Uncovering the secretome of mesenchymal stromal cells exposed to healthy, traumatic, and degenerative intervertebral discs: a proteomic analysis
Abstract Background Mesenchymal stromal cells (MSCs) have been introduced as promising cell source for regenerative medicine. Besides their multilineage differentiation capacity, MSCs release a wide spectrum of bioactive factors. This secretome holds immunomodulatory and regenerative capacities. In...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-01-01
|
| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-020-02062-2 |
| _version_ | 1818645273769934848 |
|---|---|
| author | Sebastian Wangler Amir Kamali Christina Wapp Karin Wuertz-Kozak Sonja Häckel Claudia Fortes Lorin M. Benneker Lisbet Haglund R. Geoff Richards Mauro Alini Marianna Peroglio Sibylle Grad |
| author_facet | Sebastian Wangler Amir Kamali Christina Wapp Karin Wuertz-Kozak Sonja Häckel Claudia Fortes Lorin M. Benneker Lisbet Haglund R. Geoff Richards Mauro Alini Marianna Peroglio Sibylle Grad |
| author_sort | Sebastian Wangler |
| collection | DOAJ |
| description | Abstract Background Mesenchymal stromal cells (MSCs) have been introduced as promising cell source for regenerative medicine. Besides their multilineage differentiation capacity, MSCs release a wide spectrum of bioactive factors. This secretome holds immunomodulatory and regenerative capacities. In intervertebral disc (IVD) cells, application of MSC secretome has been shown to decrease the apoptosis rate, induce proliferation, and promote production of extracellular matrix (ECM). For clinical translation of secretome-based treatment, characterization of the secretome composition is needed to better understand the induced biological processes and identify potentially effective secretomes. Methods This study aimed to investigate the proteome released by bone marrow-derived MSCs following exposure to a healthy, traumatic, or degenerative human IVD environment by mass spectroscopy and quantitative immunoassay analyses. Exposure of MSCs to the proinflammatory stimulus interleukin 1β (IL-1β) was used as control. Results Compared to MSC baseline secretome, there were 224 significantly up- or downregulated proteins following healthy, 179 following traumatic, 223 following degenerative IVD, and 160 proteins following IL-1β stimulus. Stimulation of MSCs with IVD conditioned media induced a more complex MSC secretome, involving more biological processes, compared to stimulation with IL-1β. The MSC response to stimulation with IVD conditioned medium was dependent on their pathological status. Conclusions The MSC secretome seemed to match the primary need of the IVD: homeostasis maintenance in the case of healthy IVDs, versus immunomodulation, adjustment of ECM synthesis and degradation disbalance, and ECM (re) organization in the case of traumatic and degenerative IVDs. These findings highlight the importance of cell preconditioning in the development of tailored secretome therapies. Graphical abstract The secretome of human bone marrow-derived mesenchymal stromal cells (MSCs) stimulated with intervertebral disc (IVD) conditioned medium was analyzed by proteomic profiling. Depending on the pathological state of the IVD, the MSC secretome protein composition indicated immunomodulatory or anabolic activity of the secretome. These findings may have implications for tailored secretome therapy for the IVD and other tissues. |
| first_indexed | 2024-12-17T00:28:08Z |
| format | Article |
| id | doaj.art-551e31bf59da4333ab7f99de8fefbbf6 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-17T00:28:08Z |
| publishDate | 2021-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-551e31bf59da4333ab7f99de8fefbbf62022-12-21T22:10:25ZengBMCStem Cell Research & Therapy1757-65122021-01-0112111710.1186/s13287-020-02062-2Uncovering the secretome of mesenchymal stromal cells exposed to healthy, traumatic, and degenerative intervertebral discs: a proteomic analysisSebastian Wangler0Amir Kamali1Christina Wapp2Karin Wuertz-Kozak3Sonja Häckel4Claudia Fortes5Lorin M. Benneker6Lisbet Haglund7R. Geoff Richards8Mauro Alini9Marianna Peroglio10Sibylle Grad11AO Research Institute DavosAO Research Institute DavosAO Research Institute DavosDepartment of Health Sciences and Technology, ETH ZurichDepartment of Orthopaedic Surgery and Traumatology, Inselspital, Bern University Hospital, University of BernFunctional Genomics Center ZurichDepartment of Orthopaedic Surgery and Traumatology, Inselspital, Bern University Hospital, University of BernDepartment of Surgery, Division of Orthopaedics, Faculty of Medicine, McGill UniversityAO Research Institute DavosAO Research Institute DavosAO Research Institute DavosAO Research Institute DavosAbstract Background Mesenchymal stromal cells (MSCs) have been introduced as promising cell source for regenerative medicine. Besides their multilineage differentiation capacity, MSCs release a wide spectrum of bioactive factors. This secretome holds immunomodulatory and regenerative capacities. In intervertebral disc (IVD) cells, application of MSC secretome has been shown to decrease the apoptosis rate, induce proliferation, and promote production of extracellular matrix (ECM). For clinical translation of secretome-based treatment, characterization