| Author | Henriques-Pons, Andrea Henriques | |
| Author | Beghini, Daniela Gois | |
| Author | Silva, Vanessa dos Santos | |
| Author | Horita, Samuel Iwao | |
| Author | Silva, Fabrício Alves Barbosa da | |
| Access date | 2022-07-01T12:12:17Z | |
| Available date | 2022-07-01T12:12:17Z | |
| Document date | 2022 | |
| Citation | HENRIQUE-PONS, Andrea et al. Pulmonary Mesenchymal Stem Cells in Mild Cases of COVID-19 Are Dedicated to Proliferation; In Severe Cases, They Control Inflammation, Make Cell Dispersion, and Tissue Regeneration. Frontiers in Immunology, v. 12, Article 780900, p. 1 - 18, Jan. 2022. | pt_BR |
| ISSN | 1664-3224 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/53607 | |
| Language | eng | pt_BR |
| Publisher | Frontiers Media | pt_BR |
| Rights | open access | pt_BR |
| Subject in Portuguese | COVID-19 | pt_BR |
| Subject in Portuguese | Células-tronco mesenquimais | pt_BR |
| Subject in Portuguese | Terapia celular | pt_BR |
| Subject in Portuguese | Sequenciamento de RNA de célula única | pt_BR |
| Subject in Portuguese | Tempestade de citocinas | pt_BR |
| Title | Pulmonary Mesenchymal Stem Cells in Mild Cases of COVID-19 Are Dedicated to Proliferation; In Severe Cases, They Control Inflammation, Make Cell Dispersion, and Tissue Regeneration | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.3389/fimmu.2021.780900 | |
| Abstract | Mesenchymal stem cells (MSCs) are multipotent adult stem cells present in virtually all
tissues; they have potent self-renewal capacity and differentiate into multiple cell types. For
many reasons, these cells are a promising therapeutic alternative to treat patients with
severe COVID-19 and pulmonary post-COVID sequelae. These cells are not only essential
for tissue regeneration; they can also alter the pulmonary environment through the
paracrine secretion of several mediators. They can control or promote inflammation,
induce other stem cells differentiation, restrain the virus load, and much more. In this work,
we performed single-cell RNA-seq data analysis of MSCs in bronchoalveolar lavage
samples from control individuals and COVID-19 patients with mild and severe clinical
conditions. When we compared samples from mild cases with control individuals, most
genes transcriptionally upregulated in COVID-19 were involved in cell proliferation.
However, a new set of genes with distinct biological functions was upregulated when
we compared severely affected with mild COVID-19 patients. In this analysis, the cells
upregulated genes related to cell dispersion/migration and induced the g-activated
sequence (GAS) genes, probably triggered by IFNGR1 and IFNGR2. Then, IRF-1 was
upregulated, one of the GAS target genes, leading to the interferon-stimulated response
(ISR) and the overexpression of many signature target genes. The MSCs also upregulated
genes involved in the mesenchymal-epithelial transition, virus control, cell chemotaxis, and
used the cytoplasmic RNA danger sensors RIG-1, MDA5, and PKR. In a non-comparative
analysis, we observed that MSCs from severe cases do not express many NF-kB
upstream receptors, such as Toll-like (TLRs) TLR-3, -7, and -8; tumor necrosis factor (TNFR1 or TNFR2), RANK, CD40, and IL-1R1. Indeed, many NF-kB inhibitors were
upregulated, including PPP2CB, OPTN, NFKBIA, and FHL2, suggesting that MSCs do
not play a role in the “cytokine storm” observed. Therefore, lung MSCs in COVID-19 sense
immune danger and act protectively in concert with the pulmonary environment,
confirming their therapeutic potential in cell-based therapy for COVID-19. The
transcription of MSCs senescence markers is discussed. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Programa de Computação Científica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Programa de Computação Científica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Mesenchymal stem cells | pt_BR |
| Subject | COVID-19 | pt_BR |
| Subject | Cell therapy | pt_BR |
| Subject | Single cell RNA sequencing | pt_BR |
| Subject | Cytokine storm | pt_BR |
