Inducible immortality in hTERT‐human mesenchymal stem cells

Human mesenchymal stem cells (hMSCs) are attractive candidates for tissue engineering and cell‐based therapy because of their multipotentiality and availability in adult donors. However, in vitro expansion and differentiation of these cells is limited by replicative senescence. The proliferative capacity of hMSCs can be enhanced by ectopic expression of telomerase, allowing for long‐term culture. However, hMSCs with constitutive telomerase expression demonstrate unregulated growth and even tumor formation. To address this problem, we used an inducible Tet‐On gene expression system to create hMSCs in which ectopic telomerase expression can be induced selectively by the addition of doxycycline (i‐hTERT hMSCs). i‐hTERT hMSCs have inducible hTERT expression and telomerase activity, and are able to proliferate significantly longer than wild type hMSCs when hTERT expression is induced. They stop proliferating when hTERT expression is turned off and can be rescued when expression is re‐induced. They retain multipotentiality in vitro even at an advanced age. We also used a selective inhibitor of telomere elongation to show that the mechanism driving immortalization of hMSCs by hTERT is dependent upon maintenance of telomere length. Thanks to their extended lifespan, preserved multipotentiality and controlled growth, i‐hTERT hMSCs may prove to be a useful tool for the development and testing of novel stem cell therapies. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1879–1885, 2012     

Impact of Clinical and Pathohistological Characteristics on the Incidence of Recurrence and Survival in Elderly Patients with Gastric Cancer

Background  

Gastric cancer is one of the most frequent malignant tumors worldwide. Despite improvements in diagnostic procedures, as well as the introduction of multimodal treatment strategies, the overall prognosis remains poor. The role of gastric resection in elderly patients with gastric cancer has not been clearly defined as yet. The goal of the present study was to assess whether specific pathohistological features result in different outcomes for younger patients and elderly patients.