Lymphatic capillaries, the highly permeable microvessels responsible for draining and processing extracellular fluid and macromolecules out of tissue, may help regulate the microenvironments of stem cells and coordinate tissue regeneration after injury or damage, according to a study published in Science.
Tissues rely on stem cells for essential processes such as homeostasis and wound-repair. Stem cells in tissue are located in specialized microenvironments, or niches, whose specific role in spearheading tissue growth and regeneration has, until now, been unclear.
“My research focus is on the general role of lymphatics in development and disease and what I found most fascinating from our findings was that lymphatics play different roles in organ specific tissues throughout the entire body,” said Xiaolei Liu, PhD, research assistant professor of Medicine in the Division of Nephrology and Hypertension and co-author of the study.
The general role of lymphatics is to maintain tissue fluid balance, immune surveillance and lipid absorption, according to Liu. They are also the first line of defense against a number of diseases, such as lymphedema, cardiovascular disease and breast cancer, among others. However, the role lymphatics play in the regeneration of specific organs and tissue isn’t well known.
By analyzing a lymphatic defective mouse model provided by Liu in the lab of Guillermo Oliver, PhD, director of the Center for Vascular and Developmental Biology and the Thomas D. Spies Professor of Lymphatic Metabolism, a team of investigators led by Shiri Gur-Cohen, PhD, a postdoctoral fellow in the laboratory of Elaine Fuchs, PhD, at Rockefeller University, unexpectedly revealed that hair follicle stem cells are closely associated with lymphatic capillaries, specifically that lymphatic network integrity and drainage ability can orchestrate tissue regeneration.
Hair follicles in mice offered a particularly attractive model for exploring the molecular mechanisms underlying the remarkable ability of stem cells to make and repair tissues throughout the lifetime of the animal, according to the investigators.
In short, when hair follicles regenerate, lymphatic-stem cell connections become dynamic. Once the lymphatic bed has been perturbed, or when the secretome switch within stem cells that controls lymphatic behavior is disrupted, hair follicles develop and tissue regeneration takes full effect.
The scientists refer to this process as a two-way street: the remodeling of lymphatic capillaries is controlled by the stem cells, while the lymphatics control stem cell behavior.
“These important and new findings were uniquely possible due to the collaborative efforts and complementary expertise of the Fuchs and Oliver laboratories,” Liu and Gur-Cohen said, noting that next steps will include finding a way to manipulate lymphatics for hair growth to gain a better understanding of what needs to be drained form the tissue in order to allow proper tissue regeneration for life.
Oliver is also a professor of Medicine in the Division of Nephrology and Hypertension and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
This study was funded by NIH grants R01-AR050452 and R01-AR31737.