Stem Cells

Induced pluripotent stem cells (iPS cells or iPSCs) are stem cells created from mature cells of the body, such as skin cells. These stem cells can then be directed to mature into a desired cell type. Scientists hope to use iPS cells to help repair damaged tissues and organs.

In 2013, researchers at the Center for Biosystems Dynamics Research (BDR) initiated the world’s first clinical study using iPS cells in human patients. The treatment was for age-related macular degeneration—a leading cause of vision loss in older people. In 2014, Masayo Takahashi and her collaborators performed the first transplant of iPS-cell derived laboratory grown tissue into a human patient. This initial effort used autogenic iPS cells, meaning that they were derived from the same person who received the transplant. Since then, the group has made further advances using animal models. In 2017, they showed that mice who received iPS cell-derived retinal transplants could see light and use the visual experience to modify their behavior.

In 2016, the group began allogenic iPS-cell transplants in monkeys. They grew retinal pigment epithelial cells from iPS cells derived from one monkey and succeeded in transplanting them into another monkey without rejection.

Based on this success, in February of 2017, the team launched a clinical research project using allogenic iPS cells (see image on left). This study is investigating the safety of transplanting retinal pigment epithelial cells generated from healthy donor-derived iPS cells into immune-type matched patients with age-related macular degeneration. The team has completed transplantation surgery in five patients as planned and is currently closely monitoring the patients for a one-year period.

Regenerative medicine

Other RIKEN laboratories are leading the way towards growing different types of human tissue and organs in the laboratory. In 2016, BDR scientists reprogrammed iPS cells and successfully grew complex skin tissue—complete with hair follicles and sebaceous glands—in the laboratory. They were then able to implant these tissues into living mice, and the tissues formed proper connections with other organ systems such as nerves and muscle fibers (see image on right). In the future, this technique could be used for functional skin transplants in burn victims and other patients who require new skin, or even to combat hair loss. Importantly, the lab-grown skin exhibited sustainable hair cycles, indicating functional regeneration.

Over the last two years, the team has developed a new method for mass producing regenerated hair follicles. In 2018, animal testing of hair follicle regeneration began in conjunction with the RIKEN Program for Drug Discovery and Medical Technology Platforms, which as part of the Cluster for Science, Technology, and Innovation Hub, has bridged the gap between basic research and partners within industry.

These first steps toward creating living 3D tissue in the laboratory are truly groundbreaking. RIKEN is leading the way in this field that was considered science fiction just a few years ago, and which could ultimately create a world in which injured tissues are commonly replaced with tissue grown outside the body.

iPS cells can also be used to study disease development. In 2016, BDR scientists used iPS cells derived from patients with spinocerebellar ataxia, and grew three-dimensional mature Purkinje cells. They found that patient-derived cells became vulnerable when deprived of thyroid hormone. This new model system can be used to develop drug therapies for genetic disorders.