title: Superior angiogenesis facilitates digit regrowth in MRL/MpJ mice compared to C57BL/6 mice.
abstract: Previous studies indicated that the fast-healer strain of MRL/MpJ-Fas(lpr)/J (MRL) mice demonstrated superior regenerative capabilities for digit wound healing and/or regeneration compared with the non-healer strain of C57BL/6 (C57) mice. These reports, however, mainly focused on morphological observations and analysis of gene expression with little attention on the role of angiogenesis in the amputated digits. By taking advantage of Laser Doppler Imaging and histological analysis, we examined the potential role(s) of angiogenesis in facilitating tissue regrowth/regeneration by comparing two strains of mice (MRL versus C57). The three middle digits on the mouse's right foot (RF) were amputated at the middle level of phalanx 2 (P2) on postnatal day 2 (Day 0), while the left foot (LF) remained intact and served as a control. Laser Doppler images and digital photographs were taken of both feet before, immediately after surgery, and on Day 7, 14, 21, and 28 to evaluate blood flow and overall length of digit regrowth. All measurements from the amputated digits of the RF were divided by those of the control LF to obtain normalized ratios for statistical comparisons between groups. It was found that MRL mice demonstrated an approximately 220% increase in regrowth ratios over that of C57 mice from Day 21-28 (p < 0.01, n = 13), while blood-flow increased by about 25% on Day 21 (p < 0.01, n = 13) compared to that in C57 mice. Histological analysis of both control and amputated limbs indicated an approximately 70% increase in the number of vessels (both arterial and venous) in MRL mice over that of the C57 mice (p < 0.05, n = 3). We conclude that higher blood flow and angiogenesis may play an important role in facilitating the fast regrowth ratios of amputated digits in MRL mice compared to C57 mice.
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kwiatkowski
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Piatkowski
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Miao
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Kan
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA 24061, USA; Research Institute of Heart Failure, Shanghai East Hospital of Tongji University, Shanghai 200120, PR China.
authors.forename: Qingshu
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Research Institute of Heart Failure, Shanghai East Hospital of Tongji University, Shanghai 200120, PR China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Cytology and Histology, Suez Canal University, Ismailia 41511, Egypt.
authors.forename: Abdel-Hamid K
authors.initials: AK
authors.lastname: Osman
authors.affiliation: Research Institute of Heart Failure, Shanghai East Hospital of Tongji University, Shanghai 200120, PR China.
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ledford
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA 24061, USA. Electronic address: jiahe@vt.edu.
authors.forename: Jia-Qiang
authors.initials: JQ
authors.lastname: He
mesh_terms: D000818:Animals; D005528:Foot / Q000000981:diagnostic imaging; D017078:Laser-Doppler Flowmetry; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018919:Neovascularization, Physiologic; D012039:Regional Blood Flow; D014034:Toes / Q000098:blood supply / Q000000981:diagnostic imaging / Q000502:physiology*; D014945:Wound Healing
keywords: Angiogenesis; C57 mice; Digit regrowth; Laser doppler; MRL mice; Wound healing