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1.
J Cell Mol Med ; 24(17): 9574-9589, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32691511

RESUMO

The tumour mass is composed not only of heterogeneous neoplastic cells, but also a variety of other components that may affect cancer cells behaviour. The lack of detailed knowledge about all the constituents of the tumour microenvironment restricts the design of effective treatments. Nerves have been reported to contribute to the growth and maintenance of numerous tissues. The effects of sensory innervations on tumour growth remain unclear. Here, by using state-of-the-art techniques, including Cre/loxP technologies, confocal microscopy, in vivo-tracing and chemical denervation, we revealed the presence of sensory nerves infiltrating within the melanoma microenvironment, and affecting cancer progression. Strikingly, melanoma growth in vivo was accelerated following genetic ablation or chemical denervation of sensory nerves. In humans, a retrospective analysis of melanoma patients revealed that increased expression of genes related to sensory nerves in tumours was associated with better clinical outcomes. These findings suggest that sensory innervations counteract melanoma progression. The emerging knowledge from this research provides a novel target in the tumour microenvironment for therapeutic benefit in cancer patients.


Assuntos
Melanoma/patologia , Células Receptoras Sensoriais/patologia , Neoplasias Cutâneas/patologia , Animais , Comunicação Celular/fisiologia , Linhagem Celular Tumoral , Progressão da Doença , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Estudos Retrospectivos , Microambiente Tumoral
2.
J Cell Mol Med ; 23(9): 5949-5955, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31278859

RESUMO

Wound healing is a complex dynamic physiological process in response to cutaneous destructive stimuli that aims to restore the cutaneous' barrier role. Deciphering the underlying mechanistic details that contribute to wound healing will create novel therapeutic strategies for skin repair. Recently, by using state-of-the-art technologies, it was revealed that the cutaneous microbiota interact with skin immune cells. Strikingly, commensal Staphylococcus epidermidis-induced CD8+ T cells induce re-epithelization of the skin after injury, accelerating wound closure. From a drug development perspective, the microbiota may provide new therapeutic candidate molecules to accelerate skin healing. Here, we summarize and evaluate recent advances in the understanding of the microbiota in the skin microenvironment.


Assuntos
Microambiente Celular/fisiologia , Pele/crescimento & desenvolvimento , Pele/microbiologia , Staphylococcus epidermidis/fisiologia , Cicatrização/fisiologia , Animais , Linfócitos T CD8-Positivos/imunologia , Microambiente Celular/imunologia , Humanos , Camundongos , Microbiota/imunologia , Pele/imunologia , Neoplasias Cutâneas/patologia , Fenômenos Fisiológicos da Pele , Staphylococcus epidermidis/imunologia
3.
Wound Repair Regen ; 26(5): 392-397, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30098299

RESUMO

Dermal wound healing is the process of repairing and remodeling skin following injury. Delayed or aberrant cutaneous healing poses a challenge for the health care system. The lack of detailed understanding of cellular and molecular mechanisms involved in this process hampers the development of effective targeted treatments. In a recent study, Parfejevs et al.-using state-of-the-art technologies, including in vivo sophisticated Cre/loxP techniques in combination with a mouse model of excisional cutaneous wounding-reveal that Schwann cells induce adult dermal wound healing. Strikingly, genetic ablation of Schwann cells delays wound contraction and closure, decreases myofibroblast formation, and impairs skin re-epithelization after injury. From a drug development perspective, Schwann cells are a new cellular candidate to be activated to accelerate skin healing. Here, we summarize and evaluate recent advances in the understanding of Schwann cells roles in the skin microenvironment.


Assuntos
Células de Schwann/fisiologia , Pele/lesões , Cicatrização/fisiologia , Ferimentos e Lesões/patologia , Animais , Diferenciação Celular/fisiologia , Células Cultivadas , Modelos Animais de Doenças , Camundongos , Receptor Cross-Talk , Pele/patologia
4.
Stem Cell Rev Rep ; 13(5): 567-574, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28669077

RESUMO

Platelets are released from megakaryocytes. The bone marrow has been proposed to be the major site where this process occurs. Lefrançais et al. (2017) using state-of-the-art techniques including two-photon microscopy, in vivo lineage-tracing technologies, and sophisticated lung transplants reveal that the lung is also a primary site for platelet biogenesis. Strikingly, lung megakaryocytes can completely reconstitute platelet counts in the blood in mice with thrombocytopenia. This study also shows that hematopoietic progenitors, with capacity to repopulate the bone marrow after irradiation, are present in the lungs. This work brings a novel unexpected role for the lung as a niche for hematopoiesis. The emerging knowledge from this research may be important for the treatment of several disorders.


Assuntos
Plaquetas/citologia , Células-Tronco Hematopoéticas/citologia , Pulmão/citologia , Megacariócitos/citologia , Nicho de Células-Tronco/fisiologia , Animais , Plaquetas/fisiologia , Células da Medula Óssea/citologia , Células da Medula Óssea/fisiologia , Contagem de Células , Diferenciação Celular , Modelos Animais de Doenças , Hematopoese/fisiologia , Células-Tronco Hematopoéticas/fisiologia , Humanos , Pulmão/fisiologia , Pulmão/cirurgia , Transplante de Pulmão , Megacariócitos/fisiologia , Camundongos , Trombocitopenia/tratamento farmacológico , Trombocitopenia/patologia , Trombocitopenia/fisiopatologia , Trombopoetina/uso terapêutico
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