Organoid Tech Brings Hadassah Medicine to a New Level
In a chamber deep within the rocky Judean Hills, suspended in liquid nitrogen at a mind-numbingly cold -320°, are frontline technological tools that are transforming health care. They are organoids: tiny clumps of tissue developed from stem cells that function much as tissues do in the human body.
The organoids, which range in size from several millimeters to less than the width of a hair, have been grown in the labs of the Hadassah Medical Organization on the Ein Kerem campus, some from no more than a single cell. They are being used both to research diseases and determine the best treatment for individual patients.
Welcome to HMO’s Organoid Center. Opened in October 2020 within the Wohl Institute for Translational Medicine, it is the first biobank of its kind in Israel and one of only a handful worldwide.
“Organoid technology is enabling Hadassah to take targeted, personalized medicine to a new level, to advance innovative drug development and to create a human-tissue research platform for the global scientific community,” said Dr. Eyal Mishani, director-general of Hadassah’s Research Fund and director of the Research and Development and Innovation Division, who led the establishment of the Organoid Center.
To date, 145 patients have contributed cells from which organoids can be derived, with that number increasing each week. Among these contributors is a 48-year-old woman who battled an aggressive breast cancer for eight years. Her oncologist, Dr. Tamar Peretz, had contacted the center, and with the woman’s agreement, cells from her tumor were sent to the biobank.
“Within a week we derived sufficient organoids from this patient’s tumor cells to screen several possible medications,” said Myriam Grune-wald, Ph.D., who heads the center and is its scientific director. “We found that an FDA-approved drug, not generally used in cancer patients, offered her the best outcome.”
Another biobank donor is a woman whose difficult-to-treat asthma turned out to be cystic fibrosis (CF), a diagnosis she recently received at age 36. “We used her organoids for drug screening and could confidently tell her clinician: ‘Of the CF medications available, this is the recommended regimen,’ ” said the center’s clinical director, pediatric gastroenterologist Dr. Liron Birimberg-Schwartz.
The organoids created from these cells are not only helping patients—ending the trial and error of traditional clinical care—they are also being used as the best model yet for investigating human disease.
Take cancer, for example, a major research focus at HMO. The traditional research models are two-dimensional cell cultures and lab animals, “but neither maintains the heterogeneity or complex interactions of human cancer cells,” explained Grunewald. “Not only is this maintained in patient-derived tumor organoids, but they can also be expanded, stored and used to develop new drugs for cancer and other research.”
Also being investigated at the center is the hereditary eye disease retinitis pigmentosa, which blinds sufferers by destroying the retina’s vital light-absorbing photoreceptors. The center is in the process of creating organoids from two siblings—one, age 7, who has the mutation for retinitis pigmentosa, and his 11-year-old brother, who does not. “They’ll help us understand the disease mechanism and enable us to test drugs that prevent or at least significantly delay death of the photoreceptor cells,” said Grunewald. “Long term, we’re looking for a way to grow and transplant healthy retinas.”
Organoid technology is only 14 years old. Its basis is the cells with regenerative potential known as stem cells. Dutch geneticist Dr. Hans Clevers and his team at Utrecht’s Hubrecht Institute in the Netherlands identified adult stem cells in tissue biopsied from the small intestine of a mouse. They coaxed the cells to follow their genetic programming in their lab and watched them assemble themselves into three-dimensional tissue structures. These were the first organoids.
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For HMO, an organoid biobank was an obvious step. “We’re a stem-cell research pioneer, we’ve always emphasized translational medicine, and we have a proud history of innovation,” said Dr. Mishani, the driver behind much of that innovation. “I presented it at a Hadassah conference in Boston in 2022 and a $250,000 contribution was immediately forthcoming. Ultimately, Hadassah, The Women’s Zionist Organization of America, funded 80 percent of Hadassah’s Organoid Center.”
To bring organoid technology to HMO, Dr. Mishani turned to Grune-wald and Dr. Birimberg-Schwartz. The former grew up in southern France, moved to Israel over 30 years ago and received a doctorate from the Hebrew University of Jerusalem. She was working on the physiology of the vascular system when Dr. Mishani approached her. “I immediately accepted the challenge,” Grunewald said.
Dr. Birimberg-Schwartz, who was born in Israel and trained at Hadassah’s medical school, was in Toronto on a gastroenterology fellowship at the Hospital for Sick Children, which was already exploring organoid technology. “As part of our research, we screened the organoids of a CF patient for whom no effective medication was available—and found a drug combination that worked for her,” she recalled of her work in Toronto. “This changed my path as a clinician.”
Grunewald and Dr. Birimberg-Schwartz lead a staff of 10 at the center, among them research scientists and biotechnology doctoral candidates.
“Each week, we review the medical organization’s scheduled biopsies and surgeries, and select about four patients to expand the biobank,” explained Grunewald. “The oldest patient to donate tissue, to date, is an 85-year-old woman who underwent resection of her endometrium. The youngest has a rare genetic disease that impacted her intestines and was 7 when we received her intestine biopsies.”
Patients or guardians give written informed consent for the tissue, healthy and diseased, to be included in the bank. Each sample is documented with details of the patient, physicians, treatments, medications and follow-up.
Once the center receives the tissue sample, it cultures the sample in a specific way. The cells reproduce, interconnect and arrange themselves in the culture dish as they would in the human body. The three-dimensional organoids they form are smaller versions of the tissues from which they come, virtually identical both molecularly and functionally. They are then deep-frozen in HMO’s underground liquid nitrogen bank until needed.
Progress has been made since the technology was developed in the Netherlands in 2009. “At Hadassah today, we grow organoids from almost any tissue in the human body,” said Grunewald. “The patient with breast cancer was too sick to biopsy, so we took fluid draining from her lungs, found tumor cells there and created organoids—the first in Israel to do so from this buildup of excess fluid in the lungs.”
The organoids in Hadassah’s biobank can help develop new medical technology worldwide. “While organoids are used for research in several labs, those in Hadassah’s biobank are accessible to the entire scientific community—researchers, clinicians, pharmaceutical companies,” said Dr. Birimberg-Schwartz. “Within Hadassah, the technology is applied to personalized medicine, examining new drugs and repurposing existing medications in a two-way communication between medical center clinicians and scientists.”
As the technology races forward, “organoids will provide solutions for testing costly medicines and for currently nonprofitable research into rare mutations and orphan diseases,” according to Dr. Mishani. “And,” he continued, “the contribution of organoids is still only partly realized. Most exciting of all is that they’re emerging as a source of transplantable tissues. Down the road, they’ll likely be grown and implanted into patients to heal non-functioning tissues and organs.”
Wendy Elliman is a British-born science writer who has lived in Israel for more than four decades.