Skeletal Muscle Resident Progenitor Cells Coexpress Mesenchymal and Myogenic Markers and Are Not Affected by Chronic Heart Failure-Induced Dysregulations
Background and Purpose. In heart failure (HF), metabolic alterations induce skeletal muscle wasting and decrease of exercise capacity and quality of life. The activation of skeletal muscle regeneration potential is a prospective strategy to reduce muscle wasting; therefore, the aim of this project w...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-01-01
|
| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2019/5690345 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849686569641836544 |
|---|---|
| author | R. I. Dmitrieva T. A. Lelyavina M. Y. Komarova V. L. Galenko O. A. Ivanova P. A. Tikanova N. V. Khromova A. S. Golovkin M. A. Bortsova A. Sergushichev M. Yu. Sitnikova A. A. Kostareva |
| author_facet | R. I. Dmitrieva T. A. Lelyavina M. Y. Komarova V. L. Galenko O. A. Ivanova P. A. Tikanova N. V. Khromova A. S. Golovkin M. A. Bortsova A. Sergushichev M. Yu. Sitnikova A. A. Kostareva |
| author_sort | R. I. Dmitrieva |
| collection | DOAJ |
| description | Background and Purpose. In heart failure (HF), metabolic alterations induce skeletal muscle wasting and decrease of exercise capacity and quality of life. The activation of skeletal muscle regeneration potential is a prospective strategy to reduce muscle wasting; therefore, the aim of this project was to determine if functional properties of skeletal muscle mesenchymal progenitor cells (SM-MPC) were affected by HF-induced functional and metabolic dysregulations. Methods. Gastrocnemius muscle biopsy samples were obtained from 3 healthy donors (HD) and 12 HF patients to purify mRNA for further analysis and to isolate SM-MPC. Cells were expanded in vitro and characterized by immunocytochemistry and flow cytometry for expression of mesenchymal (CD105/CD73/CD166/CD146/CD140b/CD140a/VIM) and myogenic (Myf5/CD56/MyoG) markers. Cells were induced to differentiate and were then analyzed by immunostaining and Q-PCR to verify the efficiency of differentiation. The expression of genes that control muscle metabolism and development was compared for HD/HF patients in both muscle biopsy and in vitro-differentiated myotubes. Results. The upregulation of MYH3/MYH8/Myf6 detected in HF skeletal muscle along with metabolic alterations indicates chronic pathological activation of the muscle developmental program. SM-MPC isolated from HD and HF patients represented a mixed population that coexpresses both mesenchymal and myogenic markers and differs from AD-MMSC, BM-MMSC, and IMF-MSC. The functional properties of SM-MPC did not differ between HD and HF patients. Conclusion. In the present work, we demonstrate that the metabolic and functional alterations we detected in skeletal muscle from HF patients do not dramatically affect the functional properties of purified and expanded in vitro SM-MPC. We speculate that skeletal muscle progenitor cells are protected by their niche and under beneficial circumstances could contribute to muscle restoration and prevention and treatment of muscle wasting. The potential new therapeutic strategies of HF-induced skeletal muscle wasting should be targeted on both activation of SM-MPC regeneration potential and improvement of skeletal muscle metabolic status to provide a favorable environment for SM-MPC-driven muscle restoration. |
| format | Article |
| id | doaj-art-bf850b3bc79e4ec0ab84d133e1ff312b |
| institution | DOAJ |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-bf850b3bc79e4ec0ab84d133e1ff312b2025-08-20T03:22:39ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/56903455690345Skeletal Muscle Resident Progenitor Cells Coexpress Mesenchymal and Myogenic Markers and Are Not Affected by Chronic Heart Failure-Induced DysregulationsR. I. Dmitrieva0T. A. Lelyavina1M. Y. Komarova2V. L. Galenko3O. A. Ivanova4P. A. Tikanova5N. V. Khromova6A. S. Golovkin7M. A. Bortsova8A. Sergushichev9M. Yu. Sitnikova10A. A. Kostareva11Institute of Molecular Biology and Genetics, National Almazov Medical Research Centre, Saint Petersburg, RussiaHeart Failure Department, National Almazov Medical Research Centre, Saint Petersburg, RussiaPeter the Great St. Petersburg Polytechnic University, Saint Petersburg, RussiaHeart Failure Department, National Almazov Medical Research Centre, Saint Petersburg, RussiaITMO University, Saint Petersburg, RussiaSaint Petersburg State University, Saint Petersburg, RussiaInstitute of Molecular Biology and Genetics, National Almazov Medical Research Centre, Saint Petersburg, RussiaInstitute of Molecular Biology and Genetics, National Almazov Medical Research Centre, Saint Petersburg, RussiaHeart Failure Department, National Almazov Medical Research Centre, Saint Petersburg, RussiaITMO University, Saint Petersburg, RussiaHeart Failure Department, National Almazov Medical Research Centre, Saint Petersburg, RussiaInstitute of Molecular Biology and Genetics, National Almazov Medical Research Centre, Saint Petersburg, RussiaBackground and Purpose. In heart failure (HF), metabolic alterations induce skeletal muscle wasting and decrease of exercise capacity and quality of life. The activation of skeletal muscle regeneration potential is a prospective strategy to reduce muscle wasting; therefore, the