ABSTRACT
Purpose of Study: COVID-19 caused by the SARS-CoV-2 virus has led to a worldwide pandemic with cytokine storm as the leading cause of morbidity and mortality. It is known that pregnant women are at higher risk of viral infections given an alteration in immune response. Mothers who smoke cigarettes during pregnancy are even at higher risk. The infection varies from asymptomatic to severe disease in pregnant women depending upon the degree of inflammation and cytokine storm. At present, limited data are available to show the effects of simultaneous maternal smoking and SARS-CoV-2 infection on the biologic efficacy of human umbilical cord derived mesenchymal stem cells (MSCs). We hypothesized that SARS-CoV-2 infection in combination with smoking of the pregnant mother at the time of delivery will lead to an alteration in the growth and differential potential of cord-derived MSCs. Our aims included collection, isolation and growth of human umbilical cord derived MSCs followed by assessment of their differentiation potential. Methods Used: The study was approved by the Institutional IRB. The umbilical cords were collected from the following groups of pregnant mothers at the time of delivery: Normal (non-smoking and negative SARS-CoV-2 infection), Smoker (smoking with negative SARS-CoV-2), Covid Smoker (smoking with positive SARS-CoV-2 infection) and Covid non-smoker (non-smoking with positive SARS-CoV-2 infection). Plastic adherent cells were harvested from 3 pooled human umbilical cords from each group. These cells were cultured and underwent immunodepletion per International Society for cellular therapy guidelines to isolate MSCs. MSCs were cultured in MSC-culture media to assess the duplication time. Similarly, MSCs were cultured in differentiation media (adipocytes and osteocytes) to assess differentiation time. Summary of Results: Picture shows the duplication and differentiation time from each group. Smoker group showed the longest duplication and differentiation time. Covid non-smoker group showed the shortest duplication and differentiation time. Covid Smoker group showed similar duplication and differentiation time as normal controls. All these results were statistically significant (T-test). Conclusion(s): Maternal smoking and active SARS-CoV-2 infection at the time of delivery alters the growth and differentiation potential of cord-derived MSCs. Further in vitro and in vivo studies are currently in progress to determine how this change effects the biological potential of these cells.
ABSTRACT
Purpose: The field of osteoarthritis (OA) biology is rapidly evolving and brilliant progress has been made this year as well. Methods: Landmark studies of OA biology published in 2021 and early 2022 were selected through PubMed searches and classified by their molecular mechanisms, and it was largely divided into the intra-cellular mechanisms and the inter-compartment or inter-cellular interaction in OA progression. Results: The intra-cellular mechanisms involving OA progression included 1) Piezo1/TRPV4-mediated calcium signaling, 2) low grade inflammation by TLR-CD14-LBP complex and IKKβ-NFkB signaling, 3) PGRN/TNFR2/14-3-3ε/Elk-1 anabolic cascade, 4) G protein-coupled receptor (GPCR) signaling, 5) mechanical loading-cilia/Ift88-hedgehog signaling, 6) mitochondrial fission by ERK1/2-DRP1 pathway, and 7) hypoxia-DOT1L-H3K79 methylation pathway. The studies on inter-compartment or inter-cellular interaction in OA progression included the following subjects: 1) the anabolic role of Lubricin, a proteoglycan from superficial zone cells, 2) osteoclast-chondrocyte interaction via exosomal miRNA and sphingosine 1-phosphate (S1P), 3) αV integrin-mediated TGFβ activation by mechanical loading, 4) TGFβ-mediated suppression of sclerostin in osteocytes, 5) catabolic role of Flightless I as a DAMPs-triggering molecule, and 6) catabolic role of paracrine signaling from fat. Conclusions: Despite the disastrous Covid-19 pandemic situation, many outstanding studies have expanded the boundary of OA biology. They give us not only critical insight on pathophysiology, but also clue for the treatment of OA.
ABSTRACT
The COVID-19 pandemic has evoked the scientific community to combine all efforts needed to find a cure for the disease. With the limited therapeutic effects of pharmacological therapies, attention has been drawn to alternative ones such as stem-cell based therapy particularly with mesenchymal stem cells (MSCs). Recently, a large number of clinical trials are ongoing to evaluate the safety and efficacy of MSCs in patients with COVID-19;however, only very few data are released. Thereby, we anxiously await the results of FDA-approved trials to provide more definitive data on the use of MSCs in COVID-19 patients, especially the critically ill. Herein, we shed light on the therapeutic agents that have been tested and used for the treatment of COVID-19 and provide an insight into MSC-based approaches for COVID-19 at both preclinical and clinical levels.