of the secretome composition is needed to better understand the induced biological processes and identify potentially effective secretomes. Methods This study aimed to investigate the proteome released by bone marrow-derived MSCs following exposure to a healthy, traumatic, or degenerative human IVD environment by mass spectroscopy and quantitative immunoassay analyses. Exposure of MSCs to the proinflammatory stimulus interleukin 1β (IL-1β) was used as control. Results Compared to MSC baseline secretome, there were 224 significantly up- or downregulated proteins following healthy, 179 following traumatic, 223 following degenerative IVD, and 160 proteins following IL-1β stimulus. Stimulation of MSCs with IVD conditioned media induced a more complex MSC secretome, involving more biological processes, compared to stimulation with IL-1β. The MSC response to stimulation with IVD conditioned medium was dependent on their pathological status. Conclusions The MSC secretome seemed to match the primary need of the IVD: homeostasis maintenance in the case of healthy IVDs, versus immunomodulation, adjustment of ECM synthesis and degradation disbalance, and ECM (re) organization in the case of traumatic and degenerative IVDs. These findings highlight the importance of cell preconditioning in the development of tailored secretome therapies. Graphical abstract The secretome of human bone marrow-derived mesenchymal stromal cells (MSCs) stimulated with intervertebral disc (IVD) conditioned medium was analyzed by proteomic profiling. Depending on the pathological state of the IVD, the MSC secretome protein composition indicated immunomodulatory or anabolic activity of the secretome. These findings may have implications for tailored secretome therapy for the IVD and other tissues.https://doi.org/10.1186/s13287-020-02062-2Mesenchymal stromal cellsSecretomeIntervertebral discConditioned mediumIntervertebral disc degeneration |
| spellingShingle | Sebastian Wangler Amir Kamali Christina Wapp Karin Wuertz-Kozak Sonja Häckel Claudia Fortes Lorin M. Benneker Lisbet Haglund R. Geoff Richards Mauro Alini Marianna Peroglio Sibylle Grad Uncovering the secretome of mesenchymal stromal cells exposed to healthy, traumatic, and degenerative intervertebral discs: a proteomic analysis Stem Cell Research & Therapy Mesenchymal stromal cells Secretome Intervertebral disc Conditioned medium Intervertebral disc degeneration |
| title | Uncovering the secretome of mesenchymal stromal cells exposed to healthy, traumatic, and degenerative intervertebral discs: a proteomic analysis |
| title_full | Uncovering the secretome of mesenchymal stromal cells exposed to healthy, traumatic, and degenerative intervertebral discs: a proteomic analysis |
| title_fullStr | Uncovering the secretome of mesenchymal stromal cells exposed to healthy, traumatic, and degenerative intervertebral discs: a proteomic analysis |
| title_full_unstemmed | Uncovering the secretome of mesenchymal stromal cells exposed to healthy, traumatic, and degenerative intervertebral discs: a proteomic analysis |
| title_short | Uncovering the secretome of mesenchymal stromal cells exposed to healthy, traumatic, and degenerative intervertebral discs: a proteomic analysis |
| title_sort | uncovering the secretome of mesenchymal stromal cells exposed to healthy traumatic and degenerative intervertebral discs a proteomic analysis |
| topic | Mesenchymal stromal cells Secretome Intervertebral disc Conditioned medium Intervertebral disc degeneration |
| url | https://doi.org/10.1186/s13287-020-02062-2 |
| work_keys_str_mv | AT sebastianwangler uncoveringthesecretomeofmesenchymalstromalcellsexposedtohealthytraumaticanddegenerativeintervertebraldiscsaproteomicanalysis AT amirkamali uncoveringthesecretomeofmesenchymalstromalcellsexposedtohealthytraumaticanddegenerativeintervertebraldiscsaproteomicanalysis AT christinawapp uncoveringthesecretomeofmesenchymalstromalcellsexposedtohealthytraumaticanddegenerativeintervertebraldiscsaproteomicanalysis AT karinwuertzkozak uncoveringthesecretomeofmesenchymalstromalcellsexposedtohealthytraumaticanddegenerativeintervertebraldiscsaproteomicanalysis AT sonjahackel uncoveringthesecretomeofmesenchymalstromalcellsexposedtohealthytraumaticanddegenerativeintervertebraldiscsaproteomicanalysis AT claudiafortes uncoveringthesecretomeofmesenchymalstromalcellsexposedtohealthytraumaticanddegenerativeintervertebraldiscsaproteomicanalysis AT lorinmbenneker uncoveringthesecretomeofmesenchymalstromalcellsexposedtohealthytraumaticanddegenerativeintervertebraldiscsaproteomicanalysis AT lisbethaglund uncoveringthesecretomeofmesenchymalstromalcellsexposedtohealthytraumaticanddegenerativeintervertebraldiscsaproteomicanalysis AT rgeoffrichards uncoveringthesecretomeofmesenchymalstromalcellsexposedtohealthytraumaticanddegenerativeintervertebraldiscsaproteomicanalysis AT mauroalini uncoveringthesecretomeofmesenchymalstromalcellsexposedtohealthytraumaticanddegenerativeintervertebraldiscsaproteomicanalysis AT mariannaperoglio uncoveringthesecretomeofmesenchymalstromalcellsexposedtohealthytraumaticanddegenerativeintervertebraldiscsaproteomicanalysis AT sibyllegrad uncoveringthesecretomeofmesenchymalstromalcellsexposedtohealthytraumaticanddegenerativeintervertebraldiscsaproteomicanalysis |