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Lee’s NSF CAREER Grant Aims to Understand How Bone and Blood Biology Are Coupled in Trabecular Bone Cavities

Jungwoo Lee

Jungwoo Lee

Assistant Professor Jungwoo Lee of the Chemical Engineering (ChE) Department is the principal investigator in a five-year, $549,710 grant from the coveted National Science Foundation (NSF) Faculty Early Career Development (CAREER) Program. Lee’s NSF research could lead to a greater understanding through which bone remodeling and blood-forming processes are functionally coupled in trabecular bone cavities via creating tissue engineered hematopoietic trabecular bone marrow models.

Lee runs the Lee Research Group, which is an interdisciplinary research team in the ChE department and the Institute for Applied Life Sciences at the University of Massachusetts Amherst.

“The mission of our laboratory is to deliver enabling and translational platform technologies that can advance basic biomedical research, solve various medical problems, and ultimately improve patient care,” says Lee. “We design and manufacture a broad range of materials to construct standardized, functional, human-tissue models and apply multi-dimensional imaging modalities to quantitatively capture complex and dynamic biological processes.”
  
As Lee sets the stage for his NSF CAREER research, “Every day, the human body’s pool of blood-forming stem cells, termed hematopoietic stem cells, develop into nearly one trillion mature blood cells, including red blood cells, white blood cells, platelets, and immune cells. These blood-cell-forming hematopoietic stem cells primarily reside and function in trabecular bone marrow, which is the tissue in the porous end of long bones such as femurs.”

Lee adds that, in essence, trabecular bone marrow can be considered as a natural bioreactor that supplies blood cells throughout life. Trabecular bone is known to undergo repeated bone remodeling throughout a lifetime.

“It has been proposed that blood and bone biology are functionally coupled in trabecular bone cavities,” says Lee, “but detailed investigation has been limited due to anatomical inaccessibility and lack of in vitro models that can faithfully recapitulate trabecular bone marrow tissue complexity.”

From a material aspect, as Lee explains, trabecular bone marrow is a composite: bone is the hardest, and marrow is the softest tissue. These two distinct mechanical tissues are integrated in trabecular bone cavities.

“We propose that development of a trabecular bone marrow tissue model requires two different biomaterial platforms that can separately mimic bone and marrow tissue mechanics in an integrated manner,” says Lee.

Lee notes that Yongkuk Park, a talented graduate student in the ChE department, has established foundational biomaterial platforms and begun to validate their biological significance.

According to Lee, ultimately, established bone marrow tissue models are expected to advance expansion of hematopoietic stem cells outside of the body without losing their intrinsic stemness, which will revolutionize future hematopoietic stem cell transplantation, also known as bone marrow transplantation.

“Hematopoietic stem cell transplantation is the most successful stem cell therapy,” says Lee, “but limited availability of hematopoietic stem cells has been a chronic limitation. Expansion of hematopoietic stem cells has long been pursued, but with limited success, because they tend to change characteristics and lose their ability to develop into any blood cell type, a process known as ‘differentiation.’”

Lee says that “The goal of this CAREER project is to develop biomaterial models that mimic the microenvironments of trabecular bone marrow for growth and maintenance of hematopoietic stem cells without allowing differentiation. Once developed, the biomaterial models will be integrated into a scalable trabecular bone marrow bioreactor to expand hematopoietic stem cells.”

Furthermore, the project will be used to recruit and educate students with diverse backgrounds to face emerging challenges at the intersection between engineering and medicine. Planned activities include an integrated lecture and lab curriculum for a tissue-engineering course, an interdisciplinary, team-based (engineering and biology) capstone project for undergraduate students, and a summer research program for high school women aligned with the existing Engineering the Cell program led by Professor Shelly Peyton (https://www.peytonlab.org/etc).

Lee explains that his long-term research goals are to deliver translational bioengineered solutions that can advance our understanding of the trabecular bone marrow in health and disease and harness the regenerative potential of the trabecular bone marrow. For example, successful trabecular bone marrow models can advance our understanding of bone remodeling during the aging process and the development of osteoporosis, bone cancers, and other diseases.

“Toward this goal,” Lee says, “the aim of this CAREER project is to elucidate the dynamic structure-function relationship that maintains hematopoietic activity in the tubercular bone marrow and to apply this knowledge to design a scalable bioreactor for expanding hematopoietic stem cells.” (March 2020)

 
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