Lest We Forget–‘Israeli stem cells could save the world from a nuclear health disaster’

Pluristem’s off-the-shelf placenta-based cell therapies are being tested by a top US agency – just in case

Times of Israel, Oct. 27, 2014

In the event of a nuclear catastrophe in the US, Israeli technology will stand ready to save millions of lives. Haifa-based Pluristem Therapeutics has been working for the past eight months with the US National Institutes of Health on developing a treatment for acute radiation syndrome (ARS) – the mass destruction of tissues and cells caused by exposure to high levels of radiation, like from a bomb or a nuclear accident.

In tests conducted in Israel and the US, animals, most of them mice, were subjected to total-body irradiation, then injected with human cytokines. They showed significantly increased survival rates when treated with Pluristem’s PLX-RAD cells. The treatment actually reversed the effects of radiation disease to a great extent, a development once thought impossible.

The reversal is just one of the near-miraculous things that Pluristem’s technology is capable of, said Zami Aberman, chairman and CEO. It’s based on harvesting cells from human placenta. On a special tour of ‘the cleanest room in Israel’ — a highly secure area where bioreactors ‘cook up’ therapeutic cell products using human placental cells harvested from donated placentas – Aberman described the benefits of using what until just a few years ago had been considered ‘dead waste’ by scientists.

‘I come from an engineering background, not a medical background, so maybe that’s why I was less hesitant to go ahead with placenta-based cell development,’ said Aberman. ‘Everyone said it couldn’t be done, but they were wrong, obviously.’

While there are many companies today harvesting human cells, like stem cells, to develop therapeutic products, Pluristem was the first and still one of the only companies doing that by harvesting from placenta. ‘Usually, you need a genetic match, or at least tissue compatibility, in order to use cells for therapeutic purposes,’ Aberman said. ‘As we know from organ transplants, the body often rejects outside material. But placenta is the only place in nature where an outside organism – a fetus – is able to co-exist with the body without triggering a reaction,’ like the release of antibodies. Placenta is the point of connection between mother and fetus, and thus, logically, would be the material that was most ‘tolerant.’

That was the theory in 2006, when the company was first established, and the theory had been confirmed many times over. Over the past several years, animal placenta, especially from horses, has been used by alternative physicians to treat sports injuries. Placenta, according to researchers, enhances cell repair and speeds up the healing process significantly. Using human placenta because it is more compatible with the human genome, Pluristem processes and enhances the cells, using proprietary methods inside a bioreactor created by the company. The result, said Aberman, is ‘a drug delivery platform that releases a cocktail of therapeutic proteins in response to a host of local and systemic inflammatory and ischemic diseases.’

Perhaps the most important aspect of Pluristem’s technology is what could be called its ‘business side.’ Instead of manufacturing cells for specific purposes, the company creates ‘generic’ cells, an ‘off-the-shelf’ product that can later be processed for whatever is needed. The cells, stored in deep freeze (minus 200 degrees Celsius), have a shelf life of at least two years. Aberman believes they could last even longer. Pluristem creates what Aberman calls a 3D micro-environment that matches the ‘challenging and cultures conditions’ of a specific health issue – such as conditions for an injury, arteriosclerosis, or massive cell injury due to radiation sickness – and the placenta-based cells adjust themselves to the conditions, and significantly enhance the repair process, he said.

How does it work? According to Pluristem researchers, the placenta contains mesenchymal-like adherent stromal cells, which have been found by researchers to have significant therapeutic potential. The cells promote tissue repair, possibly by secreting biologically active substances, including cytokines, that modulate immune response, along with factors that enhance the growth of blood vessels. These cells stimulate the body’s own mechanisms to heal damaged tissues. Because placental cells themselves are immune privileged, meaning that they do not elicit an immunological response from the body, as other cells do, they can be used freely for any purpose without requiring tissue matching.

Pluristem ‘harvests’ the placenta from a hospital in northern Israel, where it is donated by women undergoing caesarean section births. The births are planned in advance, allowing the company to set up the equipment needed to ensure that the placenta is still living and not contaminated by the environment. It is then rushed to Pluristem’s facility, where it is processed into PLX (PLacental eXpanded) cells, for use in a variety of applications.

The company has conducted dozens of tests showing the efficacy of its solution – including several on animals that showed a significant improvement in cases of radiation sickness. According to one of the studies, mice showed a four-fold increase in their survival rate, accompanied by a corresponding weight regain, and a large increase in blood cell count when treated with Pluristem PLX cells. Other tests have shown how injuries to limbs repair themselves much faster, even among individuals with severe injuries, arteriosclerosis, and other serious conditions.

The US National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health (NIH), has been conducting its own study on how Pluristem’s technology could be useful to humans in the event of mass nuclear destruction. According to Aberman, the agency has been very positive about the results, to the extent that along with Pluristem, it has already developed a plan for the creation, delivery, and deployment of millions of doses of PLX-based radiation treatments.

Radiation sickness induces a wide variety of health effects that occur within several days to months after exposure to high doses of ionizing radiation from a nuclear event, such as a nuclear power plant accident. Especially affected is bone marrow. Its deterioration leads to severe anemia, hemorrhages and failure of the immune system. PLX cells can handle bone marrow issues as well, said Prof. Raphael Gorodetsky, lead investigator of the study and head of the Biotechnology and Radiobiology Laboratory at the Sharett Institute of Oncology at Hadassah, Hebrew University Medical Center, where several of the Pluristem tests have taken place.

‘Following preclinical studies using Pluristem’s placental derived cells, we found that these placenta cells have the ability to potentially increase the survival rate of animals following exposure to lethal doses of total body irradiation,’ he said. ‘The higher survival rate of the PLX treated animals, compared to the control group, is accompanied with better hematological profile, as reflected by the increase of all the cell lines of the hematopoietic system and in the blood hemoglobin levels. These findings substantially strengthen the hypothesis that Pluristem’s placenta-derived cells could potentially be used to reduce complications associated with life threatening ARS.’

Why stop at radiation disease? Aberman said the company does not intend to. Pluristem’s development plan for the PLX-RAD cells considers numerous potential clinical indications such as enhancement of engraftment of transplanted hematopoietic stem cells for the treatment of bone marrow deficiency, which can result from immune system disorders, genetic diseases, and treatment of leukemia and other blood cancers, as well as treatment of bone marrow deficiency in patients who have undergone chemotherapy.

‘We’ve just completed a two-year development cycle for our PLX-RAD cells and have also developed new manufacturing equipment, methods and know-how. We believe that our state-of-the-art technology platform can be used to create additional cell products from the placenta, tailored to potentially deliver targeted treatments for a variety of new indications,’ said Aberman. ‘Our technology platform, robust manufacturing capabilities and broad IP portfolio open the door for potential institutional and commercial partners, and we’re pleased with the level of interest we have received in our technology platform. Pluristem is in a unique position to be a leader in the cell therapy industry.’