Placental inflammation in a fetal demise of a SARS-CoV-2-asymptomatic, COVID-19-unvaccinated pregnant woman: a case-report.

BACKGROUND: Intrauterine fetal demise is a recognized complication of coronavirus disease 2019 in pregnant women and is associated with histopathological placental lesions. The pathological mechanism and virus-induced immune response in the placenta are not fully understood. A detailed description of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced inflammation in the placenta during fetal demise is crucial for improved clinical management. CASE PRESENTATION: We report the case of a 27-week gestation SARS-CoV-2-asymptomatic unvaccinated pregnant woman without comorbidities or other risk factors for negative pregnancy outcomes with a diagnosis of intrauterine fetal demise. Histopathological findings corresponded to patterns of subacute inflammation throughout the anatomic compartments of the placenta, showing severe chorioamnionitis, chronic villitis and deciduitis, accompanied by maternal and fetal vascular malperfusion. Our immunohistochemistry results revealed infiltration of CD68+ macrophages, CD56+ Natural Killer cells and scarce CD8+ T cytotoxic lymphocytes at the site of placental inflammation, with the SARS-CoV-2 nucleocapsid located in stromal cells of the chorion and chorionic villi, and in decidual cells. CONCLUSION: This case describes novel histopathological lesions of inflammation with infiltration of plasma cells, neutrophils, macrophages, and natural killer cells associated with malperfusion in the placenta of a SARS-CoV-2-infected asymptomatic woman with intrauterine fetal demise. A better understanding of the inflammatory effects exerted by SARS-CoV-2 in the placenta will enable strategies for better clinical management of pregnant women unvaccinated for SARS-CoV-2 to avoid fatal fetal outcomes during future transmission waves.

Increased proliferation and differentiation capacity of placenta-derived mesenchymal stem cells from women of median maternal age correlates with telomere shortening.

Mesenchymal stem cells (MSCs) experience functional decline with systemic aging, resulting in reduced proliferation, increased senescence, and lower differentiation potential. The placenta represents a valuable source of MSCs, but the possible effect of donor age on the properties of placenta-derived mesenchymal stem cells (PDMSCs) has not been thoroughly studied. Thus, the aim of this study was to underscore the effect of maternal age on the biological characteristics and stemness properties of PDMSCs. PDMSCs were isolated from 5 donor age groups (A: 18-21, B: 22-25, C: 26-30, D:31-35 and E: ≥36 years) for comparison of morphological, proliferative and differentiation properties. The pluripotency markers NANOG, OCT4, and SSEA4, as well as multipotency and differentiation markers, showed higher expression in PDMSCs from mothers aged 22-35 years, with up to a 7-fold increase in adipogenesis. Cumulative population doubling, cell growth curves, and colony-forming unit-fibroblast assays revealed higher self-renewal ability in donors 26-30 years old. An increase in the proliferative characteristics of PDMSCs correlated with increased telomere shortening, suggesting that shorter telomere lengths could be related to cellular division rather than aging. A clear understanding of the effect of maternal age on MSC regenerative potential will assist in increasing the effectiveness of future cell therapies.

Capacidad multipotencial en células madre mesenquimales derivadas de la placenta humana en Panamá / Multipotent capacity of human placenta­derived mesenchymal stem cells in Panama

Introducción: Las células madre mesenquimales (MSCs) tienen la capacidad única de auto­renovación y pluripotencia con la cual apoyan en la regeneración de tejidos en or­ ganismos vivos. El mayor potencial terapéutico de las MSCs derivadas de la placenta (PDMSCs) humana, como fuente más joven de MSCs, estimula la búsqueda de las me­ jores condiciones de cultivo que preserven su capacidad de proliferar y diferenciarse. Sin embargo, estudios relacionados a la caracterización de la multipotencialidad de las PDMSCs durante periodos prolongados de cultivo, no han sido reportados en Panamá. Por lo tanto, el objetivo de este estudio fue el de implementar un proceso de aislamiento y cultivo que preserve las propiedades multipotentes en PDMSCs. Materiales y Méto­ dos: Placentas humanas a término completo fueron obtenidas para el aislamiento de las MSCs. Las PDMSCs fueron caracterizadas según su morfología, expresión positiva de marcadores CD90, CD73, CD105, y capacidad de proliferación y diferenciación a linajes mesodérmicos. Resultados: Se ha demostrado la obtención de poblaciones de PDMSCs con morfología fibroblástica, adherencia plástica, expresión positiva de los marcadores CD90, CD73 y CD105, y capacidad de diferenciación osteogénica, adi­ pogénica y condrogénica. Posterior al aislamiento y crio­preservación, las PDMSCs mantuvieron una viabilidad mayor de 95%, una tasa de proliferación por más de 40 días en cultivo, y la expresión positiva de los marcadores CD90, CD73, y CD105 al pasaje 16. Conclusión: Nuestros resultados demuestran una metodología eficiente para obten­ ción y cultivo de PDMSCs que mantienen sus características multipotentes durante períodos prolongados de cultivo, abriendo el camino para futuras terapias celulares

ntroduction: Human mesenchymal stem cells are (MSCs) unique in their pluripotency and their ability to self­renew in order to support tissue regeneration in living organisms. The increased therapeutic potential of PDMSCs as a pool of younger MSCs with a vast capacity for expansion, minor predisposition for tumor formation or immune reactions spurs the search for the best culture conditions to preserve their ability to differentiate and proliferate. However, studies regarding characterization of multipotent isolated PDMSCs during prolonged periods of culture has not been reported thus far in Panama. Therefore, in this study we seek to implement isolation and culture procedures that pre­ serve multipotent characteristics in PDMSCs. Materials and Methods: Full­term human placentas were obtained for the isolation of MSCs. PDMSCs where characterized based on their morphology, positive expression of CD90, CD73, and CD105, and their ability to proliferate and differentiate to mesodermal lineages. Results: It was demonstrated that our isolated PDMSCs presented the MSC characteristics of fibroblastic morphology, plastic adherence, positive expression of CD90, CD73, and CD105 markers, as well as osteogenesis, adipogenesis, and osteogenic differentiation ability. When PDMSCs were cultured after isolation or cryopreservation, viability was maintained above 95%, with their proliferation rate maintained after 40 days, and positive expression of CD90, CD73, and CD105 markers kept after 16 passages. Conclusion: Taken together, our results de­ monstrated a methodology to obtain successful source of isolated human PDMSCs that kept their multipotent properties over time, opening the path for future cellular therapies.