Effects of hypoxia on the immunomodulatory properties of human gingiva-derived mesenchymal stem cells.
The environment of bone marrow mesenchymal stem cells (MSCs) is hypoxic, which plays an important role in maintaining their self-renewal potential and undifferentiated state. MSCs have been proven to possess immunomodulatory properties and have been used clinically to treat autoimmune diseases. Here, we tested the effects of hypoxia on the immunomodulatory properties of MSCs and examined its possible underlying mechanisms. We found that hypoxic stimulation promoted the immunomodulatory properties of human gingiva-derived mesenchymal stem cells (hGMSCs) by enhancing the suppressive effects of hGMSCs on peripheral blood mononuclear cells (PBMCs). The proliferation of PBMCs was significantly inhibited, while the apoptosis of PBMCs was increased, which was associated with the Fas ligand (FasL) expression of hGMSCs. The in vivo study showed that systemically infused hGMSCs could enhance skin wound repair, and 24-h hypoxic stimulation significantly promoted the reparative capacity of hGMSCs. For mechanism, hGMSC treatment inhibited the local inflammation of injured skin by suppressing the inflammatory cells, reducing the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), and increasing anti-inflammatory cytokine interleukin-10 (IL-10), which was promoted by hypoxia. Hypoxia preconditioning may be a good optimizing method to promote the potential of MSCs for the future cell-based therapy.
State Key Laboratory of Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chendu, Sichuan, China.
C M
CM
Jiang
Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
J
J
Liu
State Key Laboratory of Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chendu, Sichuan, China.
J Y
JY
Zhao
State Key Laboratory of Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chendu, Sichuan, China.
L
L
Xiao
State Key Laboratory of Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chendu, Sichuan, China.
S
S
An
State Key Laboratory of Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chendu, Sichuan, China.
Y C
YC
Gou
Qingdao First Sanatorium of Jinan Military Distract of PLA, Qingdao Shandong, China.
H X
HX
Quan
Department of Orthodontics, Luzhou Medical College, Luzhou, Sichuan, China.
Q
Q
Cheng
State Key Laboratory of Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chendu, Sichuan, China.
Y L
YL
Zhang
State Key Laboratory of Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chendu, Sichuan, China.
W
W
He
State Key Laboratory of Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chendu, Sichuan, China.
Y T
YT
Wang
State Key Laboratory of Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chendu, Sichuan, China.
W J
WJ
Yu
State Key Laboratory of Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chendu, Sichuan, China.
Y F
YF
Huang
State Key Laboratory of Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chendu, Sichuan, China.
Y T
YT
Yi
State Key Laboratory of Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chendu, Sichuan, China.
Y
Y
Chen
State Key Laboratory of Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chendu, Sichuan, China wangjunv@scu.edu.cn.
J
J
Wang
D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D018929:Cell Culture Techniques; D015687:Cell Hypoxia / Q000276:immunology*; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy; D018920:Coculture Techniques; D053222:Fas Ligand Protein / Q000276:immunology; D005260:Female; D005881:Gingiva / Q000166:cytology* / Q000276:immunology; D006097:Granulation Tissue / Q000276:immunology; D006801:Humans; D056747:Immunomodulation / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D012867:Skin / Q000276:immunology / Q000293:injuries; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014945:Wound Healing / Q000276:immunology
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C508609:IL10 protein, human; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
Fas ligand protein; apoptosis; cell proliferation; immunomodulation; interleukin-10; oxygen