ABSTRACT
Helicobacter cinaedi causes gastroenteritis and bacter-aemia, particularly in immunocompromised individuals. Although cellulitis is sometimes reported to accompany infection by this pathogen, the cutaneous manifestations are poorly understood. To clarify the characteristic cutaneous features, 47 cases of H. cinaedi bacteraemia experienced at Sapporo City General Hospital as nosocomial infection were retrospectively evaluated. Thirty-four percent (16 cases) of the patients showed cutaneous lesions. They all had sudden onset of erythemas accompanied by high temperature. The most common cutaneous manifestations were found to be superficial cellulitis, which results in painful erythemas or infiltrated erythematous plaques on the extremities. These skin lesions can be an early clinical indicator of H. cinaedi bacteraemia in the setting of nosocomial infection.
Subject(s)
Cellulitis/pathology , Cross Infection/pathology , Erythema/pathology , Helicobacter Infections/pathology , Helicobacter/isolation & purification , Skin/pathology , Aged , Anti-Bacterial Agents/therapeutic use , Cellulitis/drug therapy , Cellulitis/microbiology , Cross Infection/drug therapy , Cross Infection/microbiology , Erythema/drug therapy , Erythema/microbiology , Female , Helicobacter/classification , Helicobacter/drug effects , Helicobacter Infections/drug therapy , Helicobacter Infections/microbiology , Humans , Male , Middle Aged , Skin/drug effects , Skin/microbiology , Treatment OutcomeABSTRACT
Attempts to treat congenital protein deficiencies using bone marrow-derived cells have been reported. These efforts have been based on the concepts of stem cell plasticity. However, it is considered more difficult to restore structural proteins than to restore secretory enzymes. This study aims to clarify whether bone marrow transplantation (BMT) treatment can rescue epidermolysis bullosa (EB) caused by defects in keratinocyte structural proteins. BMT treatment of adult collagen XVII (Col17) knockout mice induced donor-derived keratinocytes and Col17 expression associated with the recovery of hemidesmosomal structure and better skin manifestations, as well improving the survival rate. Both hematopoietic and mesenchymal stem cells have the potential to produce Col17 in the BMT treatment model. Furthermore, human cord blood CD34(+) cells also differentiated into keratinocytes and expressed human skin component proteins in transplanted immunocompromised (NOD/SCID/gamma(c)(null)) mice. The current conventional BMT techniques have significant potential as a systemic therapeutic approach for the treatment of human EB.
Subject(s)
Basement Membrane/metabolism , Bone Marrow Transplantation/physiology , Epidermolysis Bullosa/therapy , Membrane Proteins/biosynthesis , Animals , Autoantigens/biosynthesis , Basement Membrane/chemistry , Epidermis , Humans , Keratinocytes/cytology , Mice , Mice, SCID , Non-Fibrillar Collagens/biosynthesis , Non-Fibrillar Collagens/deficiency , Stem Cell Transplantation , Survival Rate , Treatment Outcome , Collagen Type XVIIABSTRACT
Several lines of evidence have demonstrated that various cancers are derived from cancer stem cells (CSCs), which are thought to originate from either tissue stem or progenitor cells. However, recent studies have suggested that the origin of CSCs could be bone marrow-derived cells (BMDCs); for example, gastric cancer, which follows persistent gastric inflammation, appears to originate from BMDCs. Although our previous research showed the capability of BMDCs to differentiate into epidermal keratinocytes, it has yet to be determined whether skin CSCs originate from BMDCs. To assess the possibility that BMDCs could be the origin of CSCs in skin squamous cell carcinoma (SCC), we used a mouse model of UVB-induced skin SCC. We detected a low percentage of BMDCs in the lesions of epidermal dysplasia (0.59%), SCC in situ (0.15%), and SCC (0.03%). Furthermore, we could not find any evidence of clonal BMDC expansion. In SCC lesions, we also found that most of the BMDCs were tumor-infiltrating hematopoietic cells. In addition, BMDCs in the SCC lesions lacked characteristics of epidermal stem cells, including expression of stem cell markers (CD34, high alpha6 integrin) and the potential retention of BrdU label. These results indicate that BMDCs are not a major source of malignant keratinocytes in UVB-induced SCC. Therefore, we conclude that BMDCs are not the origin of CSCs in UVB-induced SCC.
