ABSTRACT
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.
Subject(s)
Cell- and Tissue-Based Therapy , Mesenchymal Stem Cell Transplantation , Pulmonary Arterial Hypertension/therapy , Vascular Remodeling/genetics , Animals , Bone Marrow Cells/cytology , Bone Marrow Cells/metabolism , Cell Proliferation/genetics , Cord Blood Stem Cell Transplantation , Disease Models, Animal , Gene Expression Regulation/genetics , Humans , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Pulmonary Arterial Hypertension/genetics , Pulmonary Arterial Hypertension/pathology , Pulmonary Artery/growth & development , Pulmonary Artery/pathology , Rats , Ventricular Function, Right/geneticsSubject(s)
Cardiac Catheterization/adverse effects , Catheterization, Peripheral/adverse effects , Hematoma/etiology , Peripheral Nerve Injuries/etiology , Radial Artery/injuries , Radial Nerve/injuries , Radial Neuropathy/etiology , Vascular System Injuries/etiology , Aged , Angiography , Cardiac Catheterization/methods , Catheterization, Peripheral/methods , Female , Hematoma/diagnostic imaging , Humans , Neurologic Examination , Peripheral Nerve Injuries/diagnosis , Peripheral Nerve Injuries/physiopathology , Radial Artery/diagnostic imaging , Radial Nerve/physiopathology , Radial Neuropathy/diagnosis , Radial Neuropathy/physiopathology , Recovery of Function , Time Factors , Treatment Outcome , Vascular System Injuries/diagnostic imagingABSTRACT
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.
