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Comprehensive Profiling of Secretome Formulations from Fetal- and Perinatal Human Amniotic Fluid Stem Cells
We previously reported that c-KIT+ human amniotic-fluid derived stem cells obtained from leftover samples of routine II trimester prenatal diagnosis (fetal hAFS) are endowed with regenerative paracrine potential driving pro-survival, anti-fibrotic and proliferative effects. hAFS may also be isolated...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038201/ https://www.ncbi.nlm.nih.gov/pubmed/33918297 http://dx.doi.org/10.3390/ijms22073713 |
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author | Costa, Ambra Ceresa, Davide De Palma, Antonella Rossi, Rossana Turturo, Sara Santamaria, Sara Balbi, Carolina Villa, Federico Reverberi, Daniele Cortese, Katia De Biasio, Pierangela Paladini, Dario Coviello, Domenico Ravera, Silvia Malatesta, Paolo Mauri, Pierluigi Quarto, Rodolfo Bollini, Sveva |
author_facet | Costa, Ambra Ceresa, Davide De Palma, Antonella Rossi, Rossana Turturo, Sara Santamaria, Sara Balbi, Carolina Villa, Federico Reverberi, Daniele Cortese, Katia De Biasio, Pierangela Paladini, Dario Coviello, Domenico Ravera, Silvia Malatesta, Paolo Mauri, Pierluigi Quarto, Rodolfo Bollini, Sveva |
author_sort | Costa, Ambra |
collection | PubMed |
description | We previously reported that c-KIT+ human amniotic-fluid derived stem cells obtained from leftover samples of routine II trimester prenatal diagnosis (fetal hAFS) are endowed with regenerative paracrine potential driving pro-survival, anti-fibrotic and proliferative effects. hAFS may also be isolated from III trimester clinical waste samples during scheduled C-sections (perinatal hAFS), thus offering a more easily accessible alternative when compared to fetal hAFS. Nonetheless, little is known about the paracrine profile of perinatal hAFS. Here we provide a detailed characterization of the hAFS total secretome (i.e., the entirety of soluble paracrine factors released by cells in the conditioned medium, hAFS-CM) and the extracellular vesicles (hAFS-EVs) within it, from II trimester fetal- versus III trimester perinatal cells. Fetal- and perinatal hAFS were characterized and subject to hypoxic preconditioning to enhance their paracrine potential. hAFS-CM and hAFS-EV formulations were analyzed for protein and chemokine/cytokine content, and the EV cargo was further investigated by RNA sequencing. The phenotype of fetal- and perinatal hAFS, along with their corresponding secretome formulations, overlapped; yet, fetal hAFS showed immature oxidative phosphorylation activity when compared to perinatal ones. The profiling of their paracrine cargo revealed some differences according to gestational stage and hypoxic preconditioning. Both cell sources provided formulations enriched with neurotrophic, immunomodulatory, anti-fibrotic and endothelial stimulating factors, and the immature fetal hAFS secretome was defined by a more pronounced pro-vasculogenic, regenerative, pro-resolving and anti-aging profile. Small RNA profiling showed microRNA enrichment in both fetal- and perinatal hAFS-EV cargo, with a stably- expressed pro-resolving core as a reference molecular signature. Here we confirm that hAFS represents an appealing source of regenerative paracrine factors; the selection of either fetal or perinatal hAFS secretome formulations for future paracrine therapy should be evaluated considering the specific clinical scenario. |
format | Online Article Text |
id | pubmed-8038201 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-80382012021-04-12 Comprehensive Profiling of Secretome Formulations from Fetal- and Perinatal Human Amniotic Fluid Stem Cells Costa, Ambra Ceresa, Davide De Palma, Antonella Rossi, Rossana Turturo, Sara Santamaria, Sara Balbi, Carolina Villa, Federico Reverberi, Daniele Cortese, Katia De Biasio, Pierangela Paladini, Dario Coviello, Domenico Ravera, Silvia Malatesta, Paolo Mauri, Pierluigi Quarto, Rodolfo Bollini, Sveva Int J Mol Sci Article We previously reported that c-KIT+ human amniotic-fluid derived stem cells obtained from leftover samples of routine II trimester prenatal diagnosis (fetal hAFS) are endowed with regenerative paracrine potential driving pro-survival, anti-fibrotic and proliferative effects. hAFS may also be isolated from III trimester clinical waste samples during scheduled C-sections (perinatal hAFS), thus offering a more easily accessible alternative when compared to fetal hAFS. Nonetheless, little is known about the paracrine profile of perinatal hAFS. Here we provide a detailed characterization of the hAFS total secretome (i.e., the entirety of soluble paracrine factors released by cells in the conditioned medium, hAFS-CM) and the extracellular vesicles (hAFS-EVs) within it, from II trimester fetal- versus III trimester perinatal cells. Fetal- and perinatal hAFS were characterized and subject to hypoxic preconditioning to enhance their paracrine potential. hAFS-CM and hAFS-EV formulations were analyzed for protein and chemokine/cytokine content, and the EV cargo was further investigated by RNA sequencing. The phenotype of fetal- and perinatal hAFS, along with their corresponding secretome formulations, overlapped; yet, fetal hAFS showed immature oxidative phosphorylation activity when compared to perinatal ones. The profiling of their paracrine cargo revealed some differences according to gestational stage and hypoxic preconditioning. Both cell sources provided formulations enriched with neurotrophic, immunomodulatory, anti-fibrotic and endothelial stimulating factors, and the immature fetal hAFS secretome was defined by a more pronounced pro-vasculogenic, regenerative, pro-resolving and anti-aging profile. Small RNA profiling showed microRNA enrichment in both fetal- and perinatal hAFS-EV cargo, with a stably- expressed pro-resolving core as a reference molecular signature. Here we confirm that hAFS represents an appealing source of regenerative paracrine factors; the selection of either fetal or perinatal hAFS secretome formulations for future paracrine therapy should be evaluated considering the specific clinical scenario. MDPI 2021-04-02 /pmc/articles/PMC8038201/ /pubmed/33918297 http://dx.doi.org/10.3390/ijms22073713 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Costa, Ambra Ceresa, Davide De Palma, Antonella Rossi, Rossana Turturo, Sara Santamaria, Sara Balbi, Carolina Villa, Federico Reverberi, Daniele Cortese, Katia De Biasio, Pierangela Paladini, Dario Coviello, Domenico Ravera, Silvia Malatesta, Paolo Mauri, Pierluigi Quarto, Rodolfo Bollini, Sveva Comprehensive Profiling of Secretome Formulations from Fetal- and Perinatal Human Amniotic Fluid Stem Cells |
title | Comprehensive Profiling of Secretome Formulations from Fetal- and Perinatal Human Amniotic Fluid Stem Cells |
title_full | Comprehensive Profiling of Secretome Formulations from Fetal- and Perinatal Human Amniotic Fluid Stem Cells |
title_fullStr | Comprehensive Profiling of Secretome Formulations from Fetal- and Perinatal Human Amniotic Fluid Stem Cells |
title_full_unstemmed | Comprehensive Profiling of Secretome Formulations from Fetal- and Perinatal Human Amniotic Fluid Stem Cells |
title_short | Comprehensive Profiling of Secretome Formulations from Fetal- and Perinatal Human Amniotic Fluid Stem Cells |
title_sort | comprehensive profiling of secretome formulations from fetal- and perinatal human amniotic fluid stem cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038201/ https://www.ncbi.nlm.nih.gov/pubmed/33918297 http://dx.doi.org/10.3390/ijms22073713 |
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