Proximal digit tip amputation initiates simultaneous blastema and transient fibrosis formation and results in partial regeneration.
Journal
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
ISSN: 1524-475X
Titre abrégé: Wound Repair Regen
Pays: United States
ID NLM: 9310939
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
27
04
2020
revised:
09
07
2020
accepted:
23
07
2020
pubmed:
21
8
2020
medline:
3
11
2021
entrez:
21
8
2020
Statut:
ppublish
Résumé
Complete extremity regeneration in mammals is restricted to distal amputations of the digit tip, the terminal phalanx (P3). In mice, P3 regeneration is mediated via the formation of a blastema, a transient population of progenitor cells that form from the blending of periosteal and endosteal/marrow compartmentalized cells that undergo differentiation to restore the amputated structures. Compartmentalized blastema cells are formed independently, and periosteal compartment-derived cells are required for restoration of amputated skeletal length. P3 regenerative capacity is progressively attenuated at increasingly more proximal amputation levels, eventually resulting in regenerative failure. The continuum of regenerative capacity within the P3 wound milieu is a unique model to investigate mammalian blastema formation in response to distal amputation, as well as the healing response associated with regenerative failure at proximal amputation levels. We report that P3 proximal amputation healing, previously reported to result in regenerative failure, is not an example of complete regenerative failure, but instead is characterized by a limited bone regeneration response restricted to the endosteal/marrow compartment. The regeneration response is mediated by blastema formation within the endosteal/marrow compartment, and blastemal osteogenesis progresses through intramembranous ossification in a polarized proximal to distal sequence. Unlike bone regeneration following distal P3 amputation, osteogenesis within the periosteal compartment is not observed in response to proximal P3 amputation. We provide evidence that proximal P3 amputation initiates the formation of fibrotic tissue that isolates the endosteal/marrow compartment from the periosteal compartment and wound epidermis. While the fibrotic response is transient and later resolved, these studies demonstrate that blastema formation and fibrosis can occur in close proximity, with the regenerative response dominating the final outcome. Moreover, the results suggest that the attenuated proximal P3 regeneration response is associated with the absence of periosteal-compartment participation in blastema formation and bone regeneration.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
196-205Informations de copyright
© 2020 The Wound Healing Society.
Références
Borgens RB. Mice regrow the tips of their foretoes. Science. 1982;217(4561):747-750.
Han M et al. Development and regeneration of the neonatal digit tip in mice. Dev Biol. 2008;315(1):125-135.
McKim LH. Regeneration of the distal phalanx. Can Med Assoc J. 1932;26(5):549-550.
Illingworth CM. Trapped fingers and amputated finger tips in children. J Pediatr Surg. 1974;9(6):853-858.
Douglas BS. Conservative management of guillotine amputation of the finger in children. Aust Paediatr J. 1972;8(2):86-89.
Lehoczky JA, Robert B, Tabin CJ. Mouse digit tip regeneration is mediated by fate-restricted progenitor cells. Proc Natl Acad Sci U S A. 2011;108(51):20609-20614.
Fernando WA, Leininger E, Simkin J, et al. Wound healing and blastema formation in regenerating digit tips of adult mice. Dev Biol. 2011;350(2):301-310.
Rinkevich Y, Lindau P, Ueno H, Longaker MT, Weissman IL. Germ-layer and lineage-restricted stem/progenitors regenerate the mouse digit tip. Nature. 2011;476(7361):409-413.
Takeo M, Chou WC, Sun Q, et al. Wnt activation in nail epithelium couples nail growth to digit regeneration. Nature. 2013;499(7457):228-232.
Carr MJ, Toma JS, Johnston APW, et al. Mesenchymal precursor cells in adult nerves contribute to mammalian tissue repair and regeneration. Cell Stem Cell. 2019;24(2):240-256.e9.
Storer MA, Mahmud N, Karamboulas K, et al. Acquisition of a unique mesenchymal precursor-like blastema state underlies successful adult mammalian digit tip regeneration. Dev Cell. 2020;52(4):509-524.e9.
