Oral Communications 3 / Clinical Cases 1
13.234 - Mesenchymal Stromal Cells promote bowel regeneration after intestinal transplantation: myth to mucosa
Presenter: Anil, Vaidya, , United Kingdom
Authors: Carlo D.L. Ceresa1, Francesco Dazzi2, Roger N. Ramcharan1, Srikanth Reddy1, Eve Fryer3, Stephen B. Marley2, Fang J. Lee1, Sanjay Sinha1, Peter J. Friend1, Anil Vaidya1
Mesenchymal Stromal Cells promote bowel regeneration after intestinal transplantation: myth to mucosa
Carlo D.L. Ceresa1, Francesco Dazzi2, Roger N. Ramcharan1, Srikanth Reddy1, Eve Fryer3, Stephen B. Marley2, Fang J. Lee1, Sanjay Sinha1, Peter J. Friend1, Anil Vaidya1
1The Oxford Transplant Centre, Churchill Hospital, Oxford, United Kingdom; 2Department of Medicine, Imperial College , London, United Kingdom; 3Department of Cellular Pathology, John Radcliffe Hospital, Oxford, United Kingdom
Mesenchymal stromal cells (MSCs) are a heterogeneous group of cells that have the ability to differentiate to many mesodermal lineages . They possess the dual properties of tissue repair and immunomodulation .
We report the first case of use of MSCs to promote mucosal regeneration in an isolated intestinal transplant recipient who had significant bowel dysfunction following Candida and Noroviral infection.
Fresh MSCs were obtained from a bone marrow donor and one-million cells/kg were infused via a central vein over a period of 15 minutes. Clinical parameters including stoma output and serum citrulline levels were recorded pre- and post- administration of MSCs. Endoscopic imaging of the transplant graft was performed before and after MSC transplantation and histological findings were compared.
Prior to administration of MSCs, stoma output was measured at 40mls/kg/24hours. The patient was receiving total parenteral nutrition (TPN) and showed no evidence of absorption of immunosuppressive drugs. Effluent and histology from the stoma showed Candida and Noroviral infection with loss of absorptive surface epithelium. Serum citrulline levels ranged between 5-9micromol/l. Infusion of MSCs was well tolerated with no immediate or late side effects. At 4 days following MSC infusion, the patient's GI output decreased to 25mls/kg/24hours and her serum citrulline increased to 15.4micromol/l. An endoscopy performed 11 days post- administration of the cells demonstrated marked macroscopic improvement with rudimentary villi. The histological findings demonstrated significant regeneration of epithelium, villi and lamina propria. Enteral feeding was recommenced with improvement in nutritional parameters. At 30 days following administration, the patient continued to have reduced GI output and was clinically well with a serum citrulline level of 45micromol/l.
We have demonstrated that MSC therapy in the setting of inflammation from Candida and Noroviral infection was effective in triggering a regenerative process. It was well tolerated and early results are promising.