title: Human tendon stem cells better maintain their stemness in hypoxic culture conditions.
abstract: Tissues and organs in vivo are under a hypoxic condition; that is, the oxygen tension is typically much lower than in ambient air. However, the effects of such a hypoxic condition on tendon stem cells, a recently identified tendon cell, remain incompletely defined. In cell culture experiments, we subjected human tendon stem cells (hTSCs) to a hypoxic condition with 5% O2, while subjecting control cells to a normaxic condition with 20% O2. We found that hTSCs at 5% O2 had significantly greater cell proliferation than those at 20% O2. Moreover, the expression of two stem cell marker genes, Nanog and Oct-4, was upregulated in the cells cultured in 5% O2. Finally, in cultures under 5% O2, more hTSCs expressed the stem cell markers nucleostemin, Oct-4, Nanog and SSEA-4. In an in vivo experiment, we found that when both cell groups were implanted with tendon-derived matrix, more tendon-like structures formed in the 5% O2 treated hTSCs than in 20% O2 treated hTSCs. Additionally, when both cell groups were implanted with Matrigel, the 5% O2 treated hTSCs showed more extensive formation of fatty, cartilage-like and bone-like tissues than the 20% O2 treated cells. Together, the findings of this study show that oxygen tension is a niche factor that regulates the stemness of hTSCs, and that less oxygen is better for maintaining hTSCs in culture and expanding them for cell therapy of tendon injuries.
authors.affiliation: MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Jianying
authors.initials: J
authors.lastname: Zhang
authors.forename: James H-C
authors.initials: JH
authors.lastname: Wang
mesh_terms: D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D055746:Stage-Specific Embryonic Antigens / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D013710:Tendons / Q000166:cytology*
chemical_list: D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D055746:Stage-Specific Embryonic Antigens; C066584:stage-specific embryonic antigen-4