Patients with coronavirus disease 2019 (COVID-19) have a wide variety of clinical outcomes ranging from asymptomatic to severe respiratory syndrome that can progress to life-threatening lung lesions. The identification of prognostic factors can help to improve the risk stratification of patients by promptly defining for each the most effective therapy to resolve the disease. The etiological agent causing COVID-19 is a new coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that enters cells via the ACE2 receptor. SARS-CoV-2 infection causes a reduction in ACE2 levels, leading to an imbalance in the renin–angiotensin system (RAS), and consequently, in blood pressure and systemic vascular resistance. ERAP1 and ERAP2 are two RAS regulators and key components of MHC class I antigen processing. Their polymorphisms have been associated with autoimmune and inflammatory conditions, hypertension, and cancer. Based on their involvement in the RAS, we believe that the dysfunctional status of ERAP1 and ERAP2 enzymes may exacerbate the effect of SARS-CoV-2 infection, aggravating the symptomatology and clinical outcome of the disease. In this review, we discuss this hypothesis.
Background: Since the esophagus has no redundancy, congenital and acquired esophageal diseases often require esophageal substitution, with complicated surgery and intestinal or gastric transposition. Peri-and-post-operative complications are frequent, with major problems related to the food transit and reflux. During the last years tissue engineering products became an interesting therapeutic alternative for esophageal replacement, since they could mimic the organ structure and potentially help to restore the native functions and physiology. The use of acellular matrices pre-seeded with cells showed promising results for esophageal replacement approaches, but cell homing and adhesion to the scaffold remain an important issue and were investigated. Methods: A porcine esophageal substitute constituted of a decellularized scaffold seeded with autologous bone marrow-derived mesenchymal stromal cells (BM-MSCs) was developed. In order to improve cell seeding and distribution throughout the scaffolds, they were micro-perforated by Quantum Molecular Resonance (QMR) technology (Telea Electronic Engineering). Results: The treatment created a microporous network and cells were able to colonize both outer and inner layers of the scaffolds. Non seeded (NSS) and BM-MSCs seeded scaffolds (SS) were implanted on the thoracic esophagus of 4 and 8 pigs respectively, substituting only the muscle layer in a mucosal sparing technique. After 3 months from surgery, we observed an esophageal substenosis in 2/4 NSS pigs and in 6/8 SS pigs and a non-practicable stricture in 1/4 NSS pigs and 2/8 SS pigs. All the animals exhibited a normal weight increase, except one case in the SS group. Actin and desmin staining of the post-implant scaffolds evidenced the regeneration of a muscular layer from one anastomosis to another in the SS group but not in the NSS one. Conclusions: A muscle esophageal substitute starting from a porcine scaffold was developed and it was fully repopulated by BM-MSCs after seeding. The substitute was able to recapitulate in shape and function the original esophageal muscle layer.
Cleft lip and palate (CL/P) is the most prevalent craniofacial birth defect in humans. None of the surgical procedures currently used for CL/P repair lead to definitive correction of hard palate bone interruption. Advances in tissue engineering and regenerative medicine aim to develop new strategies to restore palatal bone interruption by using tissue or organ-decellularized bioscaffolds seeded with host cells. Aim of this study was to set up a new natural scaffold deriving from a decellularized porcine mucoperiosteum, engineered by an innovative micro-perforation procedure based on Quantum Molecular Resonance (QMR) and then subjected to in vitro recellularization with human bone marrow-derived mesenchymal stem cells (hBM-MSCs). Our results demonstrated the efficiency of decellularization treatment gaining a natural, non-immunogenic scaffold with preserved collagen microenvironment that displays a favorable support to hMSC engraftment, spreading and differentiation. Ultrastructural analysis showed that the micro-perforation procedure preserved the collagen mesh, increasing the osteoinductive potential for mesenchymal precursor cells. In conclusion, we developed a novel tissue engineering protocol to obtain a non-immunogenic mucoperiosteal scaffold suitable for allogenic transplantation and CL/P repair. The innovative micro-perforation procedure improving hMSC osteogenic differentiation potentially impacts for enhanced palatal bone regeneration leading to future clinical applications in humans.
Background: b-globin gene transfer can modulate and may even correct the clinical expression of sickle cell disease (SCD). LentiGlobin gene therapy (GT) contains autologous CD34+ haematopoietic stem cells (HSCs) transduced with the BB305 lentiviral vector (LVV), which encodes b-globin with an anti-sickling substitution (HbA T87Q ). In 7 patients with severe SCD treated with LentiGlobin GT in the Phase 1/2, HGB-206 study (NCT02140554) under the original protocol and with drug product (DP) made from bone marrow harvested (BMH) HSCs (Group A, fully enrolled), HbA T87Q production was stable, but suboptimal. The protocol was revised to include pre-harvest red blood cell (RBC) transfusions, higher target busulfan levels, and refined DP manufacturing (Group B, fully enrolled). Patients in Group C were treated under the revised protocol and with DPs made from plerixafor-mobilised HSCs. Aims: To describe the safety and efficacy of LentiGlobin GT in Group C patients in the ongoing HGB-206 study. Methods: Adults with severe SCD (history of recurrent vaso-occlusive crisis, acute chest syndrome, stroke, or tricuspid regurgitant jet velocity of >2.5 m/s) were enrolled. Before HSC collection, patients in Group C received 2 months of RBC transfusions, targeting Hb of 10 -12 g/dL and HbS <30% of total Hb. CD34+ HSCs were collected by aphaeresis 4 -6 hours post 240 microg/kg plerixafor and transduced with the BB305 LVV. After myeloablative busulfan, DP was infused and patients were monitored for adverse events (AEs), engraftment, HbA T87Q levels, and haemolysis markers. Summary statistics are median (min -max). Results: Nine Group C patients (25 [19 -35] years old) were treated with LentiGlobin GT as of 14 Sep 2018, with 5.2 (0.5 -9.2) months of follow-up. The DP vector copy number was 3.8 (2.8 -5.6) copies/diploid genome and cell dose was 6.5 (3 -8) x10 6 CD34+ cells/kg, with 81 (68 -90) % CD34+ cells transduced. As of 14 Sep 2018, 8 and 7 patients achieved neutrophil and platelet engraftment, at 20 (18 -24) and 28 (19 -136) days, respectively. Febrile neutropenia (n = 6) and stomatitis (n = 6) were the most common non-haematologic Grade 3 AEs post DP infusion. No DP-related AEs, AEs of veno-occlusive liver disease, or graft failure were reported. Early data show no clonal dominance or vector-mediated replication competent lentivirus. There were no vaso-occlusive events post DP infusion as of datacut date. In 8 patients with 1 month follow-up, median HbA T87Q at last visit was 4.6 (2.5 -8.2) g/dL. At last visit in 4 patients with 6 months follow-up, total Hb was 9.9 -13.7 g/dL without RBC transfusions, with 47 -60% comprised of HbA T87Q , which nearly equalled or exceeded HbS levels (38 -49% of total Hb). Baseline reticulocyte counts, total bilirubin, and lactate dehydrogenase were 380 (349 -415) x10 9 /L (n = 4), 56 (29 -86) micromol/L (n = 9), and 354 (226 -738) U/L (n = 7), and at last visit decreased by a median of 64%, 70%, and 45%, respectively.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.