Not long after fertilisation, the embryo consists of a tiny sphere of identical, non-specialised cells, referred to as pluripotent stem cells. These have the ability to stay in this state indefinitely, while dividing to produce daughter cells that are capable of turning into any cell type found in the adult body. These embryonic stem cells offered hope for researchers trying to develop disease treatments, but the fact that they could only be obtained from human embryos raised serious ethical questions about their use.

Then, in 2007, a team led by Shinya Yamanaka of Kyoto University demonstrated that connective tissue cells from adult rats could be made to revert to a pluripotent, stem cell-like state and reprogrammed to form different cell types. Others went on to show that cells taken from just about anywhere in the human body can be similarly reprogrammed, into just about any other type of cell.

By 2008, US researchers had taken skin cells from an 82-year-old woman with amyotrophic lateral sclerosis (ALS, a form of motor neuron disease), placed them into petri dishes and reprogrammed them to form the same motor neurons that are destroyed by the disease. By 2010, researchers at Stanford had shown that mouse connective tissue cells could be reprogrammed directly into neurons, bypassing the pluripotent state.

These advances provided a new – and less controversial – way of obtaining human embryonic stem cells. Researchers could grow them in the lab and reprogramme them however they wished, to study the molecular and cellular mechanisms of diseases and to test the effects of newly developed drugs. They also made possible a milestone in regenerative medicine: the first successful transplant of an organ grown entirely from man-made tissue.

The recipient was Andemariam Teklesenbet Beyene, a 36-year-old Eritrean man who was studying for a Master’s in geophysics at the University of Iceland. During his studies, Beyene was diagnosed with advanced cancer, then developed a golf ball-sized tumour that blocked his windpipe. He initially refused the revolutionary treatment that was offered to him, but he agreed after consulting with his doctor in Iceland and his family.

The treatment required the coordinated activity of three teams, each in a different part of the world. First, computerised tomography scans of Beyene’s windpipe were sent to researchers at UCL. They used the scans to build a Y-shaped glass mould, which was coated with a nanocomposite polymer to form a porous scaffold. This scaffold was sent to the USA and Harvard Bioscience, who ‘seeded’ the scaffold with stem cells taken from Beyene’s bone marrow, then incubated it in a specially designed bioreactor for several days; this allowed the cells to infiltrate the pores in the scaffold and to differentiate to form connective tissue. Finally, the scaffold was sent to the Karolinska Institute in Stockholm, where the 12-hour transplant operation took place.

Paolo Macchiarini, a surgeon at the Karolinska Institute, and his colleagues successfully transplanted the first completely synthetic windpipe in June 2011. Beyene remained weak and bedridden for several weeks after the procedure, but he eventually recovered and graduated from university about eight months later.

Windpipe transplants had been performed before but had all involved real windpipes from human donors, stripped down to the cartilage and repopulated with the recipients’ stem cells. Finding a suitable donor can take months, so the use of an artificial scaffold dramatically shortens the time needed. For Beyene, this was life-saving. (It also overcomes another obstacle: because Beyene’s new windpipe is completely synthetic, his body is far less likely to reject it, so he doesn’t need to take the powerful immune-suppressant drugs that other transplant patients take to stop this from happening.)

Tens of thousands of people worldwide are waiting for organ transplants, but there aren’t enough organs to go around – last year, more than 5,600 people were on the waiting list for a kidney transplant in the UK, but just over 3,000 received one. The global shortage of donors has fuelled a lucrative and growing black market: kidneys harvested from living donors can be sold for more than $30,000 and will soon outnumber those taken from the dead.

“Our ultimate goal is to help address the shortage of donor organs available for transplant and to develop therapies for diseases,” says Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine in North Carolina, USA. “I foresee the field advancing so that treatments are gradually developed for a wider range of conditions.”

Atala and his colleagues have used scaffolds to grow bladders, urethras and, most recently, vaginas from patients’ own cells, and have shown that they remain safe and effective for years after transplantation. “We’re now conducting a clinical trial evaluating the safety of muscle progenitor cells for the treatment of urinary incontinence in women,” says Atala, “and we have a variety of projects that aren’t at the trial stage yet, including printing skin cells onto burn wounds and cell therapies for kidney disease, cystic fibrosis and haemophilia.”

Back in Kobe, the Laboratory for Organogenesis and Neurogenesis is growing tissues and organs using an altogether different approach, which doesn’t use scaffolds. Remarkably, they have found that embryonic stem cells can organise themselves into highly complex three-dimensional structures when guided in the right direction. Using a specially developed technique, the team has already coaxed embryonic stem cells to become partial pituitary glands and even bits of brains. Their greatest achievement to date is growing partial embryonic eyes, complete with retinal tissue containing light-sensitive cells, in the hope of developing a new stem cell-based treatment for various diseases that cause blindness.

“We really don’t know where we are going with this,” Yoshiki Sasai, the then director of the lab and Deputy Director of the CDB, told me. “We really are at the final frontier, facing an unknown world.”