Israeli placenta-derived cells get nod from top researchers
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Israeli placenta-derived cells get nod from top researchers

Pluristem’s platform, which delivers a ‘cocktail of therapeutic proteins,’ is seen to be useful for a slew of diseases

Pluristem workers process placenta for the company's cell-based therapy products (Courtesy)
Pluristem workers process placenta for the company's cell-based therapy products (Courtesy)

A new study on Israeli-developed stem cells developed by Israeli biotech Pluristem shows they could help patients suffering from a wide array of physical injuries to live longer and healthier lives.

Israeli biotech Pluristem’s off-the-shelf PLacental eXpanded (PLX) cells, derived from harvested human placenta, have already been shown to be effective in ensuring that transplanted organs are assimilated by the body and in reversing nerve damage, and even in helping individuals afflicted with radiation disease recover.

The study, conducted by scientists at the Berlin-Brandenburg Center for Regenerative Therapy at Charité – University Medicine Berlin, showed “how PLX cells and other mesenchymal stromal cells (MSC) influence the immune system in order to modulate immune reactions and to prevent immune reactions against the cells,” Pluristem said.

The study showed “in vitro that MSC, and in particular PLX cells, control the induction of an immune response at several points” – essentially allowing doctors to regulate the immune system, speeding it up or slowing it down as needed.

The Berlin-Brandenburg Center is considered one of the world’s most important centers for interdisciplinary study of materials and factors which can be used to develop and implement innovative therapies and products for cell regeneration.

PLX is a commercial product developed by Haifa-based Pluristem based on mesenchymal stromal cells – a type of stem cell that can be used for numerous purposes in the body. MSCs have in particular been shown to be effective in interfering with the function of T-cells and their dendritic cell companions.

But Pluristem uses not just any MSC version; PLX is derived from human placenta. Placenta, according to researchers, enhances cell repair, and speeds up the healing process signifcantly. 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.

While there are many companies today harvesting human cells – like stem cells – to develop therapeutic products, Pluristem was the first, and is still one of the only companies harvesting them from placenta. Placenta, according to researchers, enhances cell repair, and speeds up the healing process signifcantly. 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 Pluristem CEO Zami 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.”

According to Pluristem researchers, placenta contains MSCs, which 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. And, because placental cells themselves are immunoprivileged (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's first bioreactor for the enrichment of mesenchymal adherent stromal cells (ASCs) from cord blood (Photo credit: Courtesy)
Pluristem’s first bioreactor for the enrichment of mesenchymal adherent stromal cells (ASCs) from cord blood (Courtesy)

The Berlin-Brandenburg study focused on the dendritic cells, which are the key player in inducing a T-cell immune response. Dendritic cells basically tell the immune system to activate itself, issuing the T-cells that are used to ward off “invasion” of the body. In most cases, this is a good thing – but the body also responds in the same way to good invasions, like organ transplants and skin grafts.

According to the study, PLX was able to successfully regulate the activity of dendritic cells in patients suffering from critical limb ischemia (an obstruction of the arteries that prevents blood from reaching the extremities) who were treated with PLX cells in a phase I/II study. The current study confirmed that the PLX cells did not provoke an immune response when the patients were treated with them. “These findings confirm the feasibility of using PLX cells in an off-the-shelf manner, and explain the mechanisms that make this possible,” the report said. This was the one of the first studies that showed the MSCs, and specifically PLX, interacts with the immune system, said Aberman.

Previous tests of PLX have shown that they protect PC12 cells – rat-derived cells that behave similarly to, and are used as stand-ins to study human nerve cells. The study shows PLX cells protecting the PC12 cells from death after oxygen and glucose deprivation. Such deprivation, many scientific studies have shown, are an important factor in stroke – thus indicating that there is a good chance that PLX could prevent, or even reverse, the damage caused by stroke or other neuronal disease, Pluristem believes.

PLX will even come in handy in the event of a nuclear holocaust, studies show. The United States National Institutes of Health (NIH) has been testing a version of PLX to treat bone marrow damaged by exposure to high levels of radiation. Tests by the NIH showed that injection of PLX-R18 cells into muscle, as compared to a placebo, resulted in a “statistically significant improvement in the recovery of white blood cell, red blood cell, and platelet levels in animals exposed to high levels of radiation” – the three blood lineages that the body is unable to produce due to acute radiation syndrome (ARS), a condition caused by high-dose irradiation that can involve severe, sometimes lethal damage to the bone marrow as well as other physiologic systems and organs, Pluristem said.

“The data also suggested that the treatment may potentially be able to shorten time to recovery,” the company added.

“Our findings in this study provide novel evidence for the regulation of several checkpoints of T-cell priming by PLX cells and other MSC, via modulation of the crosstalk between myeloid dendritic cells and natural killer cells,” said the study’s chief examiner, Dr. Hans-Dieter Volk, Director of the Berlin-Brandenburg Center. “While the complete mechanism of immunomodulation by PLX cells requires further investigation, this study demonstrates how PLX cells might inhibit the immune responses of Type 1 T helper cell,” he added.

“The investigation of the interaction between unmatched PLX cells and patient immune systems is central to Pluristem’s clinical research. This research may lead to a new understanding of how PLX cells influence, and potentially heal, the immune system, thereby possibly expanding the use of PLX cells for new indications,” said Pluristem CEO Aberman. “By modulating a patient’s immune response, PLX cells could potentially help treat severe diseases of the immune system such as aplastic anemia, which has been designated as an orphan indication, autoimmune diseases such as multiple sclerosis and lupus, as well as graft versus host disease (GVHD).”

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