is a devastating problem with limited therapeutic options. The definitive treatment is orthotropic transplantation, however, there exists a severe shortage of viable donor organs, and this shortage is worsening with an aging demographic and as the number of new cases of organ failure increases. Patients fortunate enough to receive a transplant are required to receive immunosuppressive therapies and can face transplant rejection. The emerging concept of organ engineering may offer a new hope for these patients. Researchers in the field of regenerative medicine and tissue engineering are using three-dimensional whole organ scaffolds composed of allogeneic or xenogeneic extracellular matrix (ECM) for engineering functional tissue suitable for transplantation. Perfusion decellularization is an approach that generates native ECM scaffolds with intact 3D anatomical architecture and vasculature. Decellularized organs provide the ideal transplantable scaffold with all the necessary microstructure and extracellular cues for cell attachment, differentiation, vascularization, and function. The present manuscript will review the role of the ECM in normal development, the concept of ECM tissue specificity, and the effect of processing methods on eventual clinical outcomes. An overview of existing challenges and future directions will also be discussed.

Cardiac Extracellular Matrix Scaffold Generated Using Sarcomeric Disassembly and Antigen Removal

“…23 Unlike current patch materials, cardiac Extracellular Matrix (cECM) of xenogeneic tissues possesses appropriate matrix architecture, biochemical composition and mechanical properties, which provides a potentially ideal environment for cell differentiation and orientation to occur. 7 However, the major obstacle to a xenogeneic cECM scaffold approach is that tissue antigenicity must be abolished, or at least significantly ameliorated, to avoid a destructive immune response following implantation in an immunocompetent recipient. 2 Removal of antigenicity, while retaining structure/function relationships is therefore essential for production of an ideal xenogeneic cECM scaffold.…”

“…2 Removal of antigenicity, while retaining structure/function relationships is therefore essential for production of an ideal xenogeneic cECM scaffold. 7 In the field of myocardial tissue engineering, several decellularization methodologies have been tested, including hypotonic solutions, enzymatic treatments, and detergents in various iterations. 5 However, with only a few exceptions, most groups continue using denaturing detergents, such as sodium dodecyl sulfate (SDS), as their main active agent.…”

Tendon-Derived Extracellular Matrix Enhances Transforming Growth Factor-β3-Induced Tenogenic Differentiation of Human Adipose-Derived Stem Cells

“…While the ECM of most tissues share highly conserved structural proteins (e.g., collagen, proteoglycans), it is the unique biophysical arrangement of these proteins and the highly orchestrated deposition and presentation of soluble cues that serve to promote and maintain a particular cell phenotype. 31,32 Tendon is rich in ECM components, and many of the tendon ECM proteins have been found to play important roles in tendon differentiation and organization. [33][34][35] As proof, tendon-derived stem/progenitor cells (TSPCs) seeded on decellularized tendon/ligament ECM demonstrated improved proliferation and tendon cell phenotype.…”

Artificial Ovary

“…This concept involves decellularization of allogeneic or xenogeneic homologous tissue or organ followed by recellularization of the resultant 3D scaffold with autologous cells [44]. Threedimensional decellularized tissue consists exclusively of the component molecules of ECM, ideally preserved in their native ultrastructural architecture.…”