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Graft infusion of adipose‐derived mesenchymal stromal cells to prevent rejection in experimental intestinal transplantation: A feasibility study
Author(s) -
Andres Ane M.,
Stringa Pablo,
Talayero Paloma,
Santamaria Monica,
GarcíaArranz Mariano,
García GómezHeras Soledad,
LargoAramburu Carlota,
ArasLopez Rosa M.,
VallejoCremades Maria Teresa,
Guerra Pastrián Laura,
Vega Luz,
Encinas Jose Luis,
LopezSantamaria Manuel,
HernándezOliveros Francisco
Publication year - 2021
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/ctr.14226
Subject(s) - medicine , mesenchymal stem cell , transplantation , immunosuppression , tacrolimus , adipose tissue , foxp3 , stromal cell , cd8 , immunology , immune system , pathology , surgery
Abstract Background Mesenchymal 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/Methods Heterotopic 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. Results Rejection 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. Conclusion Ad‐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.