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The International Journal of... 2004This chapter is mostly a review of the pioneering work of the Philippe Sengel school in Grenoble carried out in the late sixties and the seventies. The questions raised... (Review)
Review
This chapter is mostly a review of the pioneering work of the Philippe Sengel school in Grenoble carried out in the late sixties and the seventies. The questions raised concerning the morphogenesis of feather tracts were approached by means of microsurgery on chick embryos. P. Sengel and his wife M. Kieny had the feeling that proteins synthesized by the neural tube were required for the formation of feather fields. It was my pleasure to carry on the story from the beginning. Although some clarifications concerning this morphogenesis have been contributed by my group and by a few other laboratories interested in this subject, the most important contributions to recent research have been the elucidation of the nature of the required messages, which will be explored further in other papers in this Issue.
Topics: Amnion; Animals; Cell Differentiation; Chick Embryo; Dermis; Epidermal Cells; Epidermis; Feathers; Humans; Mesoderm; Microscopy, Electron, Scanning; Models, Biological; Morphogenesis; Skin
PubMed: 15272373
DOI: 10.1387/ijdb.15272373 -
The Tokai Journal of Experimental and... Dec 2022Physicians occasionally come across with patients with locally advanced breast cancer (LABC) bringing about distress, due to tumor growth, invasion to the skin, bleeding...
Physicians occasionally come across with patients with locally advanced breast cancer (LABC) bringing about distress, due to tumor growth, invasion to the skin, bleeding or an ill smell. Physicians often experience much difficulty in selecting and administering therapeutic option. The clinical courses of patient who had been treated with total resection of LABC and an attachment of artificial dermis (TERUDERMIS) were mentioned. Elimination of the symptoms derived from the tumors could be successfully accomplished for all of the patients. Except for one patients who initially had bone metastasis and died 13 months after operation, the other patients have been alive under preferable condition without any signs for tumor recurrence. The surgical resection and an attachment of artificial dermis is quite reliable and helpful for both patients and physicians in palliating symptoms and reducing care for infections and hemorrhage due to LABC.
Topics: Humans; Female; Breast Neoplasms; Neoplasm Recurrence, Local; Dermis
PubMed: 36420547
DOI: No ID Found -
Skin Pharmacology and Physiology 2020The dermal papilla comprises mesenchymal cells in hair follicles, which play the main role in regulating hair growth. Maintaining the potential hair inductivity of... (Review)
Review
The dermal papilla comprises mesenchymal cells in hair follicles, which play the main role in regulating hair growth. Maintaining the potential hair inductivity of dermal papilla cells (DPCs) and dermal sheath cells during cell culture is the main factor in in vitro morphogenesis and regeneration of hair follicles. Using common methods for the cultivation of human dermal papilla reduces the maintenance requirements of the inductive capacity of the dermal papilla and the expression of specific dermal papilla biomarkers. Optimizing culture conditions is therefore crucial for DPCs. Moreover, exosomes appear to play a key role in regulating the hair follicle growth through a paracrine mechanism and provide a functional method for treating hair loss. The present review investigated the biology of DPCs, the molecular and cell signaling mechanisms contributing to hair follicle growth in humans, the properties of the dermal papilla, and the effective techniques in maintaining hair inductivity in DPC cultures in humans as well as hair follicle bioengineering.
Topics: Cell Culture Techniques; Dermis; Hair; Hair Follicle; Humans; Intercellular Signaling Peptides and Proteins; Regeneration
PubMed: 33053562
DOI: 10.1159/000510152 -
Anatomical Record. Part B, New Anatomist Nov 2005We review what is known about amphibian limb regeneration from the prospective of developing strategies for the induction of regeneration in adult mammals. Prominent in... (Review)
Review
We review what is known about amphibian limb regeneration from the prospective of developing strategies for the induction of regeneration in adult mammals. Prominent in urodele amphibian limb regeneration is the formation of a blastema of undifferentiated cells that goes on to reform the limb. The blastema shares many properties with the developing limb bud; thus, the outgrowth phase of regeneration can be thought of as cells going through development again, i.e., redevelopment. Getting to a redevelopment phase in mammals would be a major breakthrough given our extensive understanding of limb development. The formation of the blastema itself represents a transition phase in which limb cells respond to injury by dedifferentiating to become embryonic limb progenitor cells that can undergo redevelopment. During this phase, rapid wound closure is followed by the dedifferentiation of limb cells to form the blastema. Thus, the regeneration process can be divided into a wound-healing/dedifferentiation phase and a redevelopment phase, and we propose that the interface between the wound-healing response and gaining access to developmentally regulated programs (dedifferentiation) lies at the heart of the regeneration problem in mammals. In urodele amphibians, dedifferentiation can occur in all of the tissues of the limb; however, numerous studies lead us to focus on the epidermis, the dermis, and muscle as key regulators of regeneration. Among higher vertebrates, the digit tip in mammals, including humans, is regeneration-competent and offers a unique mammalian model for regeneration. Recent genetic studies in mice identify the Msx1 gene as playing a critical role in the injury response leading to digit tip regeneration. The results from regeneration studies ranging from amphibians to mammals can be integrated to develop a roadmap for mammalian regeneration that has as its focus understanding the phenomenon of dedifferentiation.
