Toll‑like receptor 9 agonist stimulation enables osteogenic differentiation without altering the immune status of umbilical cord mesenchymal stem cells.
Mesenchymal stem cells (MSCs) possess three characteristics critical to tissue regeneration; multipotency, low immunogenicity and an undifferentiated status, providing plasticity. However, increasing evidence has indicated that induction of an immune response in vivo can injure and reject MSC‑based tissues. Toll‑like receptors (TLRs) are a family of pathogen‑associated pattern recognition receptors, which are important in bridging the innate and adaptive immune responses. TLRs have been demonstrated to exhibit important MSC biological regulatory functions in previous studies. To confirm the role of TLR9 in the immune status maintenance of MSCs isolated from umbilical cords, the present study performed assessments to detect agonist effects. Following addition of the TLR9 agonist, CpG, to an umbilical cord mesenchymal stem cell (UCMSC) culture medium, a number of methods were used to detect the changes in the biological function of the UCMSCs. Reverse transcription‑quantitative polymerase chain reaction indicated increased levels of pro‑inflammatory molecules and decreased expression levels of stem cell markers following exposure to the TLR9 agonist. However, flow cytometry revealed that activation of TLR9 had no effect on the proliferation of peripheral blood leukocytes or the expression of surface markers. The present study also identified that CpG‑oligodeoxynucleotide promoted MSC osteogenic differentiation, while inhibiting MSC proliferation and migration. These results indicated that TLRs and their ligands may serve as regulators of MSC proliferation and differentiation, and affect the maintenance of MSC multipotency.
Laboratory of Pathology, Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Yongfeng
Y
Yang
Laboratory of Pathology, Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Yanwen
Y
Wang
Laboratory of Pathology, Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Li
L
Li
Laboratory of Pathology, Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Ji
J
Bao
Laboratory of Pathology, Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Fei
F
Chen
Laboratory of Pathology, Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Li
L
Zhang
D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018899:CpG Islands; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003857:Deoxyuridine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D010012:Osteogenesis; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D014470:Umbilical Cord / Q000166:cytology
D015415:Biomarkers; D016207:Cytokines; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; C031086:5-ethynyl-2'-deoxyuridine; D003857:Deoxyuridine