Skin wounds in the MRL/MPJ mouse heal with scar.
ABSTRACT Adult MRL/MpJ mice regenerate cartilage during repair of through-and-through ear punch wounds. However, the ability of this mouse strain to heal isolated cutaneous wounds by regeneration or with scar is unknown. The purpose of this study was to characterize the rate of reepithelialization and collagen architecture in dermal wounds from MRL/MpJ mice compared with C57bl/6 and Balb/c strains. Full-thickness incisional (5 mm) and excisional (2 mm diameter) skin wounds were made on the dorsum of 7-week-old MRL/MpJ, C57bl/6, and Balb/c mice. Ear punch wounds were made simultaneously on each animal. Reepithelialization was complete by 48 hours for incisional skin wounds in each strain. All excisional wounds showed incomplete reepithelialization at 24, 48, and 72 hours. At 14 days, all skin wounds had grossly healed. In contrast to the ear wounds made in C57bl/6 and Balb/c mice, MRL/MpJ ear wounds were completely healed by day 28. Dorsal skin wound sections at 14 and 28 days revealed dense collagen deposition and similar degrees of fibrosis between the three strains of mice. In conclusion, in contrast to wound healing in the ear, MRL/MpJ mouse dorsal cutaneous wounds heal similarly to C57bl/6 and Balb/c mice with dermal collagen deposition and scar formation.
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ABSTRACT: Mammals rarely regenerate their lost or injured tissues into adulthood. MRL/MpJ mouse strain initially identified to heal full-thickness ear wounds now represents a classical example of mammalian wound regeneration since it can heal a spectrum of injuries such as skin and cardiac wounds, nerve injuries and knee articular cartilage lesions. In addition to MRL/MpJ, a few other mouse strains such as LG/J (a parent of MRL/MpJ) and LGXSM-6 (arising from an intercross between LG/J and SM/J mouse strains) have now been recognized to possess regenerative/healing abilities for articular cartilage and ear wound injuries that are similar, if not superior, to MRL/MpJ mice. While some mechanisms underlying regenerative potential have been begun to emerge, a complete set of biological processes and pathways still needs to be elucidated. Using a panel of healer and non-healer mouse strains, our recent work has provided some insights into the genes that could potentially be associated with healing potential. Future mechanistic studies can help seek the Holy Grail of regenerative medicine. This review highlights the regenerative capacity of selected mouse strains for articular cartilage, in particular, and lessons from other body tissues, in general.Matrix Biology 10/2014; 39. DOI:10.1016/j.matbio.2014.08.011 · 3.65 Impact Factor
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ABSTRACT: All species have evolved mechanisms of repair to restore tissue function following injury. Skin scarring is an inevitable and permanent end point for many post-natal organisms except for non-amniote vertebrates such as amphibians, which are capable of tissue regeneration. Furthermore, mammalian fetuses through midgestation are capable of rapid wound repair in the absence of scar formation. Notably, excessive cutaneous scar formation, such as hypertrophic and keloid scars, is a species limited clinical entity as it occurs only in humans, although wounds on the distal limbs of horses are also prone to heal with fibroproliferative pathology known as equine exuberant granulation tissue. Currently, there are no reliable treatment options to eradicate or prevent scarring in humans and vertebrates. The limited number of vertebrate models for either hypertrophic and keloid scarring has been an impediment to mechanistic studies of these diseases and the development of therapies. In this viewpoint essay, we highlight the current concepts of regenerative, scar-free and scar-forming healing compared across a number of species and speculate on areas for future research. Furthermore, in depth investigative research into the mechanisms of scarless repair may allow for the development of improved animal models and novel targets for scar prevention. As the ability to heal in both a scarless manner as well as propensity for healing with excessive scar formation are highly species dependent, understanding similarities and differences in healing across species as it relates to the regenerative process may hold the key to improve scarring and guide translational wound healing studies.This article is protected by copyright. All rights reserved.Experimental Dermatology 05/2014; 23(9). DOI:10.1111/exd.12457 · 4.12 Impact Factor
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ABSTRACT: In developing a chitosan/dextran-based (CD) hydrogel as an adhesion prevention postsurgical aid, the in vivo biodegradation rate, biodistribution, and inflammatory response are important parameters to the biomedical device design. Herein, for the first time, a CD hydrogel was prepared by mixing aqueous solutions of a near infrared (NIR) labeled succinylated chitosan (SC) and tritiated [3H] oxidized dextran (DA). The biodegradation and biodistribution of the NIR/ [3H]-CD hydrogel was tracked noninvasively using NIR fluorescence imaging, and by liquid scintillation counting (LSC) of organs/tissues after subcutaneous injection in BALB/c mice. The inflammatory response was assessed by measuring serum cytokine levels using a Bio-plex assay and by histological examination of injection site tissue. Fluorescence imaging showed the hydrogel to degrade in under a week. LSC revealed the hydrogel to reside mainly at the injection site, and excreted primarily via the urine within the first 48 h. The CD hydrogel showed a mild inflammatory response as cytokine levels were comparable to saline injected controls. Histological examination of injection site tissue confirmed the cytokine results. In summary, the CD hydrogel's in vivo biodegradation rate, biodistribution, and inflammatory response was determined. Our results indicate that the CD hydrogel has an appropriate biocompatibility after s.c. administration. This article is protected by copyright. All rights reserved.Journal of Biomedical Materials Research Part A 12/2014; DOI:10.1002/jbm.a.35395 · 2.83 Impact Factor