Subject(s)
Bone Marrow Cells/cytology , Carcinoma, Squamous Cell/pathology , Neoplasms, Radiation-Induced/pathology , Neoplastic Stem Cells/cytology , Skin Neoplasms/pathology , Ultraviolet Rays/adverse effects , Animals , Carcinoma, Squamous Cell/etiology , Cell Lineage , Cell Transdifferentiation , Fluorescent Antibody Technique , In Situ Hybridization, Fluorescence , Keratinocytes/cytology , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Skin Neoplasms/etiologySubject(s)
Epstein-Barr Virus Infections/chemically induced , Immunosuppressive Agents/adverse effects , Lymphoma, Large B-Cell, Diffuse/chemically induced , Methotrexate/adverse effects , Skin Neoplasms/chemically induced , Aged , Biomarkers, Tumor/analysis , Biopsy , DNA, Viral/genetics , Epstein-Barr Virus Infections/diagnosis , Epstein-Barr Virus Infections/immunology , Epstein-Barr Virus Infections/virology , Female , Herpesvirus 4, Human/genetics , Humans , Immunocompromised Host , In Situ Hybridization , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/immunology , Lymphoma, Large B-Cell, Diffuse/virology , Male , Middle Aged , Predictive Value of Tests , Risk Factors , Skin Neoplasms/diagnosis , Skin Neoplasms/immunology , Skin Neoplasms/virologySubject(s)
Behcet Syndrome/complications , Myelodysplastic Syndromes/complications , Trisomy , Behcet Syndrome/diagnosis , Behcet Syndrome/drug therapy , Chromosomes, Human, Pair 8 , Fever/etiology , Genital Diseases, Male/etiology , Glucocorticoids/administration & dosage , Humans , Intestinal Diseases/etiology , Male , Middle Aged , Myelodysplastic Syndromes/diagnosis , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/genetics , Skin Ulcer/etiology , Stomatitis, Aphthous/etiology , Treatment OutcomeSubject(s)
Paget Disease, Extramammary/radiotherapy , Pemphigus/etiology , Radiation Injuries/etiology , Skin Neoplasms/radiotherapy , Vulvar Neoplasms/radiotherapy , Administration, Cutaneous , Adrenal Cortex Hormones/administration & dosage , Disease Progression , Female , Humans , Middle Aged , Ointments , Paget Disease, Extramammary/diagnosis , Pemphigus/diagnosis , Pemphigus/drug therapy , Radiation Injuries/diagnosis , Radiation Injuries/drug therapy , Radiotherapy/adverse effects , Recurrence , Remission Induction , Skin Neoplasms/diagnosis , Time Factors , Treatment Outcome , Vulvar Neoplasms/diagnosisSubject(s)
Blister/genetics , Epidermolysis Bullosa/genetics , Ileal Diseases/genetics , Intestinal Obstruction/genetics , Membrane Proteins/genetics , Mutation , Neoplasm Proteins/genetics , Periodontal Diseases/genetics , Photosensitivity Disorders/genetics , Adult , Biopsy , Blister/diagnosis , Blister/therapy , Constriction, Pathologic , DNA Mutational Analysis , Disease Progression , Epidermolysis Bullosa/diagnosis , Epidermolysis Bullosa/therapy , Genetic Predisposition to Disease , Humans , Ileal Diseases/diagnosis , Ileal Diseases/therapy , Ileum/pathology , Immunohistochemistry , Infant, Newborn , Intestinal Mucosa/pathology , Intestinal Obstruction/diagnosis , Intestinal Obstruction/therapy , Male , Periodontal Diseases/diagnosis , Periodontal Diseases/therapy , Phenotype , Photosensitivity Disorders/diagnosis , Photosensitivity Disorders/therapy , Severity of Illness Index , Skin/pathology , Time FactorsSubject(s)
