RESUMEN
Pulmonary fibrosis is a progressive disease caused by interstitial inflammation. Treatments are extremely scarce; therapeutic drugs and transplantation therapies are not widely available due to cost and a lack of donors, respectively. Recently, there has been a high interest in regenerative medicine and exponential advancements in stem cell-based therapies have occurred. However, a sensitive imaging technique for investigating the in vivo dynamics of transplanted stem cells has not yet been established and the mechanisms of stem cell-based therapy remain largely unexplored. In this study, we administered mouse adipose tissue-derived mesenchymal stem cells (mASCs) labeled with quantum dots (QDs; 8.0 nM) to a mouse model of bleomycin-induced pulmonary fibrosis in an effort to clarify the relationship between in vivo dynamics and therapeutic efficacy. These QD-labeled mASCs were injected into the trachea of C57BL/6 mice seven days after bleomycin administration to induce fibrosis in the lungs. The therapeutic effects and efficacy were evaluated via in vivo/ex vivo imaging, CT imaging, and H&E staining of lung sections. The QD-labeled mASCs remained in the lungs longer and suppressed fibrosis. The 3D imaging results showed that the transplanted cells accumulated in the peripheral and fibrotic regions of the lungs. These results indicate that mASCs may prevent fibrosis. Thus, QD labeling could be a suitable and sensitive imaging technique for evaluating in vivo kinetics in correlation with the efficacy of cell therapy.
Asunto(s)
Bleomicina , Modelos Animales de Enfermedad , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Ratones Endogámicos C57BL , Fibrosis Pulmonar , Animales , Bleomicina/efectos adversos , Bleomicina/toxicidad , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/diagnóstico por imagen , Fibrosis Pulmonar/terapia , Fibrosis Pulmonar/patología , Ratones , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/citología , Puntos Cuánticos , Pulmón/diagnóstico por imagen , Pulmón/patología , Tomografía Computarizada por Rayos X , Tejido Adiposo/citología , Tejido Adiposo/diagnóstico por imagenRESUMEN
Depressive state is experienced usually in health subjects as "grief" process or "mourning work" in object loss. Also, subthreshold depression (sD) has been found to be a highly prevalent condition, with a considerable impact on the quality of life of patients, resulting in a strongly increased service utilization, and it has been found to be associated with large-scale economic costs because of disability days. A person can be considered to have sD when he or she has clinically relevant depressive symptoms, without meeting criteria for a full-blown major depressive disorder (MDD). The clinically relevant depressive symptoms in sD can either be operationalized as having a depressed mood with one or more additional symptoms of a mood disorder, or as meeting the criteria of minor depression (mD), as defined in the Appendix of the DSM-IV. Assessing the incidence of MDD in patients exhibiting sD is important for several reasons. First, it is an important indicator for the clinical relevance of sD. Secondly, it is important for understanding the process by which an individual develops MDD and the role of depressive symptoms in the process. Thirdly, the increased risk is important because it may provide a rationale for the development of new interventions that prevent the onset of new cases of MDD. Several recent studies in this area have found evidence that it is indeed possible to reduce the number of new cases of MDD by intervening in subjects with sD.