Circumferential Esophageal Replacement by a Tissue-engineered Substitute Using Mesenchymal Stem Cells

Abstract

Tissue engineering appears promising as an alternative technique for esophageal replacement. Mesenchymal stem cells (MSCs) could be of interest for esophageal regeneration. Evaluation of the ability of an acellular matrix seeded with autologous MSCs to promote tissue remodeling toward an esophageal phenotype after circumferential replacement of the esophagus in a mini pig model. A 3 cm long circumferential replacement of the abdominal esophagus was performed with an MSC-seeded matrix (MSC group, n = 10) versus a matrix alone (control group, n = 10), which has previously been matured into the great omentum. The graft area was covered with an esophageal removable stent. A comparative histological analysis of the graft area after animals were euthanized sequentially is the primary outcome of the study. Histological findings after maturation, overall animal survival, and postoperative morbidity were also compared between groups. At postoperative day 45 (POD 45), a mature squamous epithelium covering the entire surface of the graft area was observed in all the MSC group specimens but in none of the control group before POD 95. Starting at POD 45, desmin positive cells were seen in the graft area in the MSC group but never in the control group. There were no differences between groups in the incidence of surgical complications and postoperative death. In this model, MSCs accelerate the mature re-epitheliazation and early initiation of muscle cell colonization. Further studies will focus on the use of cell tracking tools in order to analyze the becoming of these cells and the mechanisms involved in this tissue regeneration.

Successful muscle regeneration by a homologous microperforated scaffold seeded with autologous mesenchymal stromal cells in a porcine esophageal substitution model

“…31,[37][38][39][40] When used in combination with acellular matrix for esophageal replacement strategies, MSCs were shown to promote re-epithelialization, to accelerate muscle colonization and regeneration, and to exert an anti-inflammatory role. [41][42][43][44] In this study, we describe a preliminary approach to the esophageal substitution based on a homologous decellularized scaffold 45,46 seeded with autologous bone-marrow-derived MSCs (BM-MSCs). In order to enhance cell seeding throughout the scaffold, this was microperforated by needles using Quantum Molecular Resonance ® (QMR).…”

In Vitro Regeneration of Decellularized Pig Esophagus Using Human Amniotic Stem Cells

“…Previous reports on regeneration of epithelial and muscular regions of esophagus in small and large animal models show the possibility of in vivo regeneration of partially recellularized natural or artificial scaffolds. [22][23][24] This tissue-specific differentiation of cell types in recellularized tissue suggest that engineered esophagus would be suitable for future in vivo applications.…”

Esophageal tissue engineering: from bench to bedside

“…demonstrated that bone marrow MSCs on an SIS scaffold (Surgisis®; Cook Biotech Inc.) can promote re‐epithelialization, revascularization, and muscular regeneration . In minipigs, it has also been demonstrated that after circumferential replacement of the esophagus, the presence of autologous MSCs accelerated mature re‐epithelialization and the initiation of muscle cell colonization . Future studies characterizing the secretome of these MSCs may reveal the mechanism underlying tissue repair by MSC‐seeded matrices.…”