Mesenchymal stem cells (MSCs) from post-natal bone marrow possess tremendous potential for cell-mediated gene therapy in several disease processes, and recent reports have broadened the spectrum for therapeutic applications to cancer therapy. The evidence that sites of active tumorigenesis favor the homing of exogenous MSCs have support the rationale for developing engineered MSCs as a tool to track malignant tissues and deliver anticancer agents within the tumor microenvironment. Several reports have proven the efficiency of MSCs as cell carrier for in vivo delivery of various clinically relevant anticancer factors, including cytokines, interferon, pro-drugs or replicative adenovirus, and tumor growth inhibition following engraftment within or in the vicinity of tumor. The enthusiasm for MSCs is further reinforced by the striking observation that unmodified MSCs can exert antitumorigenic activity, and preliminary reports in immunocompetent animals have provided encouraging results for the use of MSCs in cancer immunotherapy. This review highlights recent works and potential clinical applications of MSCs in this field.

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Forced and maintained expression of four transcription factors OCT4, SOX2, KLF4 and c-MYC (OSKM), can reprogram somatic cells into induced Pluripotent Stem Cells (iPSCs) and a limited OSKM induction is able to rejuvenate the cell physiology without changing the cell identity. We therefore sought to determine if a burst of OSKM might improve tissue fitness and delay age-related pathologies in a whole animal. For this, we used a sensitive model of heterozygous premature aging mice carrying just one mutated Lamin A allele producing progerin. We briefly treated two months-young heterozygotes mice with OSKM and monitored their natural age-related deterioration by various health parameters. Surprisingly, a single two and a half weeks reprogramming was sufficient to improve body composition and functional capacities, over the entire lifespan. Mice treated early in life had improved tissue structures in bone, lung, spleen, kidney and skin, with an increased lifespan of 15%, associated to a differential DNA methylation signature. Altogether, our results indicate that a single short reprogramming early in life might initiate and propagate an epigenetically related rejuvenated cell physiology, to promote a healthy lifespan.