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FDA expands award to Wyss Institute for radiation treatment studies using Organ Chips

Project will study differences in how male and female bone marrow responds to radiation

By Lindsay Brownell

(BOSTON) — Although only one chromosome determines the genetic differences between men and women, scientific evidence suggests that this small change has a significant impact on how medical conditions and their treatments affect both sexes. The US Food and Drug Administration (FDA) has awarded the Wyss Institute at Harvard University funding to investigate how male and female bone marrow responds to radiation and drugs known to cause bone marrow damage. This award is an expansion of the FDA’s grant funding over the past five years to the Wyss Institute team for a project that uses its Organs-on-Chips (Organ Chips) technology to model how human bone marrow, lung, and intestine respond to radiation, and to develop new countermeasure therapies. The project update was announced on the FDA’s website.

“This award is a tremendous validation of the exciting results we have obtained with prior FDA funding in which we were able to faithfully mimic the organ-specific sensitivities of human organs in vitro using our Organ Chip technology. We are now in a position to ask the fundamental and clinically important question of how the bone marrow of men and women differ in their responses not only to radiation, but to drugs as well,” said Wyss Founding Director Donald Ingber, M.D., Ph.D., who is the lead investigator on the project. Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School (HMS) and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at Harvard’s John A. Paulson School of Engineering and Applied Sciences (SEAS).

Immunofluorescent image demonstrating the multiple cell types that arise within the human bone marrow chip (magenta: erythroid cells, yellow: megakaryocytes, blue: other CD45+ hematopoietic cells). Credit: Wyss Institute at Harvard University

Radiation, either a small dose in the form of cancer treatment or a large dose from a nuclear accident or attack, damages the body’s tissues and can lead to life-threatening suppression of blood cell production in the bone marrow. Studying the toxic effects of radiation and drugs such as chemotherapy agents in animal models is challenging, because humans can respond very differently to both.

In 2013, the Wyss Institute received a research award from the FDA to overcome these challenges, and to develop in vitro human models that could be used to develop new radiation countermeasure therapies. Wyss scientists have developed radiation toxicity models in their lung, gut, and bone marrow Organ Chips, and used those chips to study organ-specific responses to medical countermeasures that combat the damage. Among other results, their research has demonstrated that the Bone Marrow Chip produces human red and white blood cells (primary functions of bone marrow in vivo) for up to one month in culture, and mimics the marrow’s responses to acute radiation exposure, chemotherapy, and radiation countermeasure drugs.

Because scientific evidence indicates that sex differences may play a major role in how bone marrow responds to radiation and drugs, the new follow-on study will use these bone marrow chips to evaluate how male and female bone marrow cells respond to ionizing radiation and a chemotherapeutic drug. The insights learned from this research will help improve our understanding of how sex differences impact the body’s response to radiation countermeasure drugs and, if successful, these Organ Chip models may help scientists design more effective drugs and clinical trials in the future.

“With this additional funding, we’re hoping to answer some fundamental questions about how men’s and women’s bodies behave, as well as help develop new treatments that are specifically tailored for each sex’s unique physiological needs,” said Rachelle Prantil-Braun, Ph.D., a Senior Staff Scientist at the Wyss Institute who is helping to lead the FDA research project.

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