Long-Term Contribution of Human Bone Marrow Mesenchymal Stromal Cells to Skeletal Muscle Regeneration in Mice
Mesenchymal stromal cells (MSCs) are attractive for cellular therapy of muscular dystrophies as they are easy to procure, can be greatly expanded ex vivo, and contribute to skeletal muscle repair in vivo. However, detailed information about the contribution of bone marrow (BM)-derived human MSCs (BM...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2011-03-01
|
| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368910X522117 |
| _version_ | 1819033783990484992 |
|---|---|
| author | Anabel S. De La Garza-Rodea Ietje Van Der Velde Hester Boersma Manuel A. F. V. Gonçalves Dirk W. Van Bekkum Antoine A. F. De Vries Shoshan Knaän-Shanzer Ph.D. |
| author_facet | Anabel S. De La Garza-Rodea Ietje Van Der Velde Hester Boersma Manuel A. F. V. Gonçalves Dirk W. Van Bekkum Antoine A. F. De Vries Shoshan Knaän-Shanzer Ph.D. |
| author_sort | Anabel S. De La Garza-Rodea |
| collection | DOAJ |
| description | Mesenchymal stromal cells (MSCs) are attractive for cellular therapy of muscular dystrophies as they are easy to procure, can be greatly expanded ex vivo, and contribute to skeletal muscle repair in vivo. However, detailed information about the contribution of bone marrow (BM)-derived human MSCs (BM-hMSCs) to skeletal muscle regeneration in vivo is very limited. Here, we present the results of a comprehensive study of the fate of LacZ -tagged BM-hMSCs following implantation in cardiotoxin (CTX)-injured tibialis anterior muscles (TAMs) of immunodeficient mice. β-Galactosidase-positive (β-gal + ) human-mouse hybrid myofibers (HMs) were counted in serial cross sections over the full length of the treated TAMs of groups of mice at monthly intervals. The number of human cells was estimated using chemiluminescence assays. While the number of human cells declined gradually to about 10% of the injected cells at 60 days after transplantation, the number of HMs increased from day 10 onwards, reaching 104 ± 39.1 per TAM at 4 months postinjection. β-gal + cells and HMs were distributed over the entire muscle, indicating migration of the former from the central injection site to the ends of the TAMs. The identification of HMs that stained positive for human spectrin suggests myogenic reprogramming of hMSC nuclei. In summary, our findings reveal that BM-hMSCs continue to participate in the regeneration/remodeling of CTX-injured TAMs, resulting in ±5% HMs at 4 months after damage induction. Moreover, donor-derived cells were shown to express genetic information, both endogenous and transgenic, in recipient myofibers. |
| first_indexed | 2024-12-21T07:23:20Z |
| format | Article |
| id | doaj.art-032f4e397aa242b5aa0ed6bba3c24b9c |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-21T07:23:20Z |
| publishDate | 2011-03-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-032f4e397aa242b5aa0ed6bba3c24b9c2022-12-21T19:11:44ZengSAGE PublishingCell Transplantation0963-68971555-38922011-03-012010.3727/096368910X522117Long-Term Contribution of Human Bone Marrow Mesenchymal Stromal Cells to Skeletal Muscle Regeneration in MiceAnabel S. De La Garza-Rodea0Ietje Van Der Velde1Hester Boersma2Manuel A. F. V. Gonçalves3Dirk W. Van Bekkum4Antoine A. F. De Vries5Shoshan Knaän-Shanzer Ph.D.6Virus and Stem Cell Biology Laboratory, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the NetherlandsVirus and Stem Cell Biology Laboratory, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the NetherlandsVirus and Stem Cell Biology Laboratory, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the NetherlandsVirus and Stem Cell Biology Laboratory, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the NetherlandsVirus and Stem Cell Biology Laboratory, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the