Graft infusion of adipose‐derived mesenchymal stromal cells to prevent rejection in experimental intestinal transplantation: A feasibility study

• DOI: 10.1111/ctr.14226
• Publication Date: 2021-01-19T23:36:46Z
• Authors: Ane M. Andres; Pablo Stringa; Paloma Talayero; Monica Santamaria; Mariano García‐Ar...; Soledad García Gó...; Carlota Largo‐Ara...; Rosa M. Aras‐Lopez; Maria Teresa Vall...; Laura Guerra Past...; Luz Vega; Jose Luis Encinas; Manuel Lopez‐Sant...; Francisco Hernánd...
• Keywords: Graft Rejection; Immunosuppression Therapy; 0301 basic medicine; Mesenchymal Stem Cells; Mesenchymal Stem Cell Transplantation; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; REJECTION; SMALL BOWEL TRANSPLANTATION; https://purl.org/becyt/ford/3.1; Animals; Feasibility Studies; Humans; ADIPOSE-DERIVED MESENCHYMAL STROMAL CELLS; https://purl.org/becyt/ford/3

AbstractBackgroundMesenchymal stromal cells (MSC) have been proposed as a promising complement to standard immunosuppression in solid organ transplantation because of their immunomodulatory properties. The present work addresses the role of adipose‐derived MSC (Ad‐MSC) in an experimental model of acute rejection in small bowel transplantation (SBT).Material/MethodsHeterotopic allogeneic SBT was performed. A single dose of 1.5x106 Ad‐MSC was intra‐arterially delivered just before graft reperfusion. Animals were divided into CONTROL (CTRL), CONTROL+Ad‐MSC (CTRL_MSC), tacrolimus (TAC), and TAC+Ad‐MSC (TAC_MSC) groups. Each Ad‐MSC groups was subdivided in autologous and allogeneic third‐party groups.ResultsRejection rate and severity were similar in MSC‐treated and untreated animals. CTRL_MSC animals showed a decrease in macrophages, T‐cell (CD4, CD8, and Foxp3 subsets) and B‐cell counts in the graft compared with CTRL, this decrease was attenuated in TAC_MSC animals. Pro‐ and anti‐inflammatory cytokines and some chemokines and growth factors increased in CTRL_MSC animals, especially in the allogeneic group, whereas milder changes were seen in the TAC groups.ConclusionAd‐MSC did not prevent rejection when administered just before reperfusion. However, they showed immunomodulatory effects that could be relevant for a longer‐term outcome. Interference between tacrolimus and the MSC effects should be addressed in further studies.