About the book
Fibroblasts are vital structural cells of the human body with core roles in homeostasis and disease. While primarily recognized as producers of extracellular matrix and central effectors in wound healing, using them as feeder layer in cell culturing shed some understanding of their nurturing roles for other cell types. Recent years have brought remarkable advances in molecular characterization of fibroblasts, decoding their site-specificity, reactivity, heterogeneity and plasticity across the human body in health and disease. This knowledge has substantially changed our conventional views about fibroblast roles in human disease. In 2021, fibroblasts are widely recognized for their active contribution to chronicity, recurrence, progression and therapeutic resistance of many human pathologies, including cancer, chronic inflammatory and systemic autoimmune diseases.
This book provides essential insights into shared and unique characteristics of human and murine fibroblasts across the body, their crosstalk with the innate and adaptive immune systems, other tissue-resident stromal cells and cancer cells, thereby explaining fibroblast roles in shaping tissue microenvironments and structural immunity. We discuss the recent discoveries about homeostatic and pathogenic fibroblast actions in mechanotransduction, tissue remodeling, repair, inflammation, angiogenesis and lymphangiogenesis, particularly in cancer and autoimmune diseases. Metabolic reprogramming of fibroblasts is reviewed as a fundamental mechanism in pathological fibroblast switching from a quiescent to an activated cell phenotype. We delve into the embryonically-imprinted positional memories of tissue-resident fibroblasts and review their implications for the organ-specific tropism of human pathologies such as arthritis and cancer metastasis (seed and soil principle). Finally, we utilize the available fibroblast knowledge to propose novel concepts for therapeutic targeting of fibroblasts in human disease focusing on drug discovery, shared and unique fibroblast mechanisms and the capacity for therapeutic repurposing across human pathologies.