Oncotarget

Research Papers: Immunology:

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, Jinhua Sun, Feng Wang, Yan Li, Jianzhong Bi and Tingyu Qu _

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Oncotarget. 2016; 7:72537-72545. https://doi.org/10.18632/oncotarget.12345

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Abstract

Hongna Yang1,2, Jinhua Sun2, Feng Wang2, Yan Li2, Jianzhong Bi3 and Tingyu Qu2,4

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+CD127low/- 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 (naïve) 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 naïve 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.


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