Future prospects for tissue engineered lung transplantation: decellularization and recellularization-based whole lung regeneration

Abstract

The shortage of donor lungs for transplantation causes a significant number of patient deaths. The availability of laboratory engineered, functional organs would be a major advance in meeting the demand for organs for transplantation. The accumulation of information on biological scaffolds and an increased understanding of stem/progenitor cell behavior has led to the idea of generating transplantable organs by decellularizing an organ and recellularizing using appropriate cells. Recellularized solid organs can perform organ-specific functions for short periods of time, which indicates the potential for the clinical use of engineered solid organs in the future. The present review provides an overview of progress and recent knowledge about decellularization and recellularization-based approaches for generating tissue engineered lungs. Methods to improve decellularization, maturation of recellularized lung, candidate species for transplantation and future prospects of lung bioengineering are also discussed.

Keywords: decellularization; extracellular matrix; induced pluripotent stem cells; lung transplantation; recellularization; stem/progenitor cells.

Figure 1. Schematic of decellularization and recellularization based whole lung regeneration for transplantation. Harvested human or animal lungs are decellularized by detergents such as SDS, CHAPS, or Triton-X. The decellularized lung is recellularized by the recipient’s own stem/progenitor cells or iPSCs.

Figure 2. (A) Comparison of Collagen, GAG, and DNA content in untreated control lung vs. decellularized lung. Asterisk indicates a significant difference between the groups (*; P < 0.05, **; P < 0.005,). Data are expressed as mean values ±SD, n = 5. (B) Histological and immunohistochemical comparison of the ECM in untreated control lung vs. decellularized lung. Scale bar = 100 µm

Figure 3. Possible approaches for recellularization and maturation of decellularized lung. Harvested stem cells can be matured and differentiated in vitro or left in the progenitor cell state using trophic factors and re-seeded into decellularized lung scaffolds. Mediators can then be used to support maturation, followed by bioreactor culture using intermittent mechanical stretch to simulate fetal breathing. Length and extent of organ maturation ex vivo can vary.