title: Wound healing and blastema formation in regenerating digit tips of adult mice.
abstract: Amputation of the distal region of the terminal phalanx of mice causes an initial wound healing response followed by blastema formation and the regeneration of the digit tip. Thus far, most regeneration studies have focused in embryonic or neonatal models and few studies have examined adult digit regeneration. Here we report on studies that include morphological, immunohistological, and volumetric analyses of adult digit regeneration stages. The regenerated digit is grossly similar to the original, but is not a perfect replacement. Re-differentiation of the digit tip occurs by intramembranous ossification forming a trabecular bone network that replaces the amputated cortical bone. The digit blastema is comprised of proliferating cells that express vimentin, a general mesenchymal marker, and by comparison to mature tissues, contains fewer endothelial cells indicative of reduced vascularity. The majority of blastemal cells expressing the stem cell marker SCA-1, also co-express the endothelial marker CD31, suggesting the presence of endothelial progenitor cells. Epidermal closure during wound healing is very slow and is characterized by a failure of the wound epidermis to close across amputated bone. Instead, the wound healing phase is associated with an osteoclast response that degrades the stump bone allowing the wound epidermis to undercut the distal bone resulting in a novel re-amputation response. Thus, the regeneration process initiates from a level that is proximal to the original plane of amputation.
authors.affiliation: Division of Developmental Biology, Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
authors.forename: Warnakulasuriya Akash
authors.initials: WA
authors.lastname: Fernando
authors.forename: Eric
authors.initials: E
authors.lastname: Leininger
authors.forename: Jennifer
authors.initials: J
authors.lastname: Simkin
authors.forename: Ni
authors.initials: N
authors.lastname: Li
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Malcom
authors.forename: Shyam
authors.initials: S
authors.lastname: Sathyamoorthi
authors.forename: Manjong
authors.initials: M
authors.lastname: Han
authors.forename: Ken
authors.initials: K
authors.lastname: Muneoka
mesh_terms: D000671:Amputation, Surgical; D000818:Animals; D000950:Antigens, Ly / Q000032:analysis; D002454:Cell Differentiation; D005121:Extremities / Q000502:physiology*; D005260:Female; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D010010:Osteoclasts / Q000502:physiology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D012038:Regeneration; D014057:Tomography, X-Ray Computed; D014945:Wound Healing
chemical_list: D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1