Functional heterogeneity of mesenchymal stem cells and their therapeutic potential in the K18-hACE2 mouse model of SARS-CoV-2 infection
Abstract Background Despite many years of investigation into mesenchymal stem cells (MSCs) and their potential for treating inflammatory conditions such as COVID-19, clinical outcomes remain variable due to factors like donor variability, different tissue sources, and diversity within MSC population...
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BMC
2025-01-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-024-04086-4 |
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| author | Kátia Nunes da Silva Fernanda Martins Marim Gisele Vieira Rocha Zaquer Suzana Munhoz Costa-Ferro Luciana Souza de Aragão França Carolina Kymie Vasques Nonaka Bruno Diaz Paredes Erik Aranha Rossi Erick Correia Loiola Corynne Stephanie Ahouefa Adanho Rachel Santana Cunha Mayck Medeiros Amaral da Silva Fernanda Ferreira Cruz Vivian Vasconcelos Costa Dalila Lucíola Zanette Clarissa Araújo Gurgel Rocha Renato Santana Aguiar Patricia Rieken Macedo Rocco Bruno Solano de Freitas Souza |
| author_facet | Kátia Nunes da Silva Fernanda Martins Marim Gisele Vieira Rocha Zaquer Suzana Munhoz Costa-Ferro Luciana Souza de Aragão França Carolina Kymie Vasques Nonaka Bruno Diaz Paredes Erik Aranha Rossi Erick Correia Loiola Corynne Stephanie Ahouefa Adanho Rachel Santana Cunha Mayck Medeiros Amaral da Silva Fernanda Ferreira Cruz Vivian Vasconcelos Costa Dalila Lucíola Zanette Clarissa Araújo Gurgel Rocha Renato Santana Aguiar Patricia Rieken Macedo Rocco Bruno Solano de Freitas Souza |
| author_sort | Kátia Nunes da Silva |
| collection | DOAJ |
| description | Abstract Background Despite many years of investigation into mesenchymal stem cells (MSCs) and their potential for treating inflammatory conditions such as COVID-19, clinical outcomes remain variable due to factors like donor variability, different tissue sources, and diversity within MSC populations. Variations in MSCs’ secretory and proliferation profiles, and their proteomic and transcriptional characteristics significantly influence their therapeutic potency, highlighting the need for enhanced characterization methods to better predict their efficacy. This study aimed to evaluate the biological characteristics of MSCs from different tissue origins, selecting the most promising line for further validation in a K18-hACE2 mouse model of SARS-CoV-2 infection. Methods We studied nine MSC lines sourced from either bone marrow (hBMMSC), dental pulp (hDPMSC), or umbilical cord tissue (hUCMSC). The cells were assessed for their proliferative capacity, immunophenotype, trilineage differentiation, proteomic profile, and in vitro immunomodulatory potential by co-culture with activated lymphocytes. The most promising MSC line was selected for further experimental validation using the K18-hACE2 mouse model of SARS-CoV-2 infection. Results The analyzed cells met the minimum criteria for defining MSCs, including the expression of surface molecules and differentiation capacity, showing genetic stability and proliferative potential. Proteomic analysis revealed distinct protein profiles that correlate with the tissue origin of MSCs. The immunomodulatory response exhibited variability, lacking a discernible pattern associated with their origin. In co-culture assays with lymphocytes activated with anti-CD3/CD28 beads, all MSC lines demonstrated the ability to inhibit TNF-α, to induce TGF-β and Indoleamine 2,3-dioxygenase (IDO), with varying degrees of inhibition observed for IFN-γ and IL-6, or induction of IL-10 expression. A module of proteins was found to statistically correlate with the potency of IL-6 modulation, leading to the selection of one of the hUCMSCs as the most promising line. Administration of hUCMSC to SARS-CoV-2-infected K18 mice expressing hACE2 was effective in improving lung histology and modulating of a panel of cytokines. Conclusions Our study assessed MSCs derived from various tissues, uncovering significant variability in their characteristics and immunomodulatory capacities. Particularly, hUCMSCs demonstrated potential in mitigating lung pathology in a SARS-CoV-2 infection model, suggesting their promising therapeutic efficacy. |
| format | Article |
| id | doaj-art-c5e8713ddfce46ef8c616810bcff2bd1 |
| institution | Kabale University |
| issn | 1757-6512 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj-art-c5e8713ddfce46ef8c616810bcff2bd12025-01-26T12:18:02ZengBMCStem Cell Research & Therapy1757-65122025-01-0116111710.1186/s13287-024-04086-4Functional heterogeneity of mesenchymal stem cells and their therapeutic potential in the K18-hACE2 mouse model of SARS-CoV-2 infectionKátia Nunes da Silva0Fernanda Martins Marim1Gisele Vieira Rocha2Zaquer Suzana Munhoz Costa-Ferro3Luciana Souza de Aragão França4Carolina Kymie Vasques Nonaka5Bruno Diaz Paredes6Erik Aranha Rossi7Erick Correia Loiola8Corynne Stephanie Ahouefa Adanho9Rachel Santana Cunha10Mayck Medeiros Amaral da Silva11Fernanda Ferreira Cruz12Vivian Vasconcelos Costa13Dalila Lucíola Zanette14Clarissa Araújo Gurgel Rocha15Renato Santana Aguiar16Patricia Rieken Macedo Rocco17Bruno Solano de Freitas Souza18Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ)Department of Genetics, Ecology and Evolution, Institute of Biological Sciences, Universidade Federal de Minas GeraisGonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ)D’Or