Hypoxia and low-dose inflammatory stimulus synergistically enhance bone marrow mesenchymal stem cell migration.
OBJECTIVE
Cell migration is necessary for numerous physiological cell processes. Although either inflammatory or hypoxic stimuli of certain dose and duration have positive influence on cell migration, their combination has not been shown to result in a synergistic effect.


METHODS
In this study, we investigated combined effects of hypoxia and low-dose inflammatory stimulus (one-tenth of that of a previously used concentration) on migration of human bone marrow-derived mesenchymal stem cells (BMMSCs).


RESULTS
Our results from real-time PCR, Western blot analysis and an immunofluorescence assay, showed that dual stimulation up-regulated CXCR4 expression. Based on tablet scratch experimentation and transwell assay, the dual stimuli exhibited greater positive effects on cell migration than a single inflammatory or hypoxic stimulus. When effects of various pre-treatments on cell proliferation, differentiation and immunosuppression were screened, cells subjected to the hypoxic stimulus or dual stimuli had increased cell proliferation, while short-term inflammatory stimulus and/or hypoxic stimulus had no negative effect on cell differentiation and immunosuppression.


CONCLUSIONS
These findings suggest that the combination of hypoxia and low-dose inflammatory stimuli enhances the potential of BMMSCs to migrate, thus identifying cell pre-treatment conditions that could enhance future stem cell-based therapeutics.
State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China.|Department of Stomatology, Jinan Military General Hospital, Jinan, Shandong Province, China.
Yang
Y
Yu
State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China.
Yuan
Y
Yin
State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China.
Rui-Xin
RX
Wu
State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China.
Xiao-Tao
XT
He
State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China.
Xi-Yu
XY
Zhang
State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China.
Fa-Ming
FM
Chen
D017209:Apoptosis / Q000187:drug effects; D001596:Benzylamines; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects; D015687:Cell Hypoxia; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000494:pharmacology*; D018920:Coculture Techniques; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D000080027:Cyclams; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008856:Microscopy, Fluorescence; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
D001596:Benzylamines; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D050659:Core Binding Factor Alpha 1 Subunit; D000080027:Cyclams; D006571:Heterocyclic Compounds; D047495:PPAR gamma; C493709:RUNX2 protein, human; D019718:Receptors, CXCR4; D015675:Osteocalcin; C088327:plerixafor
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