Tissue and organ decellularization in regenerative medicine

Abstract

The advancement and improvement in decellularization methods can be attributed to the increasing demand for tissues and organs for transplantation. Decellularized tissues and organs, which are free of cells and genetic materials while retaining the complex ultrastructure of the extracellular matrix (ECM), can serve as scaffolds to subsequently embed cells for transplantation. They have the potential to mimic the native physiology of the targeted anatomic site. ECM from different tissues and organs harvested from various sources have been applied. Many techniques are currently involved in the decellularization process, which come along with their own advantages and disadvantages. This review focuses on recent developments in decellularization methods, the importance and nature of detergents used for decellularization, as well as on the role of the ECM either as merely a physical support or as a scaffold in retaining and providing cues for cell survival, differentiation and homeostasis. In addition, application, status, and perspectives on commercialization of bioproducts derived from decellularized tissues and organs are addressed. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1494–1505, 2018

Sequential adaptation of perfusion and transport conditions significantly improves vascular construct recellularization and biomechanics

“…* indicates significant differences between SF30 and DF30 (p < .05) (e) The metabolic activity, however, was similar for both pressure conditions. * indicates significant differences between SF-Hypo45 and SF-Normo45 (p < .05) decellularization techniques have been developed that allow for removal of immunogenic cellular materials while preserving the nonimmunogenic ECM architecture and bioactive factors (Damodaran & Vermette, 2018;Gilpin & Yang, 2017;Porzionato et al, 2018). Scaffolds extracted from xenogeneic organisms and also from human origin have thus emerged and have become a therapeutic actuality opening up the opportunity for full allogeneic graft development (M. C. Moore et al, 2017).…”

Processed Tissue–Derived Extracellular Matrices: Tailored Platforms Empowering Diverse Therapeutic Applications

“…Triton X‐100 is considered to be a milder agent due to its nonionic nature and could thereby be an appropriate candidate for the decellularization of relatively fragile tissues such as the pericardium and the pancreas . Triton X‐100 has also been used in combination with SDS to assist its wash during the procedure, which resulted in efficient cell removal and ECM preservation . Zwitterionic detergents such as 3‐[(3‐cholamidopropyl)dimethylammonio]‐1‐propanesulfonate (CHAPS) exhibit nondenaturing properties and were shown highly beneficial in maintaining ECM integrity of thin tissues like the lungs .…”

Emerging technologies in organ preservation, tissue engineering and regenerative medicine: a blessing or curse for transplantation?

“…During freezing and thawing, osmotic changes and ice crystal formation promotes cell lysis while only inducing minor changes in the mechanical properties of the ECM . In a second step, different detergents are used to extract all natural cellular material from the organ, preferably without damaging ECM components either by immersion/agitation, vascular perfusion, via pressure gradients, or by using supercritical fluids . Sufficient decellularization is essential to reduce immunogenicity of scaffolds, but, in most instances, a small amount of cell components (i.e.…”

“…Despite these promising reports, recellularization of whole organ scaffolds remains challenging and further studies and refinements of the currently applied protocols are needed to make this field clinically applicable. Ongoing hurdles include the precise positioning of seeded cell types inside the organ or tissue scaffold, providing adequate oxygen and nutrient supply, enabling metabolic waste product removal and minimization of thromboembolic events during recellularization . As well, there is currently a degree of difficulty in achieving adequate lymphatic drainage and vascularization of recellularized organs, something that needs to be addressed to optimize functional outcomes .…”

“…Nevertheless, other types of scaffolds and ECM generated via decellularization methods are already commercially available. Xenogeneic decellularized scaffolds, for instance, are regularly used for patients with wound‐healing defects .…”