Neufeld DA. Bone healing after amputation of mouse digits and newt limbs: implications for induced regeneration in mammals. Anat Rec. 1985;211(2):156-165.
Neufeld DA. Epidermis, basement membrane, and connective-tissue healing after amputation of mouse digits: implications for mammalian appendage regeneration. Anat Rec. 1989;223(4):425-432.
Said S, Parke W, Neufeld DA. Vascular supplies differ in regenerating and nonregenerating amputated rodent digits. Anat Rec A Discov Mol Cell Evol Biol. 2004;278(1):443-449.
Agrawal V, Kelly J, Tottey S, et al. An isolated cryptic peptide influences osteogenesis and bone remodeling in an adult mammalian model of digit amputation. Tissue Eng Part A. 2011;17(23-24):3033-3044.
Agrawal V, Siu BF, Chao H, et al. Partial characterization of the Sox2+ cell population in an adult murine model of digit amputation. Tissue Eng Part A. 2012;18(13-14):1454-1463.
Agrawal V, Tottey S, Johnson SA, Freund JM, Siu BF, Badylak SF. Recruitment of progenitor cells by an extracellular matrix cryptic peptide in a mouse model of digit amputation. Tissue Eng Part A. 2011;17(19-20):2435-2443.
Dawson LA, Simkin J, Sauque M, Pela M, Palkowski T, Muneoka K. Analogous cellular contribution and healing mechanisms following digit amputation and phalangeal fracture in mice. Regeneration. 2016;3(1):39-51.
Yu L, Han M, Yan M, Lee J, Muneoka K. BMP2 induces segment-specific skeletal regeneration from digit and limb amputations by establishing a new endochondral ossification center. Dev Biol. 2012;372(2):263-273.
Yu L, Dawson LA, Yan M, et al. BMP9 stimulates joint regeneration at digit amputation wounds in mice. Nat Commun. 2019;10(1):424.
Dawson LA, Yu L, Yan M, et al. The periosteal requirement and temporal dynamics of BMP2-induced middle phalanx regeneration in the adult mouse. Regeneration. 2017;4(3):140-150.
Neufeld DA, Zhao W. Phalangeal regrowth in rodents: postamputational bone regrowth depends upon the level of amputation. Prog Clin Biol Res. 1993;383a:243-252.
Chamberlain CS, Jeffery JJ, Leiferman EM, et al. Level-specific amputations and resulting regenerative outcomes in the mouse distal phalanx. Wound Repair Regen. 2017;25(3):443-453.
Han M, Yang X, Farrington JE, Muneoka K. Digit regeneration is regulated by Msx1 and BMP4 in fetal mice. Development. 2003;130(21):5123-5132.
Yu L, Han M, Yan M, Lee EC, Lee J, Muneoka K. BMP signaling induces digit regeneration in neonatal mice. Development. 2010;137(4):551-559.
Taghiyar L, Hosseini S, Hesaraki M, Azam Sayahpour F, Aghdami N, Baghaban Eslaminejad M. Isolation, characterization and osteogenic potential of mouse digit tip blastema cells in comparison with bone marrow-derived mesenchymal stem cells in vitro. Cell J. 2018;19(4):585-598.
Johnston AP et al. Dedifferentiated Schwann cell precursors secreting paracrine factors are required for regeneration of the mammalian digit tip. Cell Stem Cell. 2016;19(4):433-448.
Dolan CP, Dawson LA, Muneoka K. Digit tip regeneration: merging regeneration biology with regenerative medicine. Stem Cells Transl Med. 2018;7(3):262-270.
Dawson LA, Schanes PP, Kim P, et al. Blastema formation and periosteal ossification in the regenerating adult mouse digit. Wound Repair Regen. 2018;26(3):263-273.
Dwek JR. The periosteum: what is it, where is it, and what mimics it in its absence? Skeletal Radiol. 2010;39(4):319-323.
Dawson LA, Brunauer R, Zimmel KN, et al. Adult mouse digit amputation and regeneration: a simple model to investigate mammalian Blastema formation and intramembranous ossification. J Vis Exp. 2019;149:1-7.
