Stem-cell Research Is Blooming in Israel

Next week, 18 cutting-edge Israeli companies will mingle with peers from around the world at the Israstem Conference in Ramat Gan.

At a massive scientific parley next week, 18 Israeli companies and several more from around the world will meet to discuss stem cells, cell therapy, and regenerative medicine in both industry and academia.

Use of human cells to treat disease has expanded dramatically over the past decade, leading to the development of a new field: cell therapy — or, in professional terms, regenerative medicine. It involves introducing cells into the body to replace diseased or dying cells with healthy ones.

Over the past few years, the knowledge accumulated in the field has begun to leave the laboratories of academia for the commercial world, the development of innovative treatments in hospitals and even the production of off-the-shelf products. In Israel, 18 companies — an unprecedentedly large proportion in relation to the country’s population — develop or market cell-based treatment products. Three of them develop therapies from stem cells produced from early embryos (human embryonic stem cells). All of these will be on hand at the Israstem Conference next week (April 22 and 23) at the Kfar Maccabiah Convention and Event Center in Ramat Gan.

So far, health services in Western countries have approved five off-the-shelf products based on cells from various sources. Additional products are in the pipeline. One product developed in Israel by Pluristem Therapeutics uses mesenchymal stem cells isolated from human placenta to treat peripheral blood disease, prevent limb amputations and improve patient life expectancy. Mesenchymal stem cells can be isloated from various tissues such as fat, bone marrow, cord blood, and placenta. These cells produce many proteins that can stimulate growth of damaged tissues.

Some cell-therapy products are not off-the-shelf. Rather, they are treatments that allow the use of the patient’s own cells after they have undergone a process of activation outside the body. For example, Dendreon, an American biotechnology company that focuses on cancer, is developing a vaccine against prostate cancer that uses the patient’s own blood cells, mixed with the company’s proprietary technology.

Dr. Shosh Merchav, the former head of the Cell Therapy Projects Unit at Teva Innovative Ventures and now a private consultant in the stem-cell industry, is co-chair of the Israstem Conference.

“The model on which such products are based is different from off-the-shelf products," she says. "Of course, at the business level, off-the-shelf products have an advantage because the cells that have been produced can be preserved for longer and used for any patient, not just for the patient from whom they were harvested.”

A product based on treating patients with activated cells that has already been approved in Israel and added to the list of treatments provided by the Health Ministry was developed by the Israeli company MacroCure, which uses cells from the blood donations of healthy people. White blood cells from the donated blood that undergo activation via a specific technology are used to treat particularly stubborn wounds. “These cells stimulate a response from the patient’s own cells, including skin cells and white blood cells, to encourage wound healing,” says Dr. Avi Treves, chairman of the Israstem Conference and the deputy director of the Sheba Cancer Research Center at the Sheba Medical Center.

Of the 18 Israeli companies in the field, nine develop or produce products that come from donors other than the patients, eight develop treatments from the cells of the patients themselves, and one company is in the first stages of safety trials for a new product made from the cartilage cells of miniature pigs.

Gamida Cell, a cell therapy company, is awaiting approval from the United States Food and Drug Administration for a treatment that uses umbilical-cord-derived stem cells expanded with the company’s proprietary technology to treat adult leukemia patients. “Umbilical cord contains stem cells that come from the fetuses. These cells are already used routinely to treat patients with leukemia as an alternative to bone-marrow transplants," Treves says. "The new product allows the multiplication of these cells, producing a larger dose that can increase the chances of success.”

Several products that use the patient's own cells are already in clinical trials. A product made by the Israeli company BrainStorm Cell Therapeutics, which uses cells from the patient's own bone marrow to treat Amyotrophic Lateral Sclerosis (ALS, also known as Lou Gehrig’s Disease), is being tested at Hadassah University Hospital, Ein Kerem. A technology for treating autism with the patient’s own umbilical-cord blood is being developed in the United States, as is another treatment of cerebral palsy that uses the patient’s own umbilical-cord blood.

At Sheba Medical Center, stem-cell-based therapies are being developed to treat hard-to-heal wounds and retinitis pigmentosa, an eye disease that attacks the retina and can lead to blindness. A presentation will also be given at the conference on the positive results of an ongoing study at the Ella Institute for Treatment and Research of Melanoma and Skin Cancer at the Sheba Medical Center. The treatment being studied is based on the activation of immune cells outside the body and their introduction into melanoma patients together with new anti-cancer treatments. The findings, from more than 50 patients, show a high rate of efficacy.

Additional findings that will be presented at the conference include those of a study by Zelig Eshhar of the Weizmann Institute of Science, which is still in the academic stage. Eshhar is developing an advanced technology that uses genetically-engineered T cells, called chimeric antigen receptor (CAR) cells, to teach a person’s immune system to destroy a specific cancer. The technology uses the patient’s own white blood cells, which are activated by the injection of a specific gene, giving them the ability to identify, attack and kill the cancer cells. Human trials based on the technology are testing the efficacy of this therapy against several types of leukemia and glioblastoma, the most common and aggressive brain tumor in humans.

Another branch of the stem-cell therapy field that is still in early development is testing the advantages of treatments developed from embryonic stem cells — cells obtained from early embryos donated by couples undergoing the treatment. In the past, this method caused an ethical controversy in the U.S., and for several years during the Bush administration, government funding for these studies was stopped. It was later restored. Israel's scientists are pioneers in embryonic stem cell research, and three companies here develop stem-cell products from this source.

One goal of the Israstem conference is to stimulate government investment in Israel’s stem-cell therapy industry. “Many countries invest a great deal in the industry,” says Merchav.

Governmental investment in stem-cell therapy is minimal in Israel. In 2003, Israeli companies, together with the chief scientist of the Industry, Trade and Labor Ministry, established the Bereshit Consortium for Cell Therapy (Bereshit is the Hebrew word for “genesis”), a six-year funding program to speed up the development of cell therapies in Israel. For example, the consortium supported the development at Hadassah University Hospital, Ein Kerem of  lines of embryonic stem cells that can be used to assist in treating blindness caused by age-related macular degeneration (AMD). It closed in 2009 after six years of operation.

According to Merchav, “Without investment in the field, we will lose our advantage over countries such as the United States, Japan, South Korea, the United Kingdom and Australia, which lead in investments.”

Stem-cell therapy has also raised concerns regarding side effects. The side effect feared most is that the transplanted cells, which are “young” cells and have a tendency to grow quickly, could grow uncontrollably in the patient’s body, causing malignant tumors.

According to Dr. Treves: "All embryonic products being developed are subjected to extensive safety tests in the laboratory and on animals in order to rule out the risk of tumors developing before they are injected into the patient's body. Most of the reports regarding cancerous developments in cells that have been used for therapeutic purposes are anecdotal, and originate from unauthorized clinics, or from cells that have not passed the safety checks and quality control tests that are required before they are given to the patient."

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