PMID- 31382595
OWN - NLM
STAT- MEDLINE
DCOM- 20200511
LR  - 20200511
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 8
IP  - 8
DP  - 2019 Aug 3
TI  - Combination Therapy of Mesenchymal Stromal Cells and Interleukin-4 Attenuates 
      Rheumatoid Arthritis in a Collagen-Induced Murine Model.
LID - 10.3390/cells8080823 [doi]
LID - 823
AB  - Rheumatoid arthritis (RA) is a disease of the joints that causes decreased 
      quality of life. Mesenchymal stromal cells (MSCs) have immunosuppressive 
      properties, with possible use in the treatment of RA. Similarly, interleukin 
      (IL)-4 has been shown as a potential RA treatment. However, their combination has 
      not been explored before. Therefore, this study aimed to investigate the effect 
      of a combination therapy of MSCs and IL-4 in the treatment of RA, using a murine 
      collagen-induced arthritis (CIA) model. Arthritis was induced in Balb/c mice by 
      two intradermal injections of type II collagen (CII), at days 0 and 21. CIA mice 
      were randomly assigned to four groups; group I received an intravenous injection 
      of mouse bone marrow-derived MSCs, while group II received an intraperitoneal 
      injection of IL-4. Group III received a combined treatment of MSC and IL-4, while 
      group IV served as a CIA diseased control group receiving phosphate buffer saline 
      (PBS). A fifth group of healthy mice served as the normal healthy control. To 
      assess changes induced by different treatments, levels of RA-associated 
      inflammatory cytokines and biomarkers were measured in the serum, knee joints, 
      and synovial tissue, using ELISA and Real Time-qPCR. Histopathological features 
      of knee joints were analyzed for all groups. Results showed that combined MSC and 
      IL-4 treatment alleviated signs of synovitis in CIA mice, reverting to the values 
      of healthy controls. This was evident by the decrease in the levels of rheumatic 
      factor (RF), C-reactive protein (CRP) and anti-nuclear antibodies (ANA) by 64, 
      80, and 71%, respectively, compared to the diseased group. Moreover, tumor 
      necrosis factor-alpha (TNF- alpha) and monocyte chemoattractant protein-1 (MCP-1) 
      levels decreased by 63 and 68%, respectively. Similarly, our gene expression data 
      showed improvement in mice receiving combined therapy compared to other groups 
      receiving single treatment, where cartilage oligomeric matrix protein (Comp), 
      tissue inhibitor metalloproteinase-1 (Timp1), matrix metalloproteinase1 (Mmp-1), 
      and IL-1 receptor (Il-1r) gene expression levels decreased by 75, 70, and 78%, 
      respectively. Collectively, treatment with a combined therapy of MSC and IL-4 
      might have an efficient therapeutic effect on arthritis. Thus, further studies 
      are needed to assess the potential of different MSC populations in conjugation 
      with IL-4 in the treatment of experimental arthritis.
FAU - Haikal, Shaimaa M
AU  - Haikal SM
AD  - Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, 
      Cairo 11562, Egypt.
FAU - Abdeltawab, Nourtan F
AU  - Abdeltawab NF
AUID- ORCID: 0000-0002-1290-2197
AD  - Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, 
      Cairo 11562, Egypt. nourtan.abdeltawab@pharma.cu.edu.eg.
FAU - Rashed, Laila A
AU  - Rashed LA
AD  - Department of Biochemistry and Molecular Biology, Faculty of Medicine, Cairo 
      University, Cairo 11562, Egypt.
FAU - Abd El-Galil, Tarek I
AU  - Abd El-Galil TI
AUID- ORCID: 0000-0003-2217-7045
AD  - Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, 
      Cairo 11562, Egypt.
FAU - Elmalt, Heba A
AU  - Elmalt HA
AD  - Department of Medical Biochemistry, National Research Center, Cairo 11562, Egypt.
FAU - Amin, Magdy A
AU  - Amin MA
AD  - Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, 
      Cairo 11562, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20190803
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 207137-56-2 (Interleukin-4)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Animals
MH  - Arthritis, Experimental
MH  - Arthritis, Rheumatoid/chemically induced/*therapy
MH  - Biomarkers/*metabolism
MH  - Collagen
MH  - Cytokines/*metabolism
MH  - Disease Models, Animal
MH  - Interleukin-4/*pharmacology
MH  - Male
MH  - *Mesenchymal Stem Cell Transplantation
MH  - Mice
MH  - Mice, Inbred BALB C
PMC - PMC6721641
OTO - NOTNLM
OT  - IL-4
OT  - auto-inflammatory disease
OT  - collagen-induced arthritis
OT  - cytokines
OT  - inflammatory mediators
OT  - mesenchymal stem cells
OT  - mouse model
OT  - rheumatoid arthritis
COIS- The authors declare no conflict of interest.
EDAT- 2019/08/07 06:00
MHDA- 2020/05/12 06:00
PMCR- 2019/08/01
CRDT- 2019/08/07 06:00
PHST- 2019/06/14 00:00 [received]
PHST- 2019/07/22 00:00 [revised]
PHST- 2019/07/23 00:00 [accepted]
PHST- 2019/08/07 06:00 [entrez]
PHST- 2019/08/07 06:00 [pubmed]
PHST- 2020/05/12 06:00 [medline]
PHST- 2019/08/01 00:00 [pmc-release]
AID - cells8080823 [pii]
AID - cells-08-00823 [pii]
AID - 10.3390/cells8080823 [doi]
PST - epublish
SO  - Cells. 2019 Aug 3;8(8):823. doi: 10.3390/cells8080823.