Human adipose tissue-derived mesenchymal stem cells alleviate atopic dermatitis via regulation of B lymphocyte maturation

// Tae-Hoon Shin 1, 2, * , Byung-Chul Lee 1, 2, * , Soon Won Choi 1, 2 , Ji-Hee Shin 1, 2 , Insung Kang 1, 2 , Jin Young Lee 1, 2 , Jae-Jun Kim 1, 2 , Hong-Ki Lee 3 , Jae-Eon Jung 3 , Yong-Woon Choi 3 , Sung-Hoon Lee 3 , Jin-Sang Yoon 3 , Jin-Sub Choi 3 , Chi-Seung Lee 4, 5 , Yoojin Seo 1, 4, 5 , Hyung-Sik Kim 1, 4, 5 , Kyung-Sun Kang 1, 2 1 Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul 08826, South Korea 2 Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, South Korea 3 Biotechnology Institute, EHL-BIO Co., Ltd., Uiwang 16006, South Korea 4 School of Medicine, Pusan National University, Busan 49241, South Korea 5 Biomedical Research Institute, Pusan National University Hospital, Busan 49241, South Korea * These authors contributed equally to this work Correspondence to: Kyung-Sun Kang, email: kangpub@snu.ac.kr Hyung-Sik Kim, email: hskimcell@pusan.ac.kr Keywords: mesenchymal stem cells, atopic dermatitis, B cell maturation, mast cell degranulation, distribution Received: June 06, 2016      Accepted: November 12, 2016      Published: November 19, 2016 ABSTRACT Mesenchymal stem cell (MSC) has been applied for the therapy of allergic disorders due to its beneficial immunomodulatory abilities. However, the underlying mechanisms for therapeutic efficacy are reported to be diverse according to the source of cell isolation or the route of administration. We sought to investigate the safety and the efficacy of human adipose tissue-derived MSCs (hAT-MSCs) in mouse atopic dermatitis (AD) model and to determine the distribution of cells after intravenous administration. Murine AD model was established by multiple treatment of Dermatophagoides farinae . AD mice were intravenously infused with hAT-MSCs and monitored for clinical symptoms. The administration of hAT-MSCs reduced the gross and histological signatures of AD, as well as serum IgE level. hAT-MSCs were mostly detected in lung and heart of mice within 3 days after administration and were hardly detectable at 2 weeks. All of mice administered with hAT-MSCs survived until sacrifice and did not demonstrate any adverse events. Co-culture experiments revealed that hAT-MSCs significantly inhibited the proliferation and the maturation of B lymphocytes via cyclooxygenase (COX)-2 signaling. Moreover, mast cell (MC) degranulation was suppressed by hAT-MSC. In conclusion, the intravenous infusion of hAT-MSCs can alleviate AD through the regulation of B cell function.