Animal models of skin regeneration

Cutaneous injury in the majority of vertebrate animals results in the formation of a scar in the post-injured area. Scar tissues, although beneficial for maintaining integrity of the post-wounded region often interferes with full recovery of injured tissues. The goal of wound-healing studies is to identify mechanisms to redirect reparative pathways from debilitating scar formation to regenerative pathways that lead to normal functionality. To perform such studies models of regeneration, which are rare in mammals, are required. In this review we discussed skin regenerative capabilities present in lower vertebrates and in models of skin scar-free healing in mammals, e.g. mammalian fetuses. However, we especially focused on the attributes of two unusual models of skin scar-free healing capabilities that occur in adult mammals, that is, those associated with nude, FOXN1-deficient mice and in wild-type African spiny mice.     

Stem cells and skin regeneration

Stem cells represent a great hope for regenerative medicine. In adult life, stem cell deposits are kept in organ niches; the need for tissue or organ regeneration mobilizes stem cells via the SDF-1-CXCR4 regulation axis. Constant regeneration of the skin is achieved due to stem cell differentiation within the epidermis and the hair follicle; thus, skin may serve as an excellent source of stem cells. This is of paramount importance in the treatment of chronic skin wounds and burns.     

Liposomal form of dihydroquercetin contributes to skin regeneration after thermal burns

It was found that dihydroquercetin, a flavonoid of plant origin, localized in lecitin nanoparticles with glycine amino acid, reduced inflammatory reactions in wound zones after thermal burns. The application of the liposomal complex to burn trauma stabilized the endogenous antioxidant system and minimized the area of secondary necrosis in the wound. The intensification of skin regeneration and repair of hair follicles and sebaceous glands were also observed.     

RNAi functionalized scaffold for scarless skin regeneration

Combination of a 3-D scaffold with the emerging RNA interference (RNAi) technique represents the latest paradigm of regenerative medicine. In our recent paper “RNAi functionalized collagen-chitosan/silicone membrane bilayer dermal equivalent for full-thickness skin regeneration with inhibited scarring” in the journal Biomaterials, we not only demonstrated a 3-D system for siRNA sustained delivery, but also presented a comprehensive in vivo study by targeting a vital problem in skin regeneration: scarring. It is expected that further development of this kind of RNAi functionalized scaffold can provide a better platform for directing cell fates by integrating the “down-regulating” biomolecular cues into the cellular microenvironment, leading to the complete functional regeneration of skin.     

Plasma-treated silk fibroin nanofibers for skin regeneration

Silk fibroin (SF) nanofibers were prepared by electrospinning and treated with plasma in the presence of oxygen or methane gas to modify their surface characteristics. The surface characteristics of the SF nanofibers after plasma treatment were examined using contact angle measurements and XPS analysis. The hydrophilicity of the electrospun SF nanofibers decreased slightly by the CH₄ plasma treatment. On the other hand, the hydrophilicity of the SF nanofibers increased greatly by an O₂ plasma treatment. The O₂-treated SF nanofibers showed higher cellular activities for both normal human epidermal keratinocytes (NHEK) and fibroblasts (NHEF) than the untreated ones.     

Pathways to Parkinsonism

A novel gene for Parkinson's disease (PD), DJ-1, has been identified that encodes a multifunctional product with several known protein-protein interactions and effects on gene expression. Here, I outline how it is possible to construct hypotheses that place DJ-1 in different relationships to the other known PD genes, alpha-synuclein and parkin. The identification of multiple genetic causes will provide further impetus to describe the pathway leading to PD.     

Pathways to chromothripsis

Chromothripsis is a recently recognized mode of genetic instability that generates chromosomes with strikingly large numbers of segmental re-arrangements. While the characterization of these derivative chromosomes has provided new insights into the processes by which cancer genomes can evolve, the underlying signaling events and molecular mechanisms remain unknown. In medulloblastomas, chromothripsis has been observed to occur in the context of mutational inactivation of p53 and activation of the canonical Hedgehog (Hh) pathway. Recent studies have illuminated mechanistic links between these 2 signaling pathways, including a novel PTCH1 homolog that is regulated by p53. Here, we integrate this new pathway into a hypothetical model for the catastrophic DNA breakage that appears to trigger profound chromosomal rearrangements.     

Bone marrow-derived stem cells contribute skin regeneration in skin and soft tissue expansion

Skin and soft tissue expansion stimulates the proliferation of skin epidermal basal cells and increase the dermal collagen deposition and angiogenesis. To explore the contribution of bone marrow‐derived stem cells (BMSCs) to the generation of “new” skin during the expansion, we used a chimeric mouse model in which the donor C57BL mice were engrafted with the bone marrow of enhanced green fluorescent protein (EGFP) transgenic mice. BMSCs were collected from the tibia and femur of EGFP⁺ transgenic mice, and then injected into normal C57BL mice via the tail vein (chimeric mice). Skin was obtained at different times (days 0, 7, 14, 21, 28, and 35). Skin stromal‐derived factor‐1 (SDF‐1) expression was evaluated. The number, distribution, and phenotype changes of EGFP⁺ cells in the skin were also evaluated by means of fluorescent microscopy. EGFP⁺ cells were present stably in the normal skin. The number of EGFP⁺ cells of the Group A mice changed with the tension, and reached the peak on day 21(17.1 ± 6.7%), as compared with either Group B (5.5 ± 1.0%) or Group C (5.1 ± 0.9%). The SDF‐1 expression in the expanded skin was significant increased (≈11‐fold, P < 0.01) compared to non‐expanded skin on day 21. Immunofluorescence showed EGFP⁺ cells were converted into vascular endothelial cells, epidermal cells, and spindle‐shaped dermal fibroblasts. Strain can promote the expression of SDF‐1 and facilitate the differentiation and proliferation of BMSCs in the expanded skin. J. Cell. Physiol. 226: 2834–2840, 2011. © 2011 Wiley‐Liss, Inc.     

The regeneration of axolotl limbs covered by frog skin

Forearm skin of Stage XXIV Rana pipiens, which cannot regenerate limbs, was removed and placed upon the skinned forearms of young axolotls. The axolotl limbs were amputated immediately through the level of the grafts. Frog epidermis migrated to cover the amputation surface. Dedifferentiation and early blastema formation occurred beneath the frog wound epidermis. Limb regeneration continued, but in time axolotl epidermis overgrew the frog epidermis. The experiment shows that epidermis from nonregenerating frog limbs is still capable of supporting typical epimorphic regeneration.