Adapted from an article by Assaf Levanon, in cooperation with the Organoid Center, Hadassah Hospital Ein Kerem
Organoids, three-dimensional cell cultures that replicate the tissues from which they are produced, offer researchers the reality of developing personalized medicine on a scale never before realized.
The Organoid Center at Hadassah Ein Kerem, the first of its kind in Israel, was established by Hadassah at the initiative of Prof. Eyal Mishani, head of Hadassah’s Research and Development Department and the Research Fund. The director of the center is Dr. Myriam Grunewald, a specialist in vascular biology. Serving as director of the center’s clinic is Dr. Liron Birimberg-Schwartz, a pediatric gastroenterologist.
Much of the center’s research efforts is focused on cancer. Despite the substantial progress in preventive medicine, early diagnosis and specific therapies for various types of malignancies, cancer remains one of the leading causes of death in the world, partly because existing pre-clinical models for cancer research do not reflect the disease in humans in a precise way.
Dr. Grunewald explains, “Cancer research in recent decades was based mainly on two-dimensional culture of cell lines, tumor models in genetically engineered mice, and human tumor models transplanted into mice with no immune systems.” But there are limits to the usefulness of the findings because, she continues, “Traditional cell cultures fail to preserve the characteristics of human tumors, and particularly their heterogeneity.”
“Organoids have the potential to overcome the limitations of the existing methods,” adds Dr. Birimberg-Schwartz. “The method of growing organoids was developed in the past decade on the basis of stem cells of intestinal tissue in the laboratory of Prof. Hans Clevers, under the leadership of Dr. Toshiro Sato. The researchers found a way to grow the stem cells in such a way that they keep their characteristics as stem cells, but at the same time they can divide and differentiate into all types of cells, just as in the original tissue.”
Prof. Tamar Peretz, a senior oncologist and cancer researcher at Hadassah, experienced frustration over the fact that despite the immense effort and enormous amounts of money invested in research, not all cancer patients could be helped, and the medical field had to content itself with prolonging their lives rather than curing them.
She reports, “One reason for that is the fact that tumors have many faces—in other words, they are heterogeneous. In one tumor that we removed, there are many subtypes of cancer, and many times we treat one type successfully but another subtype remains and continues to grow. Another problem is interaction with the environment. We understand that tumors do not grow in a vacuum; they are influenced greatly by the environment in which they live.”
Prof. Peretz sees the organoid model as a breakthrough. “A three-dimensional model that simulates the situation as it appears in the human body and deals with the possibilities of the micro-environment enables an examination of various types of tumors, and thus solves the problems.” It means that different drugs can be tried in the laboratory. As Dr. Birimberg-Schwartz explains, “Organoids that are produced from the tumor help in tailoring the most appropriate therapy to each cancer patient, a situation that will decrease the patients’ suffering and reduce the health-care system’s financial expenditures.”
The human tissue used to grow organoids is obtained by consent from patients undergoing biopsies or surgery. “It is important to note that the center has approval from the Helsinki Committee [the committee that supervises the ethics of research on human beings],” says Dr. Birimberg-Schwartz, “and that the patients receive a detailed explanation about the research before they sign the consent form.”
Dr. Mohammad Adileh, an oncological surgeon at Hadassah, explains how a tiny sample from a tumor can be used to create an almost limitless quantity of organoids. “A tiny piece of tumor tissue is removed from the patient’s body and taken to the laboratory once the pathologists give their approval. There begins the process of breaking the tissue down into tiny clusters that contain cancer cells. One of the unique things about organoids is that they grow in biological gel that enables them to arrange themselves in a three-dimensional manner. It’s amazing to see that the cells in the culture dish can arrange themselves just like they do in the body.” In a relatively short time, experiments can begin to determine the treatments most suitable for the patient personally.
“The ability of organoids to rejuvenate themselves on their own enables an expansion of the culture and the tumor for long periods of time. Organoids from a tumor source can be grown, frozen, and thawed almost infinitely. This means that there is an enormous advantage and ability to bridge the gaps that exist in other methods,” Dr. Grunewald says. Moreover, suitably frozen organoids can be sent to other centers around the world. In Israel, Hadassah is so far the only center to set up a database accessible to the entire scientific community in Israel. Biotech companies can use it to speed up drug development processes and check criteria for including patients in clinical trials. This method enables an efficient examination of new drugs and the repurposing of existing ones. It should be noted that the U.S. Food and Drug Administration approved the use of human organoids for effective proof of drugs that have already been approved for various types of cancer, helpful to cancer patients with rare or even unknown mutations.
“Our supreme goal,” Dr. Grunewald and Dr. Birimberg-Schwartz explain, “is that every medical center in Israel will have access to our system and that it will serve as a ‘treatment point’ in order to enable a prediction of the recommended type of therapy and its personalization for each patient as rapidly as possible.”