Topics: Animals; Cartilage; Dermis; Extremities; Humans; Muscles; Regeneration; Vertebrates
PubMed: 16308860
DOI: 10.1002/ar.b.20082 -
Scientific Reports Jun 2021Microphysiological organ-on-chip models offer the potential to improve the prediction of drug safety and efficacy through recapitulation of human physiological...
Microphysiological organ-on-chip models offer the potential to improve the prediction of drug safety and efficacy through recapitulation of human physiological responses. The importance of including multiple cell types within tissue models has been well documented. However, the study of cell interactions in vitro can be limited by complexity of the tissue model and throughput of current culture systems. Here, we describe the development of a co-culture microvascular model and relevant assays in a high-throughput thermoplastic organ-on-chip platform, PREDICT96. The system consists of 96 arrayed bilayer microfluidic devices containing retinal microvascular endothelial cells and pericytes cultured on opposing sides of a microporous membrane. Compatibility of the PREDICT96 platform with a variety of quantifiable and scalable assays, including macromolecular permeability, image-based screening, Luminex, and qPCR, is demonstrated. In addition, the bilayer design of the devices allows for channel- or cell type-specific readouts, such as cytokine profiles and gene expression. The microvascular model was responsive to perturbations including barrier disruption, inflammatory stimulation, and fluid shear stress, and our results corroborated the improved robustness of co-culture over endothelial mono-cultures. We anticipate the PREDICT96 platform and adapted assays will be suitable for other complex tissues, including applications to disease models and drug discovery.
Topics: Cell Communication; Cell Membrane Permeability; Cells, Cultured; Coculture Techniques; Dermis; Endothelium, Vascular; Humans; Microfluidic Analytical Techniques; Pericytes; Retina
PubMed: 34108507
DOI: 10.1038/s41598-021-90833-z -
International Journal of Molecular... Dec 2012Human skin is exposed to solar ultraviolet radiation comprising UVB (280-315 nm) and UVA (315-400 nm) on a daily basis. Within the last two decades, the molecular and... (Review)
Review
Human skin is exposed to solar ultraviolet radiation comprising UVB (280-315 nm) and UVA (315-400 nm) on a daily basis. Within the last two decades, the molecular and cellular response to UVA/UVB and the possible effects on human health have been investigated extensively. It is generally accepted that the mutagenic and carcinogenic properties of UVB is due to the direct interaction with DNA. On the other hand, by interaction with non-DNA chromophores as endogenous photosensitizers, UVA induces formation of reactive oxygen species (ROS), which play a pivotal role as mediators of UVA-induced injuries in human skin. This review gives a short overview about relevant findings concerning the molecular mechanisms underlying UVA/UVB-induced cell death. Furthermore, we will highlight the potential role of cutaneous antioxidants and photolabile nitric oxide derivates (NODs) in skin physiology. UVA-induced decomposition of the NODs, like nitrite, leads not only to non-enzymatic formation of nitric oxide (NO), but also to toxic reactive nitrogen species (RNS), like peroxynitrite. Whereas under antioxidative conditions the generation of protective amounts of NO is favored, under oxidative conditions, less injurious reactive nitrogen species are generated, which may enhance UVA-induced cell death.
Topics: Animals; Cell Death; Dermis; Humans; Nitric Oxide; Nitrites; Protective Agents; Ultraviolet Rays
PubMed: 23344028
DOI: 10.3390/ijms14010191 -
Nature Communications Apr 2024Autologous skin grafting is a standard treatment for skin defects such as burns. No artificial skin substitutes are functionally equivalent to autologous skin grafts....
Autologous skin grafting is a standard treatment for skin defects such as burns. No artificial skin substitutes are functionally equivalent to autologous skin grafts. The cultured epidermis lacks the dermis and does not engraft deep wounds. Although reconstituted skin, which consists of cultured epidermal cells on a synthetic dermal substitute, can engraft deep wounds, it requires the wound bed to be well-vascularized and lacks skin appendages. In this study, we successfully generate complete skin grafts with pluripotent stem cell-derived epidermis with appendages on p63 knockout embryos' dermis. Donor pluripotent stem cell-derived keratinocytes encroach the embryos' dermis by eliminating p63 knockout keratinocytes based on cell-extracellular matrix adhesion mediated cell competition. Although the chimeric skin contains allogenic dermis, it is engraftable as long as autologous grafts. Furthermore, we could generate semi-humanized skin segments by human keratinocytes injection into the amnionic cavity of p63 knockout mice embryos. Niche encroachment opens the possibility of human skin graft production in livestock animals.