Chlorides/adverse effects , Dental Restoration, Permanent/adverse effects , Dermatitis, Allergic Contact/diagnosis , Dermatitis, Allergic Contact/etiology , Drug Eruptions/diagnosis , Drug Eruptions/etiology , Zinc Compounds/adverse effects , Adrenal Cortex Hormones/therapeutic use , Adult , Chlorides/blood , Dermatitis, Allergic Contact/drug therapy , Disease Progression , Drug Eruptions/drug therapy , Eosinophilia/diagnosis , Eosinophilia/drug therapy , Eosinophilia/etiology , Humans , Male , Patch Tests , Zinc Compounds/bloodSubject(s)
Carcinoma, Squamous Cell/pathology , Ear Auricle/pathology , Head and Neck Neoplasms/pathology , Rhabdoid Tumor/pathology , Aged, 80 and over , Carcinoma, Squamous Cell/surgery , Diagnosis, Differential , Ear Auricle/surgery , Head and Neck Neoplasms/surgery , Hemorrhage , Humans , Male , Rhabdoid Tumor/surgery , Time FactorsSubject(s)
Bowen's Disease/diagnosis , Nail Diseases/virology , Papillomavirus Infections/diagnosis , Pigmentation Disorders/virology , Skin Neoplasms/diagnosis , Adult , Bowen's Disease/virology , DNA, Viral/isolation & purification , Humans , Male , Papillomavirus Infections/genetics , Polymerase Chain Reaction , Skin Neoplasms/virologySubject(s)
Dermatitis, Occupational/diagnosis , Foreign-Body Reaction/diagnosis , Granuloma/diagnosis , Metals, Heavy/adverse effects , Aged , Dermatitis, Occupational/etiology , Dermatitis, Occupational/pathology , Diagnosis, Differential , Foreign-Body Reaction/etiology , Foreign-Body Reaction/pathology , Forestry , Granuloma/etiology , Granuloma/pathology , Humans , Lip/pathology , MaleSubject(s)
Dermoscopy/methods , Keratinocytes/pathology , Skin Diseases/pathology , Adult , Female , Fingers , Humans , Skin Diseases/diagnosis , Skin PigmentationABSTRACT
Mesenchymal stem cells (MSCs) can differentiate not only into mesenchymal lineage cells but also into various other cell lineages. As MSCs can easily be isolated from bone marrow, they can be used in various tissue engineering strategies. In this study, we assessed whether MSCs can differentiate into multiple skin cell types including keratinocytes and contribute to wound repair. First, we found keratin 14-positive cells, presumed to be keratinocytes that transdifferentiated from MSCs in vitro. Next, we assessed whether MSCs can transdifferentiate into multiple skin cell types in vivo. At sites of mouse wounds that had been i.v. injected with MSCs derived from GFP transgenic mice, we detected GFP-positive cells associated with specific markers for keratinocytes, endothelial cells, and pericytes. Because MSCs are predominantly located in bone marrow, we investigated the main MSC recruitment mechanism. MSCs expressed several chemokine receptors; especially CCR7, which is a receptor of SLC/CCL21, that enhanced MSC migration. Finally, MSC-injected mice underwent rapid wound repaired. Furthermore, intradermal injection of SLC/CCL21 increased the migration of MSCs, which resulted in an even greater acceleration of wound repair. Taken together, we have demonstrated that MSCs contribute to wound repair via processes involving MSCs differentiation various cell components of the skin.
