Effects of high glucose on mesenchymal stem cell proliferation and differentiation.
High glucose (HG) concentrations impair cellular functions and induce apoptosis. Exposition of mesenchymal stem cells (MSC) to HG was reported to reduce colony forming activity and induce premature senescence. We characterized the effects of HG on human MSC in vitro using telomerase-immortalized MSC (hMSC-TERT) and primary MSC (hMSC). HG (25mM) enhanced hMSC-TERT proliferation in long-term studies in contrast to hMSC where proliferation was unchanged. Thioredoxin-interacting protein, which is involved in apoptosis regulation, was stimulated by glucose in hMSC-TERT. However, apoptosis was not influenced by HG in both cell types. MSC treatment with HG favored osteogenic differentiation. MSC are resistant to HG toxicity, depending on the stemness of MSC. Proliferation and osteogenic differentiation are stimulated by HG. Effects of HG on the transient amplifying compartment of MSC may differ from those in mature cells. Further research is needed to unravel the molecular mechanisms of HG resistance of MSC.
Li
Yu-Ming
YM
Orthopedic Center for Musculoskeletal Research, Orthopedic Department, University of Würzburg, Brettreichstrasse 11, D-97074 Würzburg, Germany.
Schilling
Tatjana
T
Benisch
Peggy
P
Zeck
Sabine
S
Meissner-Weigl
Jutta
J
Schneider
Doris
D
Limbert
Catarina
C
Seufert
Jochen
J
Kassem
Moustapha
M
Schütze
Norbert
N
Jakob
Franz
F
Ebert
Regina
R
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000008:administration & dosage*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*
D002352:Carrier Proteins; C486715:TXNIP protein, human; D005947:Glucose