Biodistribution and Efficacy of Human Adipose-Derived Mesenchymal Stem Cells Following Intranodal Administration in Experimental Colitis
| Autor: | Mercedes Lopez-Santalla, Pablo Mancheño-Corvo, Amelia Escolano, Ramon Menta, Olga DelaRosa, Jose Luis Abad, Dirk Büscher, Juan M. Redondo, Juan A. Bueren, Wilfried Dalemans, Eleuterio Lombardo, Marina I. Garin |
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| Přispěvatelé: | European Commission |
| Rok vydání: | 2016 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
0301 basic medicine Pathology medicine.medical_specialty EXPERIMENTAL ARTHRITIS Efficacy colitis Immunology efficacy Adipose tissue immunomodulation DENDRITIC CELLS THERAPY CLINICAL-TRIAL Immunomodulation Cell therapy 03 medical and health sciences Route of administration Biodistribution 0302 clinical medicine Immune system intranodal therapy Adipose-derived mesenchymal stem cells Immunology and Allergy Medicine SYSTEMIC-LUPUS-ERYTHEMATOSUS Colitis biodistribution Original Research adipose-derived mesenchymal stem cells business.industry Mesenchymal stem cell IN-VITRO medicine.disease 3. Good health LYMPHOCYTE-PROLIFERATION 030104 developmental biology Lymphatic system ANIMAL-MODELS STROMAL CELLS 030220 oncology & carcinogenesis Intranodal therapy Lymph lcsh:RC581-607 business INFLAMMATORY-BOWEL-DISEASE |
| Zdroj: | Frontiers in Immunology Repisalud Instituto de Salud Carlos III (ISCIII) Frontiers in Immunology, Vol 8 (2017) |
| ISSN: | 1664-3224 |
| Popis: | 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. European Community's 7th Framework Program for the collaborative project: ``REGENER-AR: Bringing Regenerative Medicine into the market: Allogeneic eASCs Phase IB/IIA clinical trial for treating Rheumatoid Arthritis (contract no. 279174 EC). Sí |
| Databáze: | OpenAIRE |
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