Topics: Animals; Skin Transplantation; Keratinocytes; Humans; Dermis; Mice, Knockout; Mice; Epidermis; Pluripotent Stem Cells; Skin, Artificial; Epidermal Cells; Extracellular Matrix; Skin
PubMed: 38684678
DOI: 10.1038/s41467-024-47527-7 -
Molecular Systems Biology Aug 2018Murine dermis contains functionally and spatially distinct fibroblast lineages that cease to proliferate in early postnatal life. Here, we propose a model in which a...
Murine dermis contains functionally and spatially distinct fibroblast lineages that cease to proliferate in early postnatal life. Here, we propose a model in which a negative feedback loop between extracellular matrix (ECM) deposition and fibroblast proliferation determines dermal architecture. Virtual-tissue simulations of our model faithfully recapitulate dermal maturation, predicting a loss of spatial segregation of fibroblast lineages and dictating that fibroblast migration is only required for wound healing. To test this, we performed live imaging of dermal fibroblasts, which revealed that homeostatic tissue architecture is achieved without active cell migration. In contrast, both fibroblast proliferation and migration are key determinants of tissue repair following wounding. The results show that tissue-scale coordination is driven by the interdependence of cell proliferation and ECM deposition, paving the way for identifying new therapeutic strategies to enhance skin regeneration.
Topics: Animals; Cell Lineage; Cell Movement; Cell Proliferation; Cells, Cultured; Dermis; Extracellular Matrix; Fibroblasts; Humans; Mice; Skin; Wound Healing
PubMed: 30158243
DOI: 10.15252/msb.20178174 -
Nature Communications Mar 2015Tear resistance is of vital importance in the various functions of skin, especially protection from predatorial attack. Here, we mechanistically quantify the extreme...
Tear resistance is of vital importance in the various functions of skin, especially protection from predatorial attack. Here, we mechanistically quantify the extreme tear resistance of skin and identify the underlying structural features, which lead to its sophisticated failure mechanisms. We explain why it is virtually impossible to propagate a tear in rabbit skin, chosen as a model material for the dermis of vertebrates. We express the deformation in terms of four mechanisms of collagen fibril activity in skin under tensile loading that virtually eliminate the possibility of tearing in pre-notched samples: fibril straightening, fibril reorientation towards the tensile direction, elastic stretching and interfibrillar sliding, all of which contribute to the redistribution of the stresses at the notch tip.
Topics: Animals; Biomechanical Phenomena; Dermis; Elasticity; Fibrillar Collagens; Microscopy, Electron, Scanning; Rabbits; Skin; Stress, Mechanical; Tensile Strength
PubMed: 25812485
DOI: 10.1038/ncomms7649 -
Proceedings of the National Academy of... Jan 2015There is a high mortality in patients with diabetes and severe pressure ulcers. For example, chronic pressure sores of the heels often lead to limb loss in diabetic...
There is a high mortality in patients with diabetes and severe pressure ulcers. For example, chronic pressure sores of the heels often lead to limb loss in diabetic patients. A major factor underlying this is reduced neovascularization caused by impaired activity of the transcription factor hypoxia inducible factor-1 alpha (HIF-1α). In diabetes, HIF-1α function is compromised by a high glucose-induced and reactive oxygen species-mediated modification of its coactivator p300, leading to impaired HIF-1α transactivation. We examined whether local enhancement of HIF-1α activity would improve diabetic wound healing and minimize the severity of diabetic ulcers. To improve HIF-1α activity we designed a transdermal drug delivery system (TDDS) containing the FDA-approved small molecule deferoxamine (DFO), an iron chelator that increases HIF-1α transactivation in diabetes by preventing iron-catalyzed reactive oxygen stress. Applying this TDDS to a pressure-induced ulcer model in diabetic mice, we found that transdermal delivery of DFO significantly improved wound healing. Unexpectedly, prophylactic application of this transdermal delivery system also prevented diabetic ulcer formation. DFO-treated wounds demonstrated increased collagen density, improved neovascularization, and reduction of free radical formation, leading to decreased cell death. These findings suggest that transdermal delivery of DFO provides a targeted means to both prevent ulcer formation and accelerate diabetic wound healing with the potential for rapid clinical translation.
Topics: Administration, Cutaneous; Animals; Apoptosis; Deferoxamine; Dermis; Diabetes Complications; Diabetes Mellitus, Experimental; Drug Delivery Systems; Mice, Inbred C57BL; Necrosis; Neovascularization, Physiologic; Pressure; Reactive Oxygen Species; Stress, Physiological; Ulcer; Vascular Endothelial Growth Factor A; Wound Healing
PubMed: 25535360
DOI: 10.1073/pnas.1413445112