Human Adipose Derived Stem Cells Enhance Healing in a Rat Model of Esophageal Injury with Stent

Background: Mesenchymal stem cells have been proven to promote cellular recruitment and remodeling during healing. Considering challenges encountered in the healing process of esophageal injury, we sought to evaluate the effect of human adipose derived stem cells (hASC) on esophageal injury with stent and to assess the feasibility of submucosal hASC injection as a mechanism of delivery.Methods: An intrabdominal esophagotomy was created in rodents with placement of an expandable fully covered metal esophageal stent. A submucosal injection of 2 x 10(6) hASC was delivered in experimental animals. Animals were sacrificed on postoperative day 3 (POD3) or 7 (POD7). Macroscopic, immunohistochemical and immunofluorescence analyses were conducted to assess for markers of healing and viability of transplanted cells.Results: hASC were identified within submucosal and muscular layers with proliferation demonstrated in respective areas on anti-Ki67 stained sections. Lower adhesion and abscess scores were observed in hASC specimens without significant statistical difference. Prevalence of submucosal collagen was increased in samples treated with hASC compared to control, with abundant collagen deposition demonstrated within the POD7 group. Granulation tissue at the site of esophageal injury was more prominent in tissue sections treated with hASC compared to control, with significantly higher density at POD3 (control 1.94 versus hASC 2.83, P < 0.01).Conclusions: Presence of hASC at the site of an esophageal injury may enhance wound healing predominantly through increased granulation and decreased inflammation in con-junction with esophageal stent placement. Targeted submucosal injection at the time of esophageal stent placement is an effective delivery method of hASC therapy. (C) 2021 Elsevier Inc. All rights reserved.