Macrophages and fibroblasts during inflammation and tissue repair in models of organ regeneration

Abstract

This review provides a concise summary of the changing phenotypes of macrophages and fibroblastic cells during the local inflammatory response, the onset of tissue repair, and the resolution of inflammation which follow injury to an organ. Both cell populations respond directly to damage and present coordinated sequences of activation states which determine the reparative outcome, ranging from true regeneration of the organ to fibrosis and variable functional deficits. Recent work with mammalian models of organ regeneration, including regeneration of full‐thickness skin, hair follicles, ear punch tissues, and digit tips, is summarized and the roles of local immune cells in these systems are discussed. New investigations of the early phase of amphibian limb and tail regeneration, including the effects of pro‐inflammatory and anti‐inflammatory agents, are then briefly discussed, focusing on the transition from the normally covert inflammatory response to the initiation of the regeneration blastema by migrating fibroblasts and the expression of genes for limb patterning.

Origin and functional heterogeneity of fibroblasts

“…These balancing events may however produce overshoots, manifested by sustained and unwanted fibroblast activity and chronic inflammation in affected tissue. The fibroblast‐immune crosstalk has been the focus of other reviews and will only be discussed here with respect to novel approaches aimed to dissect the rate limiting functions of fibroblasts on innate and adaptive immune reactions.…”

Mechanisms of urodele limb regeneration

“…The immune system plays an important role in wound repair and regeneration (for reviews see Eming, Wynn, & Martin, 2017; Mescher 2017; Mescher, Neff & King, 2017). Macrophages of the innate immune system are a central mediator of wound repair in mammals.…”

“…Urodeles, which can regenerate limbs as larvae and adults, have a much less developed immune system than anurans (frogs and toads), which regenerate limbs only as early tadpoles, and mammals, which have no limb regenerative power except for digit tips. Macrophages are particularly important for the events of blastema formation during urodele limb regeneration (Godwin & Brockes, 2006; Godwin & Rosenthal, 2014; Mescher, 2017; Mescher et al, 2017; for reviews).…”

Expressing of Cytochrome-c, ADAM 17, Wnt-5a, and Hedgehog gene during the tissue regeneration of digit tip mice (Mus musculus) var Swiss Webster post amputation

“…Histological analysis indicated the continuous growth of visible bone, dermis, ragged nail, and connective tissue re-formed the new digit tip mice. According to Meschner, in this sufficiently completed phase, the specific activity of the specialized cell is progressively increased because of active to extensive regeneration and maturation naturally forming the new tissue (Mescher, 2017).…”

“…In the inflammatory phase, the specific tissue typically dominated white blood cells whose key role in phagocytosis the damaged cells. In the inflammatory phase, the specific tissue typically dominated white blood cells whose key role in phagocytosis the damaged cells (Mescher, 2017).…”