Institute for Research and Education (IDOR)D’Or Institute for Research and Education (IDOR)D’Or Institute for Research and Education (IDOR)D’Or Institute for Research and Education (IDOR)Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ)Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ)D’Or Institute for Research and Education (IDOR)Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ)Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de JaneiroLaboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de JaneiroDepartment of Morphology, Institute of Biological Sciences, Universidade Federal de Minas GeraisCarlos Chagas Institute, FIOCRUZGonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ)D’Or Institute for Research and Education (IDOR)Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de JaneiroGonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ)Abstract Background Despite many years of investigation into mesenchymal stem cells (MSCs) and their potential for treating inflammatory conditions such as COVID-19, clinical outcomes remain variable due to factors like donor variability, different tissue sources, and diversity within MSC populations. Variations in MSCs’ secretory and proliferation profiles, and their proteomic and transcriptional characteristics significantly influence their therapeutic potency, highlighting the need for enhanced characterization methods to better predict their efficacy. This study aimed to evaluate the biological characteristics of MSCs from different tissue origins, selecting the most promising line for further validation in a K18-hACE2 mouse model of SARS-CoV-2 infection. Methods We studied nine MSC lines sourced from either bone marrow (hBMMSC), dental pulp (hDPMSC), or umbilical cord tissue (hUCMSC). The cells were assessed for their proliferative capacity, immunophenotype, trilineage differentiation, proteomic profile, and in vitro immunomodulatory potential by co-culture with activated lymphocytes. The most promising MSC line was selected for further experimental validation using the K18-hACE2 mouse model of SARS-CoV-2 infection. Results The analyzed cells met the minimum criteria for defining MSCs, including the expression of surface molecules and differentiation capacity, showing genetic stability and proliferative potential. Proteomic analysis revealed distinct protein profiles that correlate with the tissue origin of MSCs. The immunomodulatory response exhibited variability, lacking a discernible pattern associated with their origin. In co-culture assays with lymphocytes activated with anti-CD3/CD28 beads, all MSC lines demonstrated the ability to inhibit TNF-α, to induce TGF-β and Indoleamine 2,3-dioxygenase (IDO), with varying degrees of inhibition observed for IFN-γ and IL-6, or induction of IL-10 expression. A module of proteins was found to statistically correlate with the potency of IL-6 modulation, leading to the selection of one of the hUCMSCs as the most promising line. Administration of hUCMSC to SARS-CoV-2-infected K18 mice expressing hACE2 was effective in improving lung histology and modulating of a panel of cytokines. Conclusions Our study assessed MSCs derived from various tissues, uncovering significant variability in their characteristics and immunomodulatory capacities. Particularly, hUCMSCs demonstrated potential in mitigating lung pathology in a SARS-CoV-2 infection model, suggesting their promising therapeutic efficacy.https://doi.org/10.1186/s13287-024-04086-4Mesenchymal stem cellsHeterogeneityImmunomodulationCOVID-19K18-hACE2 |
| spellingShingle | Kátia Nunes da Silva Fernanda Martins Marim Gisele Vieira Rocha Zaquer Suzana Munhoz Costa-Ferro Luciana Souza de Aragão França Carolina Kymie Vasques Nonaka Bruno Diaz Paredes Erik Aranha Rossi Erick Correia Loiola Corynne Stephanie Ahouefa Adanho Rachel Santana Cunha Mayck Medeiros Amaral da Silva Fernanda Ferreira Cruz Vivian Vasconcelos Costa Dalila Lucíola Zanette Clarissa Araújo Gurgel Rocha Renato Santana Aguiar Patricia Rieken Macedo Rocco Bruno Solano de Freitas Souza Functional heterogeneity of mesenchymal stem cells and their therapeutic potential in the K18-hACE2 mouse model of SARS-CoV-2 infection Stem Cell Research & Therapy Mesenchymal stem cells Heterogeneity Immunomodulation COVID-19 K18-hACE2 |
| title | Functional heterogeneity of mesenchymal stem cells and their therapeutic potential in the K18-hACE2 mouse model of SARS-CoV-2 infection |
| title_full | Functional heterogeneity of mesenchymal stem cells and their therapeutic potential in the K18-hACE2 mouse model of SARS-CoV-2 infection |
| title_fullStr | Functional heterogeneity of mesenchymal stem cells and their therapeutic potential in the K18-hACE2 mouse model of SARS-CoV-2 infection |
| title_full_unstemmed | Functional heterogeneity of mesenchymal stem cells and their therapeutic potential in the K18-hACE2 mouse model of SARS-CoV-2 infection |
| title_short | Functional heterogeneity of mesenchymal stem cells and their therapeutic potential in the K18-hACE2 mouse model of SARS-CoV-2 infection |
| title_sort | functional heterogeneity of mesenchymal stem cells and their therapeutic potential in the k18 hace2 mouse model of sars cov 2 infection |
| topic | Mesenchymal stem cells Heterogeneity Immunomodulation COVID-19 K18-hACE2 |
| url | https://doi.org/10.1186/s13287-024-04086-4 |
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