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Over the last few years, there has been an increased interest in the study of stem cells in biomedicine for therapeutic use and as a source for healing diseased or injured organs/tissues. More recently, vibrational spectroscopy has been applied to study stem cell differentiation. In this study, we have used both synchrotron based FTIR and Raman microspectroscopies to assess possible differences between human pluripotent (embryonic) and multipotent (adult mesenchymal) stem cells, and how O2concentration in cell culture could affect the spectral signatures of these cells. Our work shows that infrared spectroscopy of embryonic (pluripotent) and adult mesenchymal (multipotent) stem cells have different spectral signatures based on the amount of lipids in their cytoplasm (confirmed with cytological staining). Furthermore, O2concentration in cell culture causes changes in both the FTIR and Raman spectra of embryonic stem cells. These results show that embryonic stem cells might be more sensitive to O2concentration when compared to mesenchymal stem cells. While vibrational spectroscopy could therefore be of potential use in identifying different populations of stem cells further work is required to better understand these differences. [ABSTRACT FROM AUTHOR]

Abstract Background Coronavirus disease 2019 (COVID-19) has created a global pandemic with significant morbidity and mortality. SARS-CoV-2 primarily infects the lungs and is associated with various organ complications. Therapeutic approaches to combat COVID-19, including convalescent plasma and vaccination, have been developed. However, the high mutation rate of SARS-CoV-2 and its ability to inhibit host T-cell activity pose challenges for effective treatment. Mesenchymal stem cells (MSCs) and their extracellular vesicles (MSCs–EVs) have shown promise in COVID-19 therapy because of their immunomodulatory and regenerative properties. MicroRNAs (miRNAs) play crucial regulatory roles in various biological processes and can be manipulated for therapeutic purposes. Objective We aimed to investigate the role of lyophilized MSC–EVs and their microRNAs in targeting the receptors involved in SARS-CoV-2 entry into host cells as a strategy to limit infection. In silico microRNA prediction, structural predictions of the microRNA–mRNA duplex, and molecular docking with the Argonaut protein were performed. Methods Male Syrian hamsters infected with SARS-CoV-2 were treated with human Wharton’s jelly-derived Mesenchymal Stem cell-derived lyophilized exosomes (Bioluga Company)via intraperitoneal injection, and viral shedding was assessed. The potential therapeutic effects of MSCs–EVs were measured via histopathology of lung tissues and PCR for microRNAs. Results The results revealed strong binding potential between miRNA‒mRNA duplexes and the AGO protein via molecular docking. MSCs–EVs reduced inflammation markers and normalized blood indices via the suppression of viral entry by regulating ACE2 and TMPRSS2 expression. MSCs–EVs alleviated histopathological aberrations. They improved lung histology and reduced collagen fiber deposition in infected lungs. Conclusion We demonstrated that MSCs–EVs are a potential therapeutic option for treating COVID-19 by preventing viral entry into host cells.

Alzheimer's disease (AD) is a devastating neurological condition characterized by cognitive decline, motor coordination impairment, and amyloid plaque accumulation. The underlying molecular mechanisms involve oxidative stress, inflammation, and neuronal degeneration. This study aimed to investigate the therapeutic effects of mesenchymal stem cell-derived exosomes (MSC-exos) on AD and explore the molecular pathways involved, including the PI3K/Akt/mTOR axis, autophagy, and neuroinflammation. To assess the potential of MSC-exos for the treatment of AD, rats were treated with AlCl3 (17 mg/kg/once/day) for 8 weeks, followed by the administration of an autophagy activator (rapamycin), or MSC-exos with or without an autophagy inhibitor (3-methyladenin; 3-MA+ chloroquine) for 4 weeks. Memory impairment was tested, and brain tissues were collected for gene expression analyses, western blotting, histological studies, immunohistochemistry, and transmission electron microscopy. Remarkably, the administration of MSC-exos improved memory performance in AD rats and reduced the accumulation of amyloid-beta (Aβ) plaques and tau phosphorylation. Furthermore, MSC-exos promoted neurogenesis, enhanced synaptic function, and mitigated astrogliosis in AD brain tissues. These beneficial effects were associated with the modulation of autophagy and the PI3K/Akt/mTOR signalling pathway, as well as the inhibition of neuroinflammation. Additionally, MSC-exos were found to regulate specific microRNAs, including miRNA-21, miRNA-155, miRNA-17–5p, and miRNA-126–3p, further supporting their therapeutic potential. Histopathological and bioinformatic analyses confirmed these findings. This study provides compelling evidence that MSC-exos hold promise as a potential therapeutic approach for AD. By modulating the PI3K/Akt/mTOR axis, autophagy, and neuroinflammation, MSC-exos have the potential to improve memory, reduce Aβ accumulation, enhance neurogenesis, and mitigate astrogliosis. These findings shed light on the therapeutic potential of MSC-exos and highlight their role in combating AD.

Background. Liver transplantation remains the only viable therapy for liver failure but has a severely restricted utility. Here, we aimed to decellularize rat livers to form acellular 3D bio-scaffolds suitable for seeding with induced pluripotent cells (iPSCs) as a tool to investigate the role of Wnt/β-catenin signaling in liver development and generation. Methods. Dissected rat livers were randomly divided into three groups: I (control); II (decellularized scaffolds) and III (recellularized scaffolds). Liver decellularization was established via an adapted perfusion procedure and assessed through the measurement of extracellular matrix (ECM) proteins and DNA content. Liver recellularization was assessed through histological examination and measurement of transcript levels of Wnt/β-catenin pathway, hepatogenesis, liver-specific microRNAs and growth factors essential for liver development. Adult rat liver decellularization was confirmed by the maintenance of ECM proteins and persistence of growth factors essential for liver regeneration. Results. iPSCs seeded rat decellularized livers displayed upregulated transcript expression of Wnt/β-catenin pathway-related, growth factors, and liver specification genes. Further, recellularized livers displayed restored liver-specific functions including albumin secretion and urea synthesis. Conclusion. This establishes proof-of-principle for the generation of three-dimensional liver organ scaffolds as grafts and functional re-establishment.