Doube M, Kłosowski MM, Arganda-Carreras I, et al. BoneJ: free and extensible bone image analysis in ImageJ. Bone. 2010;47(6):1076-1079.
Simkin J, Sammarco MC, Dawson LA, et al. Epidermal closure regulates histolysis during mammalian (Mus) digit regeneration. Regeneration. 2015;2(3):106-119.
Bochaton-Piallat ML, Gabbiani G, Hinz B. The myofibroblast in wound healing and fibrosis: answered and unanswered questions. F1000Res. 2016;5.
Pakshir P, Hinz B. The big five in fibrosis: macrophages, myofibroblasts, matrix, mechanics, and miscommunication. Matrix Biol. 2018;68-69:81-93.
Yu L, Yan M, Simkin J, et al. Angiogenesis is inhibitory for mammalian digit regeneration. Regeneration. 2014;1(3):33-46.
Marrero L, Simkin J, Sammarco M, Muneoka K. Fibroblast reticular cells engineer a blastema extracellular network during digit tip regeneration in mice. Regeneration. 2017;4(2):69-84.
Carlson BM. Principles of Regenerative Biology. Burlington, MA: Elsevier; 2007.
Seifert AW, Muneoka K. The blastema and epimorphic regeneration in mammals. Dev Biol. 2018;433(2):190-199.
Sammarco MC, Simkin J, Fassler D, et al. Endogenous bone regeneration is dependent upon a dynamic oxygen event. J Bone Miner Res. 2014;29(11):2336-2345.
Lee J, Marrero L, Yu L, Dawson LA, Muneoka K, Han M. SDF-1alpha/CXCR4 signaling mediates digit tip regeneration promoted by BMP-2. Dev Biol. 2013;382(1):98-109.
Schotte EO, Smith CB. Wound healing processes in amputated mouse digits. Biol Bull. 1959;117:546-561.
Masaki H, Ide H. Regeneration potency of mouse limbs. Dev Growth Differ. 2007;49(2):89-98.
Ide H. Bone pattern formation in mouse limbs after amputation at the forearm level. Dev Dyn. 2012;241(3):435-441.
Vidal P, Dickson MG. Regeneration of the distal phalanx. A case report. J Hand Surg Br. 1993;18(2):230-233.
Dent JN. Limb regeneration in larvae and metamorphosing individuals of the south African clawed toad. J Morphol. 1962;110:61-77.
Endo T, Tamura K, Ide H. Analysis of gene expressions during Xenopus forelimb regeneration. Dev Biol. 2000;220(2):296-306.
Simkin J, Sammarco MC, Marrero L, et al. Macrophages are required to coordinate mouse digit tip regeneration. Development. 2017;144(21):3907-3916.
Sammarco MC, Simkin J, Cammack AJ, et al. Hyperbaric oxygen promotes proximal bone regeneration and organized collagen composition during digit regeneration. PLoS One. 2015;10(10):e0140156.
Tonnesen MG, Feng X, Clark RA. Angiogenesis in wound healing. J Investig Dermatol Symp Proc. 2000;5(1):40-46.
Gabbiani G, Ryan GB, Majne G. Presence of modified fibroblasts in granulation tissue and their possible role in wound contraction. Experientia. 1971;27(5):549-550.
Klingberg F, Hinz B, White ES. The myofibroblast matrix: implications for tissue repair and fibrosis. J Pathol. 2013;229(2):298-309.
Dreymueller D, Denecke B, Ludwig A, Jahnen-Dechent W. Embryonic stem cell-derived M2-like macrophages delay cutaneous wound healing. Wound Repair Regen. 2013;21(1):44-54.
Seifert AW, Monaghan JR, Voss SR, Maden M. Skin regeneration in adult axolotls: a blueprint for scar-free healing in vertebrates. PLoS One. 2012;7(4):e32875.
Seifert AW, Kiama SG, Seifert MG, Goheen JR, Palmer TM, Maden M. Skin shedding and tissue regeneration in African spiny mice (Acomys). Nature. 2012;489(7417):561-565.