TITLE:
Mast Cells in Connective Tissue Regulation and Altered Regulation in Hypermobility Ehlers-Danlos Syndrome (hEDS): Why the Association of Mast Cell Activation Syndrome and hEDS?
AUTHORS:
David A. Hart
KEYWORDS:
Mast Cell Activation Syndrome, Joint Hypermobility, Connective Tissue Fibrosis, Wound Healing, Mast Cells and Healing Responses, Hypermobility Ehlers-Danlos Syndrome
JOURNAL NAME:
Journal of Biomedical Science and Engineering,
Vol.19 No.4,
April
30,
2026
ABSTRACT: Mast cells (MC) arose early during the evolution of the immune system. While these cells are very involved in host defense against a variety of organisms, they are also found associated with many connective tissues of the musculoskeletal system. As MC contain granules with many potent biologically active mediators and can also synthesize others, their presence in connective tissues could pose a risk for compromise of connective tissue integrity. Despite such risk, the presence of MC in these tissues may imply that they also serve functions related to tissue homeostasis, repair and adaptation, and are capable of functioning in a variety of biomechanically active environments. Their dysregulation, such as in Mast Cell Activation Syndromes (MCAS) could contribute to conditions associated with loss of connective tissue integrity. Interestingly, MCAS has also been reported to be associated with subsets of patients with hypermobility Ehlers-Danlos syndromes (hEDS). This perspective article discusses the potential roles of MC in normal connective tissue states and then discusses aspects of the relationship between MC and hEDS. It is concluded that there is a need to better understand the role of MC in this context, and how the study of the involvement of MCAS and EDS presents a model to examine these relationships in detail.