1. Locally Transplanted Adipose Stem Cells Reduce Anastomotic Leaks in Ischemic Colorectal Anastomoses: A Rat Model
- Author
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Michael E Kwiatt, Francis R. Spitz, Kimberly M. Linden, Andrew Zheng, Andrew B. Morgan, Jeffrey P. Carpenter, Spencer A. Brown, and Ping Zhang
- Subjects
Gynecology ,medicine.medical_specialty ,Absorbable gelatin sponge ,business.industry ,Rat model ,Gastroenterology ,Adipose tissue ,General Medicine ,Colorectal anastomosis ,Anastomosis ,Subcutaneous fat ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Anastomotic leaks ,Medicine ,030211 gastroenterology & hepatology ,Stem cell ,business - Abstract
Background Anastomotic leakage remains a dreaded complication after colorectal surgery. Stem-cell-based therapies have been shown to increase angiogenesis and cell proliferation. Objective The purpose of this research was to investigate the use of adipose-derived stem cells on the healing of ischemic colonic anastomoses in a rat model. Design This is an animal research study using xenotransplantation. Settings Male Wistar rats (300-400 g, n = 48) were purchased from a licensed breeder. Patients Adipose stem cells were isolated from the subcutaneous fat of healthy human donors. Interventions The rats underwent laparotomy with creation of an ischemic colorectal anastomosis created by ligation of mesenteric vessels. The animals were divided into 3 groups: control group with an ischemic anastomosis, vehicle-only group in which the ischemic anastomosis was treated with an absorbable gelatin sponge, and a treatment group in which the ischemic anastomosis was treated with an absorbable gelatin sponge plus adipose stem cells. Animals were killed at postoperative days 3 and 7. Main outcome measures Anastomotic leakage was defined as the finding of feculent peritonitis or perianastomotic abscess on necropsy. Rat mRNA expression was measured using real-time polymerase chain reaction. Results Adipose-derived stem cells significantly decreased anastomotic leakage when compared with control at both postoperative days 3 (25.0% vs 87.5%; p = 0.02) and 7 (25.0% vs 87.5%; p = 0.02). The use of an absorbable gelatin sponge alone had no effect on anastomotic leakage when compared with control and postoperative days 3 or 7. We found that stem cell-treated animals had a 5.9-fold and 7.4-fold increase in the expression of vascular endothelial growth factor when compared with control at 3 and 7 days; however, this difference was not statistically significant when compared with the absorbable gelatin sponge group. Limitations This is a preclinical animal research study using xenotransplantation of cultured stem cells. Conclusions Locally transplanted adipose stem cells enhance the healing of ischemic colorectal anastomoses and may be a novel strategy for reducing the risk of anastomotic leakage in colorectal surgery. See Video Abstract at http://links.lww.com/DCR/B203. EL TRANSPLANTE LOCAL DE CELULAS MADRE ADIPOSAS REDUCE LA FUGA ANASTOMOTICA EN LAS SUTURAS COLORRECTALES ISQUEMICAS: MODELO EN RATAS: Las fugas anastomoticas son una complicacion pusilanime despues de toda cirugia colorrectal. Se ha demostrado que el tratamiento con celulas madre aumenta la angiogenesis y la proliferacion celular.Investigar el uso de celulas madre derivadas de tejido adiposo en la cicatrizacion de una anastomosis colonica isquemica basada en ratas como modelo.Estudio de investigacion en animales utilizando xenotrasplantes.Adquisicion de tipicas ratas de laboratorio raza Wistar, todas machos (300-400 g, n = 48) de un criadero autorizado.Aislamiento de celulas madre de tipo adiposo del tejido celular subcutaneo en donantes humanos sanos.Las ratas se sometieron a laparotomia con la creacion de una anastomosis colorrectal isquemica obtenida mediante ligadura controlada de los vasos mesentericos correspondientes. Los animales se dividieron en tres grupos: grupo de control con anastomosis isquemica, grupo de vehiculo unico en el que la anastomosis isquemica se trato con una esponja de gelatina absorbible, y un grupo de tratamiento en el que la anastomosis isquemica se trato con una esponja de gelatina absorbible asociada a un vastago adiposo de celulas madre. Los animales fueron sacrificados el POD3 y el POD7.La fuga anastomotica fue definida como el hallazgo de peritonitis fecaloidea o absceso perianastomotico a la necropsia. La expresion de RNAm de las ratas se midio usando PCR en tiempo real.Las celulas madre derivadas de tejido adiposo disminuyeron significativamente la fuga anastomotica en comparacion con el grupo control tanto en el POD3 (25% frente a 87.5%, p = 0.02) como en el POD7 (25% frente a 87.5%, p = 0.02). El uso de una esponja de gelatina absorbible sola, no tuvo efecto sobre la fuga anastomotica en comparacion con los controles el POD3 o el POD7. Descubrimos que los animales tratados con celulas madre adiposas tenian un aumento de 5,9 y 7,4 veces en la expresion de VEGF en comparacion con el control a los 3 y 7 dias, respectivamente; sin embargo, esta diferencia no fue estadisticamente significativa en comparacion con el grupo de esponja de gelatina absorbible.Este es un estudio preclinico de investigacion en animales que utiliza xenotrasplantes de celulas madre adiposas cultivadas.Las celulas madre de tipo adiposo trasplantadas localmente mejoran la cicatrisacion en casos de anastomosis colorrectales isquemicas, y podrian convertirse en una nueva estrategia para reducir el riesgo de fugas anastomoticas en casos de cirugia colorrectal. Consulte Video Resumen en http://links.lww.com/DCR/B203. (Traduccion-Dr Xavier Delgadillo).
- Published
- 2020
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