scholarly journals Programmed Cell Death Ligand 1-Transfected Mouse Bone Marrow Mesenchymal Stem Cells as Targeted Therapy for Rheumatoid Arthritis

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Qiong-ying Hu ◽  
Yun Yuan ◽  
Yu-chen Li ◽  
Lu-yao Yang ◽  
Xiang-yu Zhou ◽  
...  

Programmed cell death 1 ligand (PD-L1) and its receptor (PD-1) are key molecules for immunoregulation and immunotherapy. PD-L1 binding PD-1 is an effective way to regulate T or B cell immunity in autoimmune diseases such as rheumatoid arthritis (RA). In our study, we overexpressed PD-L1 by constructing a recombinant of PD-L1-lentiviral vector, which was subsequently used to transfect mouse bone marrow mesenchymal stem cells (MBMMSCs) and significantly suppressed the development of collagen-induced arthritis (CIA) in DBA/1j mice. In addition, PD-L1-transfected MBMMSCs (PD-L1-MBMMSCs) ameliorated joint damage, reduced proinflammatory cytokine expression, and inhibited T and B cell activation. Furthermore, PD-L1-MBMMSCs decreased the number of dendritic cells and increased the numbers of regulatory T cells and regulatory B cells in joints of CIA mice. In conclusion, our results provided a potential therapeutic strategy for RA treatment with PD-L1-MBMMSC-targeted therapy.

2016 ◽  
Vol 19 (2) ◽  
pp. 111-116
Author(s):  
Rafal Hussamildeen Abdullah ◽  
◽  
Shahlla Mahdi Salih ◽  
Nahi Yosef Yaseen ◽  
Ahmed Majeed Al-Shammari ◽  
...  

2008 ◽  
Vol 22 (4) ◽  
pp. 995-1001 ◽  
Author(s):  
Shabnam Kermani ◽  
Khadijeh Karbalaie ◽  
Seyed Hossein Madani ◽  
Ali Akbar Jahangirnejad ◽  
Mohamadreza Baghaban Eslaminejad ◽  
...  

2007 ◽  
Vol 293 (5) ◽  
pp. C1561-C1567 ◽  
Author(s):  
Rong Tao ◽  
Chu-Pak Lau ◽  
Hung-Fat Tse ◽  
Gui-Rong Li

Bone marrow mesenchymal stem cells (MSCs) are used as a cell source for cardiomyoplasty; however, the cellular electrophysiological properties are not fully understood. The present study was to investigate the functional ionic channels in undifferentiated mouse bone marrow MSCs using whole cell patch-voltage clamp technique, RT-PCR, and Western immunoblotting analysis. We found that three types of ionic currents were present in mouse MSCs, including a Ca2+-activated K+ current ( IKCa), an inwardly rectifying K+ current ( IKir), and a chloride current ( ICl). IKir was inhibited by Ba2+, and IKCa was activated by the Ca2+ ionophore A-23187 and inhibited by the intermediate-conductance IKCa channel blocker clotrimazole. ICl was activated by hyposmotic (0.8 T) conditions and inhibited by the chloride channel blockers DIDS and NPPB. The corresponding ion channel genes and proteins, KCa3.1 for IKCa, Kir2.1 for IKir, and Clcn3 for ICl, were confirmed by RT-PCR and Western immunoblotting analysis in mouse MSCs. These results demonstrate that three types of functional ion channel currents (i.e., IKir, IKCa, and ICl) are present in mouse bone marrow MSCs.


2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Jean-Marie Berthelot ◽  
Benoit Le Goff ◽  
Yves Maugars

Abstract Background Bone marrow mesenchymal stem cells (BM-MSCs) can dampen inflammation in animal models of inflammatory rheumatisms and human osteoarthritis. They are expected to be a solution for numerous human conditions. However, in rheumatoid arthritis (RA) and spondyloarthritis (SpA), subsets of subchondral BM-MSCs might conversely fuel synovitis and enthesitis. Main text Abnormal behaviour of BM-MSCs and/or their progeny has been found in RA and SpA. BM-MSCs also contribute to the ossifying processes observed in ankylosing spondylitis. Some synovial fibroblastic stem cells probably derive from BM-MSCs, but some stem cells can also migrate through the bare zone area of joints, not covered by cartilage, into the synovium. BM-MSCs can also migrate in the synovium over tendons. Sub-populations of bone marrow stem cells also invade the soft tissue side of enthesis via small holes in the bone cortex. The present review aims (1) to make a focus on these two aspects and (2) to put forward the hypothesis that lasting epigenetic changes of some BM-MSCs, induced by transient infections of the bone marrow close to the synovium and/or entheses (i.e. trained immunity of BM-MSCs and/or their progeny), contribute to the pathogenesis of inflammatory rheumatisms. Such hypothesis would fit with (1) the uneven distribution and/or flares of arthritis and enthesitis observed at the individual level in RA and SpA (reminiscent of what is observed following reactive arthritis and/or in Whipple’s disease); (2) the subchondral bone marrow oedema and erosions occurring in many RA patients, in the bare zone area; and (3) the frequent relapses of RA and SpA despite bone marrow transplantation, whereas most BM-MSCs resist graft preconditioning. Conclusion Some BM-MSCs might be more the problem than the solution in inflammatory rheumatisms. Subchondral bone marrow BM-MSCs and their progeny trafficking through the bare zone area of joints or holes in the bone cortex of entheses should be thoroughly studied in RA and SpA respectively. This may be done first in animal models. Mini-arthroscopy of joints could also be used in humans to specifically sample tissues close to the bare zone and/or enthesis areas.


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