Marfan syndrome is an autosomal dominant disease of connective tissue caused by mutations in the fibrillin-1 encoding gene FBN1. Patients present cardiovascular, ocular and skeletal manifestations, and although being fully penetrant, MFS is characterized by a wide clinical variability both within and between families. Here we describe a new mouse model of MFS that recapitulates the clinical heterogeneity of the syndrome in humans. Heterozygotes for the mutant Fbn1 allele mgΔloxPneo, carrying the same internal deletion of exons 19–24 as the mgΔ mouse model, present defective microfibrillar deposition, emphysema, deterioration of aortic wall and kyphosis. However, the onset of a clinical phenotypes is earlier in the 129/Sv than in C57BL/6 background, indicating the existence of genetic modifiers of MFS between these two mouse strains. In addition, we characterized a wide clinical variability within the 129/Sv congenic heterozygotes, suggesting involvement of epigenetic factors in disease severity. Finally, we show a strong negative correlation between overall levels of Fbn1 expression and the severity of the phenotypes, corroborating the suggested protective role of normal fibrillin-1 in MFS pathogenesis, and supporting the development of therapies based on increasing Fbn1 expression.

In horses, stem cell therapies are a promising tool to the treatment of many injuries, which are common consequences of athletic endeavor, resulting in high morbidity and often compromising the performance. In spite of many advantages, the isolation of stem cells similar to human, from equine adipose tissue, occurred only recently. The aim of this study was to isolate equine adipose tissue-derived progenitor cells (eAT-PC), to characterize their proliferative potential, and to study their differentiation capacity before and after cryopreservation. The cells, isolated from horse adipose tissue, presented similar fibroblast-like cell morphology in vitro. Their proliferation rate was evaluated during 63 days (23 passages) before and after cryopreservation. After the induction of osteogenic differentiation, von Kossa staining and positive immunostaining studies revealed the formation of calcified extracellular matrix confirming the osteogenic potential of these cells. Adipogenic differentiation was induced using two protocols: routine and other one developed by us, while our protocol requires a shorter time (Oil Red O staining revealed significant accumulation of lipid droplets after 7 days). Chondrogenic differentiation was observed after 21 days of induced pellet culture, as evidenced by histological (toluidine blue) and immunohistochemistry studies. Our data demonstrate that eAT-PC can be easily isolated and successfully expanded in vitro while presenting significant proliferating rate. These cells can be maintained undifferentiated in vitro and can efficiently undergo differentiation at least into mesodermal derivates. These eAT-PC properties were preserved even after cryopreservation. Our findings classify eAT-PC as a promising type of progenitor cells that can be applied in different cell therapies in equines.

hIDPSC showed biological compatibility with the mouse host environment and could survive, proliferate and contribute to the inner cell mass as well as to the trophoblast cell layer after introduction into early mouse embryos (n = 28), which achieved the hatching stage following 24 and 48 h in culture. When transferred to foster mice (n = 5), these blastocysts with hIDPSC (n = 57) yielded embryos (n = 3) and foetuses (n = 6); demonstrating presence of human cells in various organs, such as brain, liver, intestine and hearts, of the human/mouse chimaeras. We verified whether hIDPSC would also be able to differentiate into specific cell types in the mouse environment. Contribution of hIDPSC in at least two types of tissues (muscles and epithelial), was confirmed. We showed that hIDPSC survived, proliferated and differentiated in mouse developing blastocysts and were capable of producing human/mouse chimaeras.

We studied the karyotypes of three hybrid clones of mouse embryonic stem cells and murine splenocytes (two having near diploid and one having near tetraploid chromosome numbers) and the characteristics of their differentiation during the formation of embryoid bodies. The X chromosome originating from embryonic stem cells may be lost in hybrids with a near diploid chromosome number and reprogramming of the "somatic" X may occur. The morphological data we obtained using light and electron microscopy revealed a correlation between the karyotype constitution of hybrid cells and their differentiation during the formation of embryoid bodies. At the beginning of development, the embryoid bodies derived from hybrid cells already showed an advanced degree of differentiation. The production of significant quantities of cartilage was typical for hybrid cells with near tetraploid chromosome numbers. The hybrid cells showed restricted pluripotent capacity and were already committed when they started to differentiate into embryoid bodies.

O tecido adiposo vêm representando uma fonte em potencial para a obtenção de células-tronco mesenquimais (CTMs). Estudos recentes têm demonstrado que as CTMs apresentam potencial de utilização tanto na pesquisa básica como aplicada. Podendo ser obtidas, em grandes quantidades, por meio de anestesia local e com o mínimo de desconforto, as CTMs vêm sendo objeto de intensa pesquisa. Neste estudo, o tecido adiposo de felino, obtido por meio de biópsia realizada na região subcutânea, foi processado de forma a obter uma população celular morfologicamente homogênea. As  células-tronco mesenquimais derivadas do tecido adiposo felinos (CTMs-TAF) foram mantidas, in vitro, em crescimento exponencial até a 9ª passagem apresentando-se como uma população estável e com baixos níveis de senescência. As CTMs-TAF foram capazes de se diferenciarem, in vitro em células adipogênicas, condrogênicas e osteogênicas na presença de factores de indução linhagem específica. Quando injectado em camundongos nude, as CTMs-TAF não foram capazes de dar origem a teratocarcinomas. Estes resultados demonstram de que as CTMs-TAF possuem propriedades que sugerem a sua possível utilização na terapia celular.

Células-tronco mesenquimais no tratamento da pneumonia induzida pelo coronavírus (COVID-19

No abstract

A doença renal crônica (DRC) é uma síndrome caracterizada pelo comprometimento do metabolismo renal, que ocorre de forma dinâmica e progressiva, culminando na perda das funções fisiológicas dos rins. As células progenitoras adultas multipotentes (CPAM), presentes em todos os tecidos que constituem o organismo, têm como caracteríticas principais o seu potencial de autorenovação e diferenciação celular. Quando introduzidas no organismo as CPAM adquirem a morfologia e funcionalidade de qualquer tipo celular que constitui o tecido lesado, o que tem levado a sua utilização terapêutica na medicina veterinária. Neste estudo, sete felinos sem distinção de raça e sexo, com idades entre 4 e 13 anos, acometidos pela DRC estágio 2, foram tratados com células progenitoras adultas multipotentes de tecido adiposo de felinos (CPAMs-TAF), oriundas de um animal doador saudável. Foram realizadas três infusões pela via endovenosa, com intervalo médio de 30 dias. Os pacientes demonstraram uma significativa melhora da função renal após as infusões das CPAMs-TAF sem aparentes efeitos adversos, tendo sido observada uma melhora clínica, ganho de apetite e aumento da disposição já após a primeira aplicação. Conclui-se que a terapia com as CPAMs-TAF colaborou significativamente para a melhoria da qualidade de vida dos felinos acometidos pela DCR estágio 2.