Waddington’s epigenetic landscape is well-known for cell fate, according to Masahiro Kino-oka, PhD, professor in the department of biotechnology and director in the research base for cell manufacturability at Osaka University in Japan. In the mid-1950s, the late British scientist Conrad Hal Waddington depicted cellular development as hills and valleys—a landscape—that cells travel toward differentiation. Kino-oka applies that concept to the culture properties for stem-cell differentiation.

The process of differentiation in induced pluripotent stem cells (iPSCs) depends on various factors. As examples, Kino-oka points out mechanotransduction and the level of methylation. “Epigenic memory—the level of methylation—occurs in culture through the specific mechanotransduction, causing the quality fluctuation in the culture process of stem cells,” he says.

By thinking of iPSC bioprocessing following Waddington’s epigenetic landscape, Kino-oka says, “We have to consider the process stability due to easy fluctuation of cell quality.” That’s not easy to control. “The major trigger against the instability is considered to be methylation through mechanotransduction,” Kino-oka explains.

Although Waddington’s idea is not new, Kino-oka envisions unique advances in iPSC bioprocessing by using this concept. “We believe two concepts—cell manufacturability and Waddington’s epigenetic landscape—can be merged to realize the stability of the process for the production of stem cells,” he says.

Kino-oka has already developed a manufacturing plan based on this thinking. He says, “The design for cell manufacturability will lead to the process stability.” With the growing interest in cell-based therapies, the bioprocessing industry needs ways to control the differentiation and create homogeneous cultures. That’s just the kind of new iPSC-bioprocessing landscape that Kino-oka hopes to create.

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