Over the past decades, mesenchymal stem cell (MSC)-based therapy has been intensively investigated and shown promising results in the treatment of various diseases due to their easy isolation, multiple lineage differentiation potential and immunomodulatory effects. To date, hundreds of phase I and II clinical trials using MSCs have been completed and many are ongoing. Accumulating evidence has shown that transplanted allogeneic MSCs lose their beneficial effects due to immunorejection. Nevertheless, the function of autologous MSCs is adversely affected by age, a process termed senescence, thus limiting their therapeutic potential. Despite great advances in knowledge, the potential mechanisms underlying MSC senescence are not entirely clear. Understanding the molecular mechanisms that contribute to MSC senescence is crucial when exploring novel strategies to rejuvenate senescent MSCs. In this review, we aim to provide an overview of the biological features of senescent MSCs and the recent progress made regarding the underlying mechanisms including epigenetic changes, autophagy, mitochondrial dysfunction and telomere shortening. We also summarize the current approaches to rejuvenate senescent MSCs including gene modification and pretreatment strategies. Collectively, rejuvenation of senescent MSCs is a promising strategy to enhance the efficacy of autologous MSC-based therapy, especially in elderly patients.

BackgroundMutations of EGFR and K-ras are biomarkers for predicting the efficacy of targeting agents in non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). Data on the gene mutation status of EGFR and K-ras in Chinese patients with CRC are limited.MethodsEGFR mutations in exon 18-21 and K-ras mutations in exon 1 and 2 were detected in tumor samples from 101 Chinese patients with CRC by polymerase chain reaction-single strand conformational polymorphism. The relationship between patients' characteristics and survival time and gene mutation status were analyzed using the Statistical Package for the Social Sciences.ResultsOnly two samples (2.0%) had EGFR mutations in exon 18 or 21, and 33 of 101 samples (32.7%) had K-ras mutations in codon 12, 13, 45, 69, or 80. Univariate analysis suggested that differentiation might be correlated with K-ras mutations (p = 0.05), which was confirmed by a logistic regression model (p = 0.04). The median overall survival (OS) and median survival after metastasis were 44.0 and 18.0 months, respectively, in the mutant K-ras group, and 53.3 and 19.0 months, respectively, in the wild K-ras group. K-ras mutation was not an independent prognostic factor for OS or survival after metastasis (p = 0.79 and 0.78, respectively).ConclusionsIn Chinese patients with CRC, EGFR mutations were rare, and K-ras mutations were similar to those of Europeans. New mutations in codons 45, 69, and 80 were found in the Chinese population. Poor differentiation was an independent factor related to K-ras mutations.

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