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oai:repisalud.isciii.es:20.500.12105/51122024-09-27T09:16:02Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Lopez-Santalla, Mercedes author Mancheno-Corvo, Pablo author Escolano, Amelia author Menta, Ramon author DelaRosa, Olga author Luis Abad, Jose author Buscher, Dirk author Redondo, Juan Miguel author Bueren, Juan A. author Dalemans, Wilfried author Lombardo, Eleuterio author Garin, Marina I. author 2017 Mesenchymal stem cells (MSCs) have a large potential in cell therapy for treatment of inflammatory and autoimmune diseases, thanks to their immunomodulatory properties. The encouraging results in animal models have initiated the translation of MSC therapy to clinical trials. In cell therapy protocols with MSCs, administered intravenously, several studies have shown that a small proportion of infused MSCs can traffic to the draining lymph nodes (LNs). This is accompanied with an increase of different types of regulatory immune cells in the LNs, suggesting the importance of migration of MSCs to the LNs in order to contribute to immunomodulatory response. Intranodal (IN), also referred as intralymphatic, injection of cells, like dendritic cells, is being proposed in the clinic for the treatment of cancer and allergy, showing that this route of administration is clinically safe and efficient. In this study, we investigated, for the first time, the biodistribution and the efficacy of Luciferase+adipose-derived MSCs (Luci-eASCs), infused through the inguinal LNs (iLNs), in normal mice and in inflamed mice with colitis. Most of the LucieASCs remain in the iLNs and in the adipose tissue surrounding the inguinal LNs. A small proportion of Luci-eASCs can migrate to other locations within the lymphatic system and to other tissues and organs, having a preferential migration toward the intestine in colitic mice. Our results show that the infused Luci-eASCs protected 58\% of the mice against induced colitis. Importantly, a correlation between the response to eASC treatment and a higher accumulation of eASCs in popliteal, parathymic, parathyroid, and mesenteric LNs were found. Altogether, these results suggest that IN administration of eASCs is feasible and may represent an effective strategy for cell therapy protocols with human adipose-derived MSCs in the clinic for the treatment of immune-mediated disorders. Front Immunol. 2017; 8:638 1664-3224 http://hdl.handle.net/20.500.12105/5112 28642759 10.3389/fimmu.2017.00638 Frontiers in Immunology Adipose-derived mesenchymal stem cells Intranodal therapy Colitis Biodistribution Efficacy Immunomodulation SYSTEMIC-LUPUS-ERYTHEMATOSUS INFLAMMATORY-BOWEL-DISEASE STROMAL CELLS LYMPHOCYTE-PROLIFERATION EXPERIMENTAL ARTHRITIS DENDRITIC CELLS CLINICAL-TRIAL ANIMAL-MODELS IN-VITRO THERAPY Biodistribution and efficacy of human adipose-Derived Mesenchymal stem cells Following intranodal administration in experimental colitis