Earticle

The purpose of this lecture is to overview the current cellular products and their manufacturing process. Recently, stem cell therapies are considered to be a promising platform for cell and gene therapy for a variety of diseases. However, maintenance of the multipotency and self-renewal expansion of stem cells in vitro are the most difficult operations and essential factors for the clinical application of the stem cells into various patients. Unlike the production of biopharmaceuticals, the cultivation process of stem cells is relevant to the design of bioreactors. Because final products are not proteins but stem cells, accurate characterization of the final products should be performed and also regulatory systems of the cultivation should be developed. After all, novel bioreactors will be needed for the consistent production of stem cells with multidisciplinary systems.

Hypoxic culture is widely recognized as a method to efficiently expand human mesenchymal stem cells (MSCs) without loss of stem cell properties. However, the molecular basis of how hypoxia priming benefits MSC expansion remains unclear. In this report, our systemic quantitative proteomic and RT-PCR analyses revealed the involvement of hypoxic conditioning activated genes in the signaling process of the mitotic cell cycle. Introduction of screened two mitotic cyclins, CCNA2 and CCNB1, significantly extended the proliferation lifespan of MSCs in normoxic condition. Our results provide important molecular evidence that multipotency of human MSCs by hypoxic conditioning is determined by the mitotic cell cycle duration. Thus, the activation of mitotic cyclins could be a potential strategy to the application of stem cell therapy.