NetherlandsVirus and Stem Cell Biology Laboratory, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the NetherlandsVirus and Stem Cell Biology Laboratory, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the NetherlandsMesenchymal stromal cells (MSCs) are attractive for cellular therapy of muscular dystrophies as they are easy to procure, can be greatly expanded ex vivo, and contribute to skeletal muscle repair in vivo. However, detailed information about the contribution of bone marrow (BM)-derived human MSCs (BM-hMSCs) to skeletal muscle regeneration in vivo is very limited. Here, we present the results of a comprehensive study of the fate of LacZ -tagged BM-hMSCs following implantation in cardiotoxin (CTX)-injured tibialis anterior muscles (TAMs) of immunodeficient mice. β-Galactosidase-positive (β-gal + ) human-mouse hybrid myofibers (HMs) were counted in serial cross sections over the full length of the treated TAMs of groups of mice at monthly intervals. The number of human cells was estimated using chemiluminescence assays. While the number of human cells declined gradually to about 10% of the injected cells at 60 days after transplantation, the number of HMs increased from day 10 onwards, reaching 104 ± 39.1 per TAM at 4 months postinjection. β-gal + cells and HMs were distributed over the entire muscle, indicating migration of the former from the central injection site to the ends of the TAMs. The identification of HMs that stained positive for human spectrin suggests myogenic reprogramming of hMSC nuclei. In summary, our findings reveal that BM-hMSCs continue to participate in the regeneration/remodeling of CTX-injured TAMs, resulting in ±5% HMs at 4 months after damage induction. Moreover, donor-derived cells were shown to express genetic information, both endogenous and transgenic, in recipient myofibers.https://doi.org/10.3727/096368910X522117 |
| spellingShingle | Anabel S. De La Garza-Rodea Ietje Van Der Velde Hester Boersma Manuel A. F. V. Gonçalves Dirk W. Van Bekkum Antoine A. F. De Vries Shoshan Knaän-Shanzer Ph.D. Long-Term Contribution of Human Bone Marrow Mesenchymal Stromal Cells to Skeletal Muscle Regeneration in Mice Cell Transplantation |
| title | Long-Term Contribution of Human Bone Marrow Mesenchymal Stromal Cells to Skeletal Muscle Regeneration in Mice |
| title_full | Long-Term Contribution of Human Bone Marrow Mesenchymal Stromal Cells to Skeletal Muscle Regeneration in Mice |
| title_fullStr | Long-Term Contribution of Human Bone Marrow Mesenchymal Stromal Cells to Skeletal Muscle Regeneration in Mice |
| title_full_unstemmed | Long-Term Contribution of Human Bone Marrow Mesenchymal Stromal Cells to Skeletal Muscle Regeneration in Mice |
| title_short | Long-Term Contribution of Human Bone Marrow Mesenchymal Stromal Cells to Skeletal Muscle Regeneration in Mice |
| title_sort | long term contribution of human bone marrow mesenchymal stromal cells to skeletal muscle regeneration in mice |
| url | https://doi.org/10.3727/096368910X522117 |
| work_keys_str_mv | AT anabelsdelagarzarodea longtermcontributionofhumanbonemarrowmesenchymalstromalcellstoskeletalmuscleregenerationinmice AT ietjevandervelde longtermcontributionofhumanbonemarrowmesenchymalstromalcellstoskeletalmuscleregenerationinmice AT hesterboersma longtermcontributionofhumanbonemarrowmesenchymalstromalcellstoskeletalmuscleregenerationinmice AT manuelafvgoncalves longtermcontributionofhumanbonemarrowmesenchymalstromalcellstoskeletalmuscleregenerationinmice AT dirkwvanbekkum longtermcontributionofhumanbonemarrowmesenchymalstromalcellstoskeletalmuscleregenerationinmice AT antoineafdevries longtermcontributionofhumanbonemarrowmesenchymalstromalcellstoskeletalmuscleregenerationinmice AT shoshanknaanshanzerphd longtermcontributionofhumanbonemarrowmesenchymalstromalcellstoskeletalmuscleregenerationinmice |