Abstract
Mesenchymal stem cells (MSCs) are multipotent stromal cells with immunomodulatory properties. They have emerged as a very promising treatment for autoimmunity and inflammatory diseases such as rheumatoid arthritis. Previous studies have demonstrated that MSCs, administered systemically, migrate to lymphoid tissues associated with the inflammatory site where functional MSC-induced immune cells with a regulatory phenotype were increased mediating the immunomodulatory effects of MSCs. These results suggest that homing of MSCs to the lymphatic system plays an important role in the mechanism of action of MSCs in vivo. Thus, we hypothesized that direct intralymphatic (IL) (also referred as intranodal) administration of MSCs could be an alternative and effective route of administration for MSC-based therapy. Here, we report the feasibility and efficacy of the IL administration of human expanded adipose mesenchymal stem cells (eASCs) in a mouse model of collagen-induced arthritis (CIA). IL administration of eASCs attenuated the severity and progression of arthritis, reduced bone destruction and increased the levels of regulatory T cells (CD25+Foxp3+CD4+ cells) and Tr1 cells (IL10+CD4+), in spleen and draining lymph nodes. Taken together, these results indicate that IL administration of eASCs is very effective in modulating established CIA and may represent an alternative treatment modality for cell therapy with eASCs.
Highlights
Mesenchymal stem cells (MSCs), which can be obtained from several adult tissues [1,2,3,4,5], have a potential use for cell therapy in inflammatory diseases based on their immunomodulatory properties and paracrine anti-fibrotic, anti-apoptotic, and pro-angiogenic effects [6,7,8]
We investigated the feasibility and efficacy of the expanded adipose mesenchymal stem cells (eASCs) administration into the lymph nodes in collagen-induced arthritis (CIA) mice and compared it with the IV administration
To first demonstrate the feasibility and efficacy of the IL administration of eASCs, CIA mice were injected at day 1, day 8, and day 15 in the right and left inguinal lymph nodes with either eASCs (5 × 104 cells per lymph node; total dose per time point: 1 × 105) or Ringer’s lactate, and the clinical score was monitored for 50 days after the treatment
Summary
Mesenchymal stem cells (MSCs), which can be obtained from several adult tissues [1,2,3,4,5], have a potential use for cell therapy in inflammatory diseases based on their immunomodulatory properties and paracrine anti-fibrotic, anti-apoptotic, and pro-angiogenic effects [6,7,8]. The therapeutic effects of MSCs have been demonstrated in experimental animal models of a wide variety of inflammatory diseases [10,11,12,13,14,15,16,17]. Mainly the intravenous (IV) or intraperitoneal routes of administration have been used [10, 25, 26], while the IV route of administration is routinely used in the clinical practice, allowing a systemic delivery of the therapeutic product. Previous studies have demonstrated that systemically administered MSCs homed to lymphoid tissues associated with the inflammatory site where functional MSC-induced immune cells with regulatory phenotype (i.e., regulatory T cells) were increased, mediating the immunomodulatory effects of MSCs [10, 11, 27, 28]
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