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1.
Nat Commun ; 11(1): 6372, 2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33311516

RESUMO

The thymus is a primary lymphoid organ, essential for T cell maturation and selection. There has been long-standing interest in processes underpinning thymus generation and the potential to manipulate it clinically, because alterations of thymus development or function can result in severe immunodeficiency and autoimmunity. Here, we identify epithelial-mesenchymal hybrid cells, capable of long-term expansion in vitro, and able to reconstitute an anatomic phenocopy of the native thymus, when combined with thymic interstitial cells and a natural decellularised extracellular matrix (ECM) obtained by whole thymus perfusion. This anatomical human thymus reconstruction is functional, as judged by its capacity to support mature T cell development in vivo after transplantation into humanised immunodeficient mice. These findings establish a basis for dissecting the cellular and molecular crosstalk between stroma, ECM and thymocytes, and offer practical prospects for treating congenital and acquired immunological diseases.


Assuntos
Células Estromais , Timo/imunologia , Animais , Autoimunidade , Diferenciação Celular , Células Epiteliais/imunologia , Matriz Extracelular , Feminino , Humanos , Masculino , Camundongos , Camundongos Nus , Ratos , Regeneração , Timócitos , Timo/patologia , Timo/transplante , Alicerces Teciduais
2.
Arch Orthop Trauma Surg ; 137(4): 557-566, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28236186

RESUMO

INTRODUCTION: This case-control study compares patients with healthy elbows to a group of symptomatic patients with cartilage damage/osteoarthritis. MATERIALS AND METHODS: The control group (n = 126) was recruited during routine medical examinations of patients (general medical offices). Included in the case group were a total of 92 patients who were undergoing arthroscopy as a result of chronic elbow discomfort. All patients were questioned with regard to occupational stress and athletic stress. RESULTS: A significantly increased risk of cartilage damage/osteoarthritis was found with subjectively perceived increased stress in occupational settings: OR = 3.8 (95% CI 2.1-6.7); p < 0.001; for the individual stresses of the elbow joint in occupational settings, the following severities in effects were found: Exposure to heavy work OR = 3.9 (95% CI 2.2-6.8); Force OR = 3.7 (95% CI 2.1-6.5); Vibration OR = 4.6 (95% CI 2.5-8.5); Repetition OR = 9.2 (95% CI 3.6-23.3); p < 0.001. Elbow-stressing sport types represent a potential risk factor for the development of cartilage damage/osteoarthritis of the elbow joint: OR = 2.5 (95% CI 1.3-4.7); p = 0.003. CONCLUSIONS: Cartilage damage/radiographic osteoarthritis of the elbow joint are rare with respect to the overall prevalence of osteoarthritis. In the large number of patients with cartilage damage/radiographic osteoarthritis of the elbow joint, occupational or athletic stress factors and injuries sustained, in addition to other causes (rheumatism, gout), can prove as possible causes of these as secondary to symptomatic forms of osteoarthritis.


Assuntos
Doenças das Cartilagens/epidemiologia , Cartilagem Articular/lesões , Articulação do Cotovelo , Exposição Ocupacional/estatística & dados numéricos , Osteoartrite/epidemiologia , Esportes/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Artroscopia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
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