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Induced Pluripotent Stem Cells: 10 Years After the Breakthrough

Human cortex grown in a petri dish. Eye diseases treated with retinal cells derived from a patient’s own skin cells. New drugs tested on human cells instead of animal models.

Research and emerging treatments with stem cells today can be traced to a startling discovery 10 years ago when Shinya Yamanaka, MD, PhD, and his graduate student Kazutoshi Takahashi, PhD, reported a way to reprogram adult mouse cells and coax them back to their embryonic state – pluripotent stem cells.

A year later, they accomplished the feat with human cells. For this research coup and his leading role pioneering stem cell work, Yamanaka – who holds academic appointments at Kyoto University and UC San Francisco – was the co-recipient of the 2012 Nobel Prize in Medicine or Physiology.

The breakthrough provides a limitless supply of induced pluripotent stem cells (iPSCs) that can then be directed down any developmental path to generate specific types of adult cells, from skin to heart to neuron, for use in basic research, drug discovery and treating disease.

The achievement opened up a practical way – and in some critical cases, the only way to directly study human “diseases in a dish,” and track the early stages of both healthy and abnormal development. It also allowed researchers to screen new drugs directly in human cells rather than relying on animal models, which more often than not fail to accurately predict a new drug’s effects on people.

The dazzling iPSC breakthrough has spurred rapid progress in some areas and posed major challenges in others. It has already proved a boon to basic research, but applying the new technology to treat diseases remains daunting. Some types of cells have proved difficult to reprogram, and even the protocols for doing so are still in flux as this is still a very young field.

iPSCs in Basic Biomedical Research

For many basic biomedical scientists, the capability offered by iPSCs technology is like a dream come true, says neuroscientist Arnold Kriegstein, MD, PhD, director of UCSF’s Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research.

“Induced pluripotent stem cells have given us a window into human development unlike anything we had before,” Kriegstein said. “I’m interested in the early development of the brain’s cortex. Of course, we’ve never had unrestricted access to living human brain cells. Now we can take skin cells and grow human cortex in a dish. It’s a game-changer for discovery about early human development.”

Kriegstein is enthusiastic about what researchers can learn from “organoids” – a pea-sized stage of a developing organ derived from iPSCs. By this stage, cells are already clumping together and starting to signal and differentiate into what will become the adult organ.

“It’s a very close model of the real thing,” Kriegstein says. “We have recently discovered that even in this early stage, the organoids are able to develop intrinsic organization, including a front-and-back orientation, and different parts start to look like they do in the embryonic brain.”

Some scientific papers have suggested that organoids can model diseases found in adulthood – even disorders of late adulthood such as Alzheimer’s disease.



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