Premature senescence of bone marrow-derived mesenchymal stem cells (BMSC) remains a major concern for their application clinically. Hedgehog signaling has been reported to regulate aging-associated markers and MSC skewed differentiation. Indian Hedgehog (IHH) is a ligand of Hedgehog intracellular pathway considered as an inducer in chondrogenesis of human BMSC. However, the role of IHH in the aging of BMSC is still unclear. This study explored the role IHH in the senescence of BMSC obtained from human samples and senescent mice. Isolated BMSC were transfected with IHH siRNA or incubated with exogenous IHH protein and the mechanisms of aging and differentiation investigated. Moreover, the interactions between IHH, and mammalian target of rapamycin (mTOR) and reactive oxygen species (ROS) were evaluated using the corresponding inhibitors and antioxidants. BMSC transfected with IHH siRNA showed characteristics of senescence-associated features including increased senescence-associated β-galactosidase activity (SA-β-gal), induction of cell cycle inhibitors (p53/p16), development of senescence-associated secretory phenotype (SASP), activation of ROS and mTOR pathways as well as the promotion of skewed differentiation. Interestingly, BMSC treatment with IHH protein reversed the senescence markers and corrected biased differentiation. Moreover, IHH shortage-induced senescence signs were compromised after mTOR and ROS inhibition. Our findings presented anti-aging activity for IHH in BMSC through down-regulation of ROS/mTOR pathways. This discovery might contribute to increasing the therapeutic, immunomodulatory and regenerative potency of BMSC and introduce a novel remedy in the management of aging-related diseases.

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PurposeThe purpose of this paper is to provide an introduction to three articles from Reference Services Review on the theme of library outreach to international students. It aims to give a summary overview of the current research on international students and library outreach and to introduce and contextualize the three articles.Design/methodology/approachThis paper frames the three articles and places them in the context of the exhaustive literature on the topic.FindingsInternational students are not all alike. Grouping all of these students together under the umbrella term of “international student” contributes little, if at all, to the understanding of their real needs and problems.Practical implicationsThis paper suggests that there are still areas for further exploration on the topic of international students and library outreach.Originality/valueThis paper argues with the oversimplified and generalized approach to international students, and suggests that it is not the most useful way to assist individual students.

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