CD146 controls the quality of clinical grade mesenchymal stem cells from human dental pulp

Background Human mesenchymal stem cells from dental pulp (hMSC-DP), including dental pulp stem cells from permanent teeth and exfoliated deciduous teeth, possess unique MSC characteristics such as expression of specific surface molecules and a high proliferation rate. Since hMSC-DP have been applied in numerous clinical studies, it is necessary to establish criteria to evaluate their potency for cell-based therapies. Methods We compared stem cell properties of hMSC-DP at passages 5, 10 and 20 under serum (SE) and serum-free (SF) culture conditions. Cell morphology, proliferation capacity, chromosomal stability, surface phenotypic profiles, differentiation and immunoregulation ability were evaluated. In addition, we assessed surface molecule that regulates hMSC-DP proliferation and immunomodulation. Results hMSC-DP exhibited a decrease in proliferation rate and differentiation potential, as well as a reduced expression of CD146 when cultured under continuous passage conditions. SF culture conditions failed to alter surface marker expression, chromosome stability or proliferation rate when compared to SE culture. SF-cultured hMSC-DP were able to differentiate into osteogenic, adipogenic and neural cells, and displayed the capacity to regulate immune responses. Notably, the expression level of CD146 showed a positive correlation with proliferation, differentiation, and immunomodulation, suggesting that CD146 can serve as a surface molecule to evaluate the potency of hMSC-DP. Mechanistically, we found that CD146 regulates proliferation and immunomodulation of hMSC-DP through the ERK/p-ERK pathway. Conclusion This study indicates that SF-cultured hMSC-DP are appropriate for producing clinical-grade cells. CD146 is a functional surface molecule to assess the potency of hMSC-DP.

SARS-CoV-2 infection studies in lung organoids identify TSPAN8 as novel mediator

SARS coronavirus-2 (SARS-CoV-2) is causing a global pandemic with large variation in COVID-19 disease spectrum. SARS-CoV-2 infection requires host receptor ACE2 on lung epithelium, but epithelial underpinnings of variation are largely unknown. We capitalized on comprehensive organoid assays to report remarkable variation in SARS-CoV-2 infection rates of lung organoids from different subjects. Tropism is highest for TUBA- and MUC5AC-positive organoid cells, but levels of TUBA-, MUC5A-, or ACE2- positive cells do not predict infection rate. We identify surface molecule Tetraspanin 8 (TSPAN8) as novel mediator of SARS-CoV-2 infection, which is not downregulated by this specific virus. TSPAN8 levels, prior to infection, strongly correlate with infection rate and TSPAN8-blocking antibodies diminish SARS-CoV-2 infection. We propose TSPAN8 as novel functional biomarker and potential therapeutic target for COVID-19.

SARS-CoV-2 infection studies in lung organoids identify TSPAN8 as novel mediator

SARS coronavirus-2 (SARS-CoV-2) is causing a global pandemic with large variation in COVID-19 disease spectrum. SARS-CoV-2 infection requires host receptor ACE2 on lung epithelium, but epithelial underpinnings of variation are largely unknown. We capitalized on comprehensive organoid assays to report remarkable variation in SARS-CoV-2 infection rates of lung organoids from different subjects. Tropism is highest for TUBA- and MUC5AC-positive organoid cells, but levels of TUBA-, MUC5A-, or ACE2- positive cells do not predict infection rate. We identify surface molecule Tetraspanin 8 (TSPAN8) as novel mediator of SARS-CoV-2 infection, which is not downregulated by this specific virus. TSPAN8 levels, prior to infection, strongly correlate with infection rate and TSPAN8-blocking antibodies diminish SARS-CoV-2 infection. We propose TSPAN8 as novel functional biomarker and potential therapeutic target for COVID-19.

Repeat-Driven Generation of Antigenic Diversity in a Major Human Pathogen, Trypanosoma cruzi

Trypanosoma cruzi, a zoonotic kinetoplastid protozoan parasite, is the causative agent of American trypanosomiasis (Chagas disease). Having a very plastic, repetitive and complex genome, the parasite displays a highly diverse repertoire of surface molecules, with pivotal roles in cell invasion, immune evasion and pathogenesis. Before 2016, the complexity of the genomic regions containing these genes impaired the assembly of a genome at chromosomal level, making it impossible to study the structure and function of the several thousand repetitive genes encoding the surface molecules of the parasite. We here describe the genome assembly of the Sylvio X10/1 genome sequence, which since 2016 has been used as a reference genome sequence for T. cruzi clade I (TcI), produced using high coverage PacBio single-molecule sequencing. It was used to analyze deep Illumina sequence data from 34 T. cruzi TcI isolates and clones from different geographic locations, sample sources and clinical outcomes. Resolution of the surface molecule gene distribution showed the unusual duality in the organization of the parasite genome, a synteny of the core genomic region with related protozoa flanked by unique and highly plastic multigene family clusters encoding surface antigens. The presence of abundant interspersed retrotransposons in these multigene family clusters suggests that these elements are involved in a recombination mechanism for the generation of antigenic variation and evasion of the host immune response on these TcI strains. The comparative genomic analysis of the cohort of TcI strains revealed multiple cases of such recombination events involving surface molecule genes and has provided new insights into T. cruzi population structure.

Адсорбция атомов бария на карбиде кремния

Adsorption of barium atoms on the C- and Si-faces of the 3C- 6H- and 4H-SiC polytypes is considered within the scope of the Haldane-Anderson model. Charge transfer from Ba atoms to the substrate is analyzed with the account of the band and local states of the adsorbed system. The ionic and metallic con-tributions to the adsorption energy are estimated. To improve some obtained results surface molecule model is used.