Cellular activation patterns of CD10+ fibro-adipogenic progenitors across acquired disease states in human skeletal muscle biopsies
Background: Fibro-adipogenic progenitors (FAP) are muscle resident mesenchymal stem cells pivotal for regulation of myofiber repair. Experimental results show in addition involvement in a range of other pathological conditions and potential for pharmacological intervention. FAP histopathology in hu...
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| Format: | Article |
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University of Münster / Open Journals System
2024-02-01
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| Series: | Free Neuropathology |
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| Online Access: | https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/5162 |
| _version_ | 1797317501637361664 |
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| author | Peter Schutz Simon Cheung Lin Yi Fabio M. V. Rossi |
| author_facet | Peter Schutz Simon Cheung Lin Yi Fabio M. V. Rossi |
| author_sort | Peter Schutz |
| collection | DOAJ |
| description |
Background: Fibro-adipogenic progenitors (FAP) are muscle resident mesenchymal stem cells pivotal for regulation of myofiber repair. Experimental results show in addition involvement in a range of other pathological conditions and potential for pharmacological intervention. FAP histopathology in human muscle biopsies is largely unknown, but has potential to inform translational research.
Methods: CD10+ FAPs in 32 archival muscle biopsies from 8 groups (normal, dermatomyositis, inclusion body myositis (IBM), anti-synthetase syndrome, immune-mediated necrotizing myopathy (IMNM), denervation, type 2 atrophy, rhabdomyolysis) were visualized by CD10 immunohistochemistry and their histology compared. Groups are compared by semi-quantitative scoring.
Results: Histological activation of endomysial CD10+ FAPs includes prominent expansion of a network of cell processes surrounding muscle fibers, as well as endomysial cell clusters evidencing proliferation. Prominence of periarteriolar processes is a notable feature in some pathologies. FAP activation is often associated with fiber degeneration/regeneration, foci of inflammation, and denervation in keeping with experimental results. Type 2 atrophy shows no evidence of FAP activation. Dermatomyositis and anti-synthetase syndrome associated myositis demonstrate diffuse activation.
Conclusion: Assessment of CD10+ FAP activation is routinely possible using CD10 immunohistochemistry and demonstrates several patterns in keeping with preclinical results. Prominent expansion of FAP processes surrounding myofibers suggests enhanced interaction between myofiber/basement membranes and FAPs during activation. The presence of diffuse FAP activation in dermatomyositis biopsies unrelated to fiber repair raises the possibility of FAP activation as part of the autoimmune process. Future diagnostic applications, clinical significance and therapeutic potential remain to be elucidated.
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| first_indexed | 2024-03-08T03:35:57Z |
| format | Article |
| id | doaj.art-23e05294fe7448bfaa0ca2d998b59020 |
| institution | Directory Open Access Journal |
| issn | 2699-4445 |
| language | English |
| last_indexed | 2024-03-08T03:35:57Z |
| publishDate | 2024-02-01 |
| publisher | University of Münster / Open Journals System |
| record_format | Article |
| series | Free Neuropathology |
| spelling | doaj.art-23e05294fe7448bfaa0ca2d998b590202024-02-10T03:08:16ZengUniversity of Münster / Open Journals SystemFree Neuropathology2699-44452024-02-01510.17879/freeneuropathology-2024-5162Cellular activation patterns of CD10+ fibro-adipogenic progenitors across acquired disease states in human skeletal muscle biopsiesPeter Schutz0Simon Cheung1Lin Yi2Fabio M. V. Rossi3Department of Pathology, University of British Columbia, Vancouver, CanadaDepartment of Pathology, Vancouver General Hospital, Vancouver, CanadaSchool of Biomedical Engineering, University of British Columbia, Vancouver, CanadaSchool of Biomedical Engineering, University of British Columbia, Vancouver, Canada Background: Fibro-adipogenic progenitors (FAP) are muscle resident mesenchymal stem cells pivotal for regulation of myofiber repair. Experimental results show in addition involvement in a range of other pathological conditions and potential for pharmacological intervention. FAP histopathology in human muscle biopsies is largely unknown, but has potential to inform translational research. Methods: CD10+ FAPs in 32 archival muscle biopsies from 8 groups (normal, dermatomyositis, inclusion body myositis (IBM), anti-synthetase syndrome, immune-mediated necrotizing myopathy (IMNM), denervation, type 2 atrophy, rhabdomyolysis) were visualized by CD10 immunohistochemistry and their histology compared. Groups are compared by semi-quantitative scoring. Results: Histological activation of endomysial CD10+ FAPs includes prominent expansion of a network of cell processes surrounding muscle fibers, as well as endomysial cell clusters evidencing proliferation. Prominence of periarteriolar processes is a notable feature in some pathologies. FAP activation is often associated with fiber degeneration/regeneration, foci of inflammation, and denervation in keeping with experimental results. Type 2 atrophy shows no evidence of FAP activation. Dermatomyositis and anti-synthetase syndrome associated myositis demonstrate diffuse activation. Conclusion: Assessment of CD10+ FAP activation is routinely possible using CD10 immunohistochemistry and demonstrates several patterns in keeping with preclinical results. Prominent expansion of FAP processes surrounding myofibers suggests enhanced interaction between myofiber/basement membranes and FAPs during activation. The presence of diffuse FAP activation in dermatomyositis biopsies unrelated to fiber repair raises the possibility of FAP activation as part of the autoimmune process. Future diagnostic applications, clinical significance and therapeutic potential remain to be elucidated. https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/5162Fibro-adipogenic progenitorInflammatory myopathyDenervationCD10Skeletal musclePeriarteriolar |
| spellingShingle | Peter Schutz Simon Cheung Lin Yi Fabio M. V. Rossi Cellular activation patterns of CD10+ fibro-adipogenic progenitors across acquired disease states in human skeletal muscle biopsies Free Neuropathology Fibro-adipogenic progenitor Inflammatory myopathy Denervation CD10 Skeletal muscle Periarteriolar |
| title | Cellular activation patterns of CD10+ fibro-adipogenic progenitors across acquired disease states in human skeletal muscle biopsies |
| title_full | Cellular activation patterns of CD10+ fibro-adipogenic progenitors across acquired disease states in human skeletal muscle biopsies |
| title_fullStr | Cellular activation patterns of CD10+ fibro-adipogenic progenitors across acquired disease states in human skeletal muscle biopsies |
| title_full_unstemmed | Cellular activation patterns of CD10+ fibro-adipogenic progenitors across acquired disease states in human skeletal muscle biopsies |
| title_short | Cellular activation patterns of CD10+ fibro-adipogenic progenitors across acquired disease states in human skeletal muscle biopsies |
| title_sort | cellular activation patterns of cd10 fibro adipogenic progenitors across acquired disease states in human skeletal muscle biopsies |
| topic | Fibro-adipogenic progenitor Inflammatory myopathy Denervation CD10 Skeletal muscle Periarteriolar |
| url | https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/5162 |
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