Waltham, MA. Minerva Biotechnologies, a leading cancer and stem cell development company today announced a major breakthrough in human stem cell research. Minerva scientists converted established human stem cells to the elusive “naïve” state and maintained them there indefinitely simply by culturing the cells in the dimeric form of a natural, but newly discovered human growth factor, called NM23-H1. It is widely believed that figuring out how to stably induce naïve pluripotency in human stem cells is critical for realizing the promise of human stem cell therapies.
“This is very exciting,” said Dr. Cynthia Bamdad, Minerva President and Chief Executive Officer, “Until now scientists had only been able to temporarily convert human stem cells to the naïve state by genetically modifying the cells or by treating the cells with a cocktail of biochemical inhibitors. This appears to be the natural growth factor that keeps stem cells in the truly pluripotent naïve state and overcomes what had been a major impediment to developing human stem cell therapies.”
Scientists have recently become quite interested in getting human stem cells into the “ground” or “naïve” state because only these cells are truly pluripotent and able to properly differentiate into any cell in the human body. Mouse stem cells have been much easier to work with because the growth factor that maintains them in the naïve state has been known for some time. However, the growth factor that maintains human stem cells in the naïve state was, until now, unknown. Cultured human stem cells exist in a more mature state, called “primed”. Thus, the numerous breakthroughs in mouse stem cell science simply cannot be reproduced using human stem cells. Therefore, it has been a major scientific goal to understand the biology of human stem cells: to understand what regulates naïve pluripotency and what induces their differentiation to the primed state.
In a research article, “MUC1* Ligand, NM23-H1, is a Novel Growth Factor that Maintains Human Stem Cells in a More Naïve State,” published today in the journal PLoS ONE, Minerva reported that, for the first time, generically unmodified human stem cells were converted to, and maintained in, the “naïve” state by culturing the cells in the dimeric form of a naturally occurring protein called NM23-H1. Interestingly, subsequent exposure of the naïve cells to bFGF, the standard growth factor used in all human stem cell culture, reversed the process and caused the cells to enter the “primed” state. As predicted by comparison to mouse naive cells, the NM23-H1 cultured stem cells had a much higher cloning efficiency than the same cells cultured in FGF-containing media and differentiated in a coordinated way with as high as 90% of the cells in a local environment differentiating down the same germline. The Minerva system is free of feeder cells, conditioned media, exogenously added cytokines or growth factors, other than NM23-H1. After initial acclimation to the new media, the stem cells remain essentially 100% pluripotent, requiring no manual dissection or other manipulations that would interfere with large scale production and automated stem cell culture.
Kenneth S. Kosik, M.D., the Harriman Professor of Neuroscience and Co-Director of the UC Santa Barbara Neuroscience Research Institute, as well as a co-author on the paper said, “The results reported today provide both basic insights into the biology of human stem cells and open the door to medical applications for stem cells.”