Spare parts: Healthy bone and cartilage

Thanks to an astounding new Israeli advance in regenerative medicine, science fiction is rapidly becoming reality. An Israeli company named Bonus BioGroup is only a few short years away from producing customized human bones from fat cells.

Researchers in other parts of the world have only published theoretical journal articles on the subject, but it took local minds to actually accomplish this feat.

The first to achieve the breakthrough, the Haifa company will face huge demand for living, healthy bone – grown according to patented technology – for surgical transplantation.

As that is accomplished clinically, and the technology receives official approval from the US Food and Drug Administration and other authorities, cartilage will be produced by the same process for more exciting applications.

Bonus Biogroup has already proven the success of its concept by removing human fat cells, isolating adult stem cells, inserting them into a three-dimensional scaffold and growing them into tiny but fully formed bones, which were then inserted into the legs of hairless mice.

Dr. Shai Meretzki, who earned degrees in biology, biotechnology and chemical engineering at Haifa’s Technion-Israel Institute of Technology and Rehovot’s Weizmann Institute of Science, is the company’s founder and CEO. An officer in the Israel Defense Forces’ armored corps, in civilian life he established a company named Pluristem (2001), based on his doctoral work, to grow cells in three dimensions.

It eventually became a $200 million public company traded on the stock exchange.

“There’s a big difference between a biologist and an engineer, which I am. It’s more practical, and you learn how to make things,” he said. “It will mean a world revolution in medical care,” he predicted.

Pluristem made use of stem cell patents he had developed with his colleagues in Rehovot, and the company was purchased by a local software company and changed its name to Pluristem Life Systems and then to Pluristem Therapeutics Inc., whose shares are traded on the NASDAQ exchange, the Tel Aviv Stock Exchange and the Frankfurt Stock Exchange.

The firm develops human placental cells for commercial use in disease treatment; patients with bone marrow disease have already been shown to improve significantly as a result of treatment. Meretzki later left the company, which continues to exist.

He refocused from working with single cells to whole tissues.

“At Bonus BioGroup, which I established in 2008, I work now with mesenchymal stem cells (MSCs), which are multipotent stromal cells that can differentiate into a variety of cell types. I took a monolayer of cells and developed a way to grow them in multilayer tissue, so that biologically and chemically, the cells are more like what happens in body,” he told The Jerusalem Post in an interview.

HIS NEW company with the strange name (based on “bone” and preferred by the stockholders) is a product-focused biotechnology firm applying patented technology for supplying bone and cartilage regeneration tissues. It is located just a few minutes’ drive from Meretzki’s alma mater, the Technion, and a minutes’ walk from Pluristem. Bonus BioGroup has a few dozen employees, most of them PhDs in biology, biotechnology and chemistry and physicians with joint MD/PhD degrees.

Its technology, with a multi-billion- dollar market, is sure to be pursued by patients around the world who have suffered bone loss due to cancer, road accidents and other physical trauma, osteoporosis, arthritis, hip fractures, knee injuries and more.

At present, doctors usually take autologous (“from self”) bone in parts of the leg (people can walk without having both the tibia and the fibula). Autologous bone grafting is the current gold standard in bone reconstitution field accounting for most bone reconstructions performed.

But this procedure has severe major handicaps. In many cases, there is not enough bone for the graft to be effective, in others, patients’ condition may decline. Patients can suffer from serious pain and discomfort or have problems getting about. In addition, the autologous bone grafts cannot be accurately shaped, negatively impacting the healing process and leaving ugly holes in the treated patients.

Thus “autologous grafts can be very difficult and painful,” said Meretzki, who added that there’s also the much-rarer “harvesting” of dead bone from cadavers. “This involves taking a supportive scaffold, not live tissue. And if taken from someone else, the donated bone causes the immune system to reject foreign tissue,” which requires medications to fight.

Thus finding a way for healthy new bone to be produced from the patient’s own fat cells creates a large supply and eliminates rejection.

The engineered bones create themselves, with interior channels for the blood vessels.

FOR SEVERAL years, Meretzki has been working with physicians at Assaf Harofeh Medical Center in Tzrifin and Emek Medical Center in Afula, which will be the first to perform clinical trials, implanting the engineered bones into patients.

Eventually, it will become available in hospitals throughout the world, with six or seven Bonus BioGroup centers around the world to provide bones for surgical procedures.

“It will be even cheaper than surgery moving bone from one part of the body to another or implanted donated bone,” Meretzki asserted.

“And surgeons will not have to learn new operating techniques; the surgery is just using a new source of bone or cartilage.”

With the development of computerized 3-D printing machines to create new objects, the biodegradable scaffold into which the cells are squeezed can be given the exact size and shape of a human bone; a few weeks later, after a bio-reactor grows the bone, the patient will be invited to come in and have his surgery and then be sent home. It will look like any other of his bones, as the scaffold disintegrates as the new bone grows.

“Our technology makes it possible to produce matched bone tissue in the precise, pre-designed architecture.

This leads to bone transplant available on demand, that fits like a tailored suit and is safer and less expensive,” Meretzi said.

“We are waiting for Helsinki Committee approval for human trials.

Since it is autologous, it won’t be very difficult to get, because the tissue comes from the patient’s own body. We will start with about 20 participants, who after the liposuction procedure carried out on an outpatient basis to remove fat cells wouldn’t have to be hospitalized,” Meretzki added.

“After a year or two of human trials, I believe we will be able to go ahead. The world bone-loss market is at least $3 billion. When we go on to produce healthy cartilage from the same patient’s fat cells, just think how we’ll be able to treat knees and other destroyed joints. The possibilities are endless. It will be good not only for Israelis here for also for the country’s medical tourism industry.”

He is also certain that many young physicians who want to learn a specialty will be eager to study surgery to make a place for themselves in a highly promising and exciting field.

PROF. NIMROD Rozen, head of Emek Medical Center’s orthopedics department, told The Post that he has been hugely impressed by Meretzki and his “brilliant” technology.

“Many of our hospital departments will be able to repair damaged bones and replace missing ones,” said Rozen, who was so certain about the efficacy of the breakthrough that he became a shareholder of Bonus BioGroup.

Dr. Ephraim Tzur, chief of oral and maxillofacial surgery department at the Tzrifin hospital, envisions lessconventional uses for the plentiful bone.

“We could use it to build fingers destroyed in work accidents. Later, we could create longer bones to make dwarves taller.”

Tzur added that oral and maxillofacial surgeons – but not dentists – could create pieces to augment the lower jaw by filling out the jawbone.

“This has been almost impossible until now. If they didn’t have 10 mm or so of bone, tooth implants were closed to them. There are patients with so little bone tissue in their jaw that they couldn’t benefit from tooth implants. It could also be added after the removal of cysts. There are also esthetic surgical applications, such as to adding bone to eye sockets so people can look younger.

“But of course, treating victims of cancer, road accidents, bullet wounds and even rock-throwing is more important,” he stressed. A fractured bone around the eye can be fixed and have a very pleasant result. Broken skulls with missing bone have for years been fixed with pieces of plastic. Now they can have real bone to replace it, literally leaving them without a hole in their heads.

Thus the Tzrifin surgeon is keen on completing his team’s research.

A world short of human bone will beat a path to Meretzki’s door.