This November, Professor Bill Thilly ’67, ScD ‘71 and research scientist Dr. Elena Gostjeva celebrated an anniversary with the help of friends and research collaborators. It wasn’t a wedding anniversary—though the Thilly and Gostjeva have been married and working together for nearly two decades—but the fourteenth anniversary of Gostjeva’s discovery of metakaryotic stem cells. Thilly and Gostjeva believe that these bizarre cells serve as the stem cells of organ growth and development and also wound healing. But when they go awry, metakaryotes drive the formation of tumors, making the cells sources of cancer insights as well as targets for potential therapies.
Gostjeva discovered the metakaryotic cells using a specialized imaging system developed for Soviet satellite surveillance coupled with a tissue preparation technique that she brought from her previous work in botanical cytogenetics. Tumors and developing tissue revealed strange-looking cells with open-mouthed bell shaped nuclei. Gostjeva named the cells metakaryotes because they didn’t fit the confines of eukaryotic cells—cells with a nucleus that are building blocks for many forms of life including humans—or prokaryotic cells—cells without a nucleus that are the foundation for bacteria and algae. “Biology in high schools and universities taught us that all human cells including embryonic stem cells were eukaryotic, but Gostjeva’s cells were markedly different,” Thilly recalls.
In the years since the discovery, Thilly and Gostjeva have worked with several MIT researchers and students to learn more about these cells. Because of their role in creating tumors, Thilly says that metakaryotic stem cells are clear targets for cancer therapy, noting that the cells may the also be targets in treating other diseases. “They also appear to be the stem cells of atheroscleroses, restenoses, sclerodermas, and other lesions,” Thilly explains.
Though the metakaryotic cells provide a key target for cancer treatment, researchers found that the cells didn’t respond to cancer treatments the same way eukaryotic cells did—they weren’t killed by x-ray or any of many chemotherapeutic drugs at levels in common use. “Clearly one wanted drugs that did kill the cancer stem cells,” Thilly says. So they turned their focus toward drugs reported to interfere with fetal development and or wound healing—key activities of the metakaryotic cells. “Bingo!” Thilly says. “Common drugs such as NSAIDs and some antibiotics kill metakaryotic cancer stem cells at levels that do not kill eukaryotic cancer cells. Importantly they appear to act at concentrations that could be well tolerated by patients.” A common antibiotic is currently in a clinical trial directed by Dr. Susan Tsai ‘97 at the Medical College of Wisconsin. Thilly says the hope is that a first drug will kill most of the metakaryotic cancer stem cells and subsequent treatment with other drugs could destroy the tumor and its metastases.
Tsai isn’t the only MIT alumna to work with Thilly and Gostjeva—alumna Beth Furth ’78, SM ’79 was with the two at their recent research celebration. Thilly and Gostjeva look forward to celebrating their fifteen year anniversary of the discovery—and the completion of the first single drug clinical trial—in 2018.
Above image: Typical form of metakaryotic nuclear amitotic “cup-from-cup" mode seen both in fetal and tumor development.