Issue link: https://viewer.e-digitaledition.com/i/394438
S C I E N T I S T S AT T H E university's Wyss Institute for Biologically Inspired Engineering recently induced living bone marrow to grow inside an artifi cial bone frame implanted under the skin of a mouse. The researchers placed the marrow in a microfl uidic device, which sustained the marrow for up to a week. The creation of bone marrow-on-a-chip follows the team's successful engineering of heart, lung and other organs-on-a-chip, and may allow researchers to test drugs on bone marrow and study blood diseases without conducting animal testing. "B one marrow is the source of all blood produced throughout the life of an organism," says Yu-suke Torisawa, PhD, Research Associate at the Wyss Institute. "Thus, we set out to develop a bone marrow-on-a-chip system with the long-term goal of enabling blood production and transport of nutrients to con- nected organs-on-a-chip. "Our method enabled us to regenerate the complex structural, physical and cellular microenvironment of whole bone marrow in vivo. We then leveraged microfl uidic strategies to deliver nutrients and other soluble signals to support the viability and function of the engineered bone marrow in vitro." Delicate Work To create the bone marrow, researchers placed demineralized bone powder, collagen gel and bone morphogenetic proteins inside a template, which they then inserted under the skin of a mouse for four to eight weeks. "We produced a cortical shell of bone and an internal trabecular bone network containing marrow with a blood cell composition nearly identical to that of natural bone marrow," Torisawa says. "The cellular content of the engineered bone marrow closely resembles the natural bone marrow microenvironment." The team placed the cylindrical bone marrow — only 1 millimeter high and 4 millimeters wide — inside a minus- cule device inscribed with channels for f luid movement. Permeable membranes surrounded the marrow's chamber, allowing the scientists to sustain the marrow with nutrients and remove waste. "The bone marrow-on-a-chip can support hematopoietic stem and progenitor cells [cells that give rise to blood cells] in normal, in vivo-like proportions, whereas conventional bone marrow culture methods do not maintain these proportions," Torisawa says. "Furthermore, this system closely mimics organ-level marrow responses to radiation toxicity normally only observed in vivo." Exciting Implications According to Torisawa, bone marrow-on-a-chip may be used to: + Assess drugs for bone marrow toxicity + Develop and test drugs to prevent bone marrow breakdown due to acute radiation syndrome + Glean insights that will improve bone marrow transplantation + Model blood diseases and develop new medications to treat them "We hope bone marrow-on-a-chip will accelerate drug discov- ery and biotechnological innovations to improve our ability to treat patients with blood-related diseases," Torisawa says. "We think this system has the ability to transform the effi cacy with which we move science from bench to bedside." ■ By Thomas Crocker RESEARCHERS AT HARVARD UNIVERSITY ARE MODELING HUMAN PHYSIOLOGICAL PROCESSES BY MICROENGINEERING ORGANS THAT FUNCTION AND WITHSTAND STUDY IN VITRO — ORGANS-ON-A-CHIP. THEIR LATEST SUCCESS, AND ONE THAT HAS SIGNIFICANT TREATMENT IMPLICATIONS: BONE MARROW. Microengineering the Body, Chip by Chip ++++++++++++++++++++ + +++ + +++ ++++++++++++++++++++ TECHNOLOGY 1 6 | Long Island MD NEWS ■ M D N E W S . CO M