Citrus surprise: Vitamin C boosts the reprogramming of adult cells into stem cells

December 24, 2009

Famous for its antioxidant properties and role in tissue repair, vitamin C is touted as beneficial for illnesses ranging from the common cold to cancer and perhaps even for slowing the aging process. Now, a study published online on December 24th by Cell Press in the journal Cell Stem Cell uncovers an unexpected new role for this natural compound: facilitating the generation of embryonic-like stem cells from adult cells.

Over the past few years, we have learned that adult cells can be reprogrammed into cells with characteristics similar to embryonic stem cells by turning on a select set of genes. Although the reprogrammed cells, called induced pluripotent stem cells (iPSCs), have tremendous potential for regenerative medicine, the conversion is extremely inefficient.

"The low efficiency of the reprogramming process has hampered progress with this technology and is indicative of how little we understand it. Further, this process is most challenging in human cells, raising a significant barrier for producing iPSCs and serious concerns about the quality of the cells that are generated," explains senior study author Dr. Duanqing Pei from the South China Institute for Stem Cell Biology and Regenerative Medicine at the Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences.

Dr. Pei and colleagues measured the production of reactive oxygen species or ROS during reprogramming and discovered a potential link between high ROS and low reprogramming efficiency. They became particularly interested in antioxidants, hypothesizing that they might suppress ROS and cell senescence, which seems to be a major roadblock for the generation of iPSCs.

The researchers found that adding vitamin C, an essential nutrient that is abundant in citrus fruits, enhanced iPSC generation from both mouse and human cells. Vitamin C accelerated gene expression changes and promoted a more efficient transition to the fully reprogrammed state. Somewhat to their surprise, they found that other antioxidants do not have the same effect, but vitamin C does seem to act at least in part through slowing cell senescence.

"Our results highlight a simple way to improve iPSC generation and provide additional insight into the mechanistic basis of reprogramming," concludes Dr. Pei. "It is also of interest that a vitamin with long-suspected anti-aging effects has such a potent influence on reprogramming, which can be considered a reversal of the aging process at the cellular level. It is likely that our work may stimulate further research in this area as well."
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The researchers include Miguel Angel Esteban, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Tao Wang, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Baoming Qin, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Jiayin Yang, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Dajiang Qin, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Jinglei Cai, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Wen Li1, Zhihui Weng, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Su Ni, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Keshi Chen, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Yuan Li, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Xiaopeng Liu, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Jianyong Xu, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Shiqiang Zhang, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Feng Li, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Wenzhi He1, Krystyna Labuda, Ludwig Boltzmann Institute for Clinical and Experimental Traumatology, Vienna, Austria, Austrian Cluster for Tissue Regeneration, Vienna, Austria, Yancheng Song, Austrian Cluster for Tissue Regeneration, Vienna, Austria; Anja Peterbauer, Austrian Cluster for Tissue Regeneration, Vienna, Austria, Red Cross Blood Transfusion Service of Upper Austria, Linz, Austria; Susanne Wolbank, Ludwig Boltzmann Institute for Clinical and Experimental Traumatology, Vienna, Austria, Austrian Cluster for Tissue Regeneration, Vienna, Austria, Heinz Redl, Ludwig Boltzmann Institute for Clinical and Experimental Traumatology, Vienna, Austria, Austrian Cluster for Tissue Regeneration, Vienna, Austria, Daozhang Cai, Austrian Cluster for Tissue Regeneration, Vienna, Austria; Lingwen Zeng, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; and Duanqing Pei, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.

Cell Press

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