Subject(s)
Cell Transdifferentiation , Chemotaxis, Leukocyte , Mesenchymal Stem Cells/pathology , Skin/injuries , Skin/pathology , Wound Healing , Animals , Cell Separation , Cell Transdifferentiation/immunology , Cells, Cultured , Chemotaxis, Leukocyte/immunology , Female , Immunophenotyping , Male , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/immunology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Skin/immunology , Wound Healing/immunologySubject(s)
Hemangiosarcoma/diagnosis , Lung Neoplasms/diagnosis , Skin Neoplasms/diagnosis , Adult , Female , Hemangiosarcoma/complications , Hemangiosarcoma/secondary , Hemangiosarcoma/surgery , Humans , Lung Neoplasms/complications , Lung Neoplasms/secondary , Lung Neoplasms/surgery , Pneumothorax/etiology , Skin Neoplasms/pathology , Young AdultABSTRACT
Recent studies have suggested that bone marrow (BM) cells transdifferentiate to regenerate a variety of cellular lineages. Due to the relatively small population of BM-derived cells in each organ, it is still controversial whether these BM-derived cells are really present in sufficient numbers for effective function. Conversely, it is speculated that chemokine/chemokine receptor interactions mediate this migration of the tissue-specific precursor cells from BM into the target tissue. Here, we show that cutaneous T-cell attracting chemokine (CTACK)/CCL27 is the major regulator involved in the migration of keratinocyte precursor cells from BM into skin. By screening various chemokine expression patterns, we demonstrated that CTACK is constitutively expressed in normal skin and upregulated in wounds and that approximately 20% of CD34(+) BM cells expressed CCR10, the ligand for CTACK. Intradermal injection of CTACK/CCL27 into the periphery of skin wounds significantly enhanced BM-derived keratinocyte (BMDK) migration, and CTACK/CCL27 neutralizing antibody inhibited this BMDK migration. Furthermore, increased BMDK migration caused by CTACK/CCL27 significantly accelerated the wound-healing process without any influence over either angiogenesis or keratinocyte proliferation. These results provide direct evidence that recruitment of BM keratinocyte precursor cells to the skin is regulated by specific chemokine/chemokine receptor interactions, making possible the development of new regenerative therapeutic strategies.
Subject(s)
Bone Marrow Cells/cytology , Chemokines, CC/metabolism , Keratinocytes/cytology , Regeneration , Skin Physiological Phenomena , Skin/cytology , Animals , Antigens, CD34/immunology , Bone Marrow Cells/drug effects , Cell Movement/drug effects , Chemokine CCL21 , Chemokine CCL27 , Chemokine CXCL12 , Chemokines, CC/genetics , Chemokines, CC/pharmacology , Chemokines, CXC/genetics , Chemokines, CXC/metabolism , Chemokines, CXC/pharmacology , Epidermal Cells , Epidermis/drug effects , Keratinocytes/drug effects , Mice , Mice, Inbred C57BL , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, CCR10 , Receptors, CCR7 , Receptors, CXCR4/genetics , Receptors, CXCR4/metabolism , Receptors, Chemokine/genetics , Receptors, Chemokine/metabolism , Regeneration/drug effects , Skin/drug effects , Skin/pathology , Up-Regulation/drug effects , Wound Healing/drug effectsABSTRACT
Angiogenesis, a process by which new vascular networks are formed from pre-existing capillaries, is required for tumors to grow, invade, and metastasize. Vascular endothelial growth factor (VEGF), a specific mitogen to endothelial cells, is a crucial factor for tumor angiogenesis. In this study, we investigated whether minodronate, a newly developed nitrogen-containing bisphosphonate, could inhibit melanoma growth and improve survival in nude mice by suppressing the VEGF signaling. We found here that minodronate inhibited melanoma growth and improved survival in nude mice by suppressing the tumor-associated angiogenesis and macrophage infiltration. Minodronate completely inhibited the VEGF-induced increase in DNA synthesis and tube formation in endothelial cells by suppressing NADPH oxidase-mediated reactive oxygen species generation and Ras activation. Furthermore, minodronate inhibited the VEGF-induced expression of intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 in endothelial cells. Minodronate decreased DNA synthesis and increased apoptotic cell death of cultured melanoma cells as well. Our present study suggests that minodronate might suppress melanoma growth and improve survival in nude mice by two independent mechanisms; one is by blocking the VEGF signaling in endothelial cells, and the other is by inducing apoptotic cell death of melanoma. The present study provides a novel potential therapeutic strategy for the treatment of melanoma.