RESUMO
Despite the advancement of targeted therapy for pulmonary arterial hypertension (PAH), poor prognosis remains a reality. Mesenchymal stem cells (MSCs) are one of the most clinically feasible alternative treatment options. We compared the treatment effects of adipose tissue (AD)-, bone marrow (BD)-, and umbilical cord blood (UCB)-derived MSCs in the rat monocrotaline-induced pulmonary hypertension (PH) model. The greatest improvement in the right ventricular function was observed in the UCB-MSCs treated group. The UCB-MSCs treated group also exhibited the greatest improvement in terms of the largest decrease in the medial wall thickness, perivascular fibrosis, and vascular cell proliferation, as well as the lowest levels of recruitment of innate and adaptive immune cells and associated inflammatory cytokines. Gene expression profiling of lung tissue confirmed that the UCB-MSCs treated group had the most notably attenuated immune and inflammatory profiles. Network analysis further revealed that the UCB-MSCs group had the greatest therapeutic effect in terms of the normalization of all three classical PAH pathways. The intravenous injection of the UCB-MSCs, compared with those of other MSCs, showed superior therapeutic effects in the PH model for the (1) right ventricular function, (2) vascular remodeling, (3) immune/inflammatory profiles, and (4) classical PAH pathways.
Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Transplante de Células-Tronco Mesenquimais , Hipertensão Arterial Pulmonar/terapia , Remodelação Vascular/genética , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Proliferação de Células/genética , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Modelos Animais de Doenças , Regulação da Expressão Gênica/genética , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Hipertensão Arterial Pulmonar/genética , Hipertensão Arterial Pulmonar/patologia , Artéria Pulmonar/crescimento & desenvolvimento , Artéria Pulmonar/patologia , Ratos , Função Ventricular Direita/genéticaAssuntos
Cateterismo Cardíaco/efeitos adversos , Cateterismo Periférico/efeitos adversos , Hematoma/etiologia , Traumatismos dos Nervos Periféricos/etiologia , Artéria Radial/lesões , Nervo Radial/lesões , Neuropatia Radial/etiologia , Lesões do Sistema Vascular/etiologia , Idoso , Angiografia , Cateterismo Cardíaco/métodos , Cateterismo Periférico/métodos , Feminino , Hematoma/diagnóstico por imagem , Humanos , Exame Neurológico , Traumatismos dos Nervos Periféricos/diagnóstico , Traumatismos dos Nervos Periféricos/fisiopatologia , Artéria Radial/diagnóstico por imagem , Nervo Radial/fisiopatologia , Neuropatia Radial/diagnóstico , Neuropatia Radial/fisiopatologia , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento , Lesões do Sistema Vascular/diagnóstico por imagemRESUMO
Cellular uptake of nanoparticles (NPs) depends on the nature of the nanobio system including the solid nanocomponents ( e. g., physicochemical properties of NPs), nanobio interfaces ( e. g., protein corona composition), and the cellular characteristics ( e. g., cell type). In this study, we document the role of sex in cellular uptake of NPs as an "overlooked" factor in nanobio interface investigations. We demonstrate that cell sex leads to differences in NP uptake between male and female human amniotic stem cells (hAMSCs), with greater uptake by female cells. hAMSCs are one of the earliest sources of somatic stem cells. The experiments were replicated with primary fibroblasts isolated from the salivary gland of adult male and female donors of similar ages, and again the extent of NP uptake was altered by cell sex. However, in contrast to hAMSCs, uptake was greater in male cells. We also found out that female versus male amniotic stem cells exhibited different responses to reprogramming into induced pluripotent stem cells (iPSCs) by the Yamanaka factors. Thus, future studies should consider the effect of sex on the nanobio interactions to optimize clinical translation of NPs and iPSC biology and to help researchers to better design and produce safe and efficient therapeutic sex-specific NPs.