Stem-Cell Therapy for Esophageal Anastomotic Leakage by Autografting Stromal Cells in Fibrin Scaffold

Abstract

Esophageal anastomotic leakage (EAL) is a devastating complication for esophagectomy but the available therapies are unsatisfactory. Due to the healing effects of mesenchymal stromal cells (MSCs) and supporting capability of fibrin scaffold (FS), we evaluated the efficacy of a stem‐cell therapy for EAL by engrafting adult and autologous MSCs (AAMSCs) in FS and investigated the potential mechanism. Twenty‐one rabbits were assigned to AAMSC/FS group ( n = 12) and control group ( n = 9). After harvested, AAMSCs were identified and then labeled with lenti.GFP. To construct EAL model, a polyethylene tube was indwelled through the anastomosis for 1 week. A total of 2 × 106 AAMSCs in 0.2 ml FS were engrafted onto the EAL for the AAMSC/FS group, whereas FS was injected for control. Magnetic Resonance Imaging (MRI) examination was performed after 5 weeks. Esophageal tissues were harvested for macroscopic, histological analyses, Western blot, and immunohistochemistry at 8 weeks. The animal model of EAL was established successfully. MRI scanning revealed a decreased inflammation reaction in AAMSC/FS group. Accordingly, AAMSC/FS group presented a higher closure rate (83.3% vs. 11.1%, p = .02) and lower infection rate (33.3% vs. 88.9%, p = .02). Histological analyses showed the autografted MSCs resided in the injection site. Furthermore, milder inflammation responses and less collagen deposition were observed in AAMSC/FS group. Western blot and immunohistochemistry studies suggested that the therapeutic effect might be related to the secretions of IL‐10 and MMP‐9. Engrafting AAMSCs in FS could be a promising therapeutic strategy for the treatment of EAL by suppressing inflammation response and alleviating fibrosis progression. stem cells translational medicine 2019;8:548–556

The use of mesenchymal stem cells in animal models for gastrointestinal anastomotic leak: A systematic review

“…Eleven studies utilised allogenic MSCs, and only Sukho et al [21] delivered cultured cells using a xeno-transplant. Eight studies used subcutaneous adipose tissue as the source of MSCs [21][22][23][24][25][26][27]. A further three studies used bone marrow aspirate [22,28,29] and a single study used intrabdominal adipose tissue [30].…”

“…Eight studies used subcutaneous adipose tissue as the source of MSCs [21][22][23][24][25][26][27]. A further three studies used bone marrow aspirate [22,28,29] and a single study used intrabdominal adipose tissue [30]. All cells were cultured to confluence, most commonly at third passage with a median of 2 × 10 6 cells (1 × 10 6 -1 × 10 7 ) applied.…”

Regenerative medicine approaches for the management of respiratory tract fistulas

“…The ideal scaffold should be biocompatible and biodegradable, with a degradation rate similar to the tissue regeneration time. Placement of tissue-engineered graft has been mostly described in preclinical models: for instance, the use of suture filament embedded with adipose tissue-derived MSC has been used to promote fistula healing in a rat model [111]; promotion of esophageal anastomotic leakage healing has been achieved in rabbits by administration of fibrin scaffolds including MSC [112]; synthetic polyurethane electro-spun grafts seeded with autologous MSC have been tested for esophageal tissue remodeling in pigs [113]. To circumvent possible biocompatibility problems, esophagus-like scaffold-free structures embedded with MSC suitable for esophageal repair have been generated by 3D bioprinting and transplanted in rats [114].…”

Utilizing Adipose Tissue-Derived Stem Cell Strategies for Obtaining Regeneration of Respiratory Tract Fistulas-A Systematic Review

“…Placing tissue engineered graft has been detailed maximum in preclinical studies, like the utilization of Adipose tissue attached to suture material or suture filament embedded with adipose tissue obtained MSC's has been utilized to promote entero cutaneous fistulas healing or closure in a rat model [106]. Facilitation of esophageal anastamotic leakage healing has got utilized in rabbits by delivery of fibrin scaffold that includes autografting stromal Cells in MSC's [107]. Similarly electrospun grafts seeded with autologous MSC's have been experimented on in remodelling of the pig esophagus after circumferential resection [108].…”