Umbilical cord-derived mesenchymal stem cells reversed the suppressive deficiency of T regulatory cells from peripheral blood of patients with multiple sclerosis in a co-culture - a preliminary study

// Hongna Yang 1,2 , Jinhua Sun 2 , Feng Wang 2 , Yan Li 2 , Jianzhong Bi 3 and Tingyu Qu 2,4 1 Department of Critical-Care Medicine, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, China 2 Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA 3 Department of Neurology, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong, China 4 R & D, Cell and Tissue Bank of Shandong Province, Jinan, Shandong, China Correspondence to: Tingyu Qu, email: // or // Keywords : umbilical cord mesenchymal stem cells, stem cell priming, multiple sclerosis, T regulatory cells, immunomodulation, Immunology and Microbiology Section, Immune response, Immunity Received : November 21, 2015 Accepted : September 12, 2016 Published : September 29, 2016 Abstract The immunoregulatory function of T regulatory cells (Tregs) is impaired in multiple sclerosis (MS). Recent studies have shown that umbilical cord-derived mesenchymal stem cells (UC-MSCs) exert regulatory effect on the functions of immune cells. Thus, we investigated whether UC-MSCs could improve the impaired function of Tregs from MS patients. Co-cultures of UC-MSCs with PBMCs of MS patients were performed for 3 days. Flow cytometry was used to determine the frequency of Tregs. A cell proliferation assay was used to evaluate the suppressive capacity of Tregs. ELISA was conducted for cytokine analysis in the co-cultures. Our results showed that UC-MSCs significantly increased the frequency of CD4 + CD25 + CD127 low/- Tregs in resting CD4 + T cells (p<0.01) from MS, accompanied by the significantly augmented production of cytokine prostaglandin E2, transforming growth factor (-β1, and interleukin-10, along with a reduced interferon-γ production in these co-cultures (p<0.05 - 0.01). More importantly, UC-MSC-primed Tregs of MS patients significantly inhibited the proliferation of PHA-stimulated autologous and allogeneic CD4 + CD25 - T effector cells (Teffs) from MS patients and healthy individuals compared to non-UC-MSC-primed (naive) Tregs from the same MS patients (p<0.01). Furthermore, no remarkable differences in suppressing the proliferation of PHA-stimulated CD4 + CD25 - Teffs was observed in UC-MSC-primed Tregs from MS patients and naive Tregs from healthy subjects. The impaired suppressive function of Tregs from MS can be completely reversed in a co-culture by UC-MSC modulation. This report is the first to demonstrate that functional defects of Tregs in MS can be repaired in vitro using a simple UC-MSC priming approach.