aim of this project was to determine if functional properties of skeletal muscle mesenchymal progenitor cells (SM-MPC) were affected by HF-induced functional and metabolic dysregulations. Methods. Gastrocnemius muscle biopsy samples were obtained from 3 healthy donors (HD) and 12 HF patients to purify mRNA for further analysis and to isolate SM-MPC. Cells were expanded in vitro and characterized by immunocytochemistry and flow cytometry for expression of mesenchymal (CD105/CD73/CD166/CD146/CD140b/CD140a/VIM) and myogenic (Myf5/CD56/MyoG) markers. Cells were induced to differentiate and were then analyzed by immunostaining and Q-PCR to verify the efficiency of differentiation. The expression of genes that control muscle metabolism and development was compared for HD/HF patients in both muscle biopsy and in vitro-differentiated myotubes. Results. The upregulation of MYH3/MYH8/Myf6 detected in HF skeletal muscle along with metabolic alterations indicates chronic pathological activation of the muscle developmental program. SM-MPC isolated from HD and HF patients represented a mixed population that coexpresses both mesenchymal and myogenic markers and differs from AD-MMSC, BM-MMSC, and IMF-MSC. The functional properties of SM-MPC did not differ between HD and HF patients. Conclusion. In the present work, we demonstrate that the metabolic and functional alterations we detected in skeletal muscle from HF patients do not dramatically affect the functional properties of purified and expanded in vitro SM-MPC. We speculate that skeletal muscle progenitor cells are protected by their niche and under beneficial circumstances could contribute to muscle restoration and prevention and treatment of muscle wasting. The potential new therapeutic strategies of HF-induced skeletal muscle wasting should be targeted on both activation of SM-MPC regeneration potential and improvement of skeletal muscle metabolic status to provide a favorable environment for SM-MPC-driven muscle restoration.http://dx.doi.org/10.1155/2019/5690345 |
| spellingShingle | R. I. Dmitrieva T. A. Lelyavina M. Y. Komarova V. L. Galenko O. A. Ivanova P. A. Tikanova N. V. Khromova A. S. Golovkin M. A. Bortsova A. Sergushichev M. Yu. Sitnikova A. A. Kostareva Skeletal Muscle Resident Progenitor Cells Coexpress Mesenchymal and Myogenic Markers and Are Not Affected by Chronic Heart Failure-Induced Dysregulations Stem Cells International |
| title | Skeletal Muscle Resident Progenitor Cells Coexpress Mesenchymal and Myogenic Markers and Are Not Affected by Chronic Heart Failure-Induced Dysregulations |
| title_full | Skeletal Muscle Resident Progenitor Cells Coexpress Mesenchymal and Myogenic Markers and Are Not Affected by Chronic Heart Failure-Induced Dysregulations |
| title_fullStr | Skeletal Muscle Resident Progenitor Cells Coexpress Mesenchymal and Myogenic Markers and Are Not Affected by Chronic Heart Failure-Induced Dysregulations |
| title_full_unstemmed | Skeletal Muscle Resident Progenitor Cells Coexpress Mesenchymal and Myogenic Markers and Are Not Affected by Chronic Heart Failure-Induced Dysregulations |
| title_short | Skeletal Muscle Resident Progenitor Cells Coexpress Mesenchymal and Myogenic Markers and Are Not Affected by Chronic Heart Failure-Induced Dysregulations |
| title_sort | skeletal muscle resident progenitor cells coexpress mesenchymal and myogenic markers and are not affected by chronic heart failure induced dysregulations |
| url | http://dx.doi.org/10.1155/2019/5690345 |
| work_keys_str_mv | AT ridmitrieva skeletalmuscleresidentprogenitorcellscoexpressmesenchymalandmyogenicmarkersandarenotaffectedbychronicheartfailureinduceddysregulations AT talelyavina skeletalmuscleresidentprogenitorcellscoexpressmesenchymalandmyogenicmarkersandarenotaffectedbychronicheartfailureinduceddysregulations AT mykomarova skeletalmuscleresidentprogenitorcellscoexpressmesenchymalandmyogenicmarkersandarenotaffectedbychronicheartfailureinduceddysregulations AT vlgalenko skeletalmuscleresidentprogenitorcellscoexpressmesenchymalandmyogenicmarkersandarenotaffectedbychronicheartfailureinduceddysregulations AT oaivanova skeletalmuscleresidentprogenitorcellscoexpressmesenchymalandmyogenicmarkersandarenotaffectedbychronicheartfailureinduceddysregulations AT patikanova skeletalmuscleresidentprogenitorcellscoexpressmesenchymalandmyogenicmarkersandarenotaffectedbychronicheartfailureinduceddysregulations AT nvkhromova skeletalmuscleresidentprogenitorcellscoexpressmesenchymalandmyogenicmarkersandarenotaffectedbychronicheartfailureinduceddysregulations AT asgolovkin skeletalmuscleresidentprogenitorcellscoexpressmesenchymalandmyogenicmarkersandarenotaffectedbychronicheartfailureinduceddysregulations AT mabortsova skeletalmuscleresidentprogenitorcellscoexpressmesenchymalandmyogenicmarkersandarenotaffectedbychronicheartfailureinduceddysregulations AT asergushichev skeletalmuscleresidentprogenitorcellscoexpressmesenchymalandmyogenicmarkersandarenotaffectedbychronicheartfailureinduceddysregulations AT myusitnikova skeletalmuscleresidentprogenitorcellscoexpressmesenchymalandmyogenicmarkersandarenotaffectedbychronicheartfailureinduceddysregulations AT aakostareva skeletalmuscleresidentprogenitorcellscoexpressmesenchymalandmyogenicmarkersandarenotaffectedbychronicheartfailureinduceddysregulations |