Osteoclast-Mediated Cell Therapy as an Attempt to Treat Elastin Specific Vascular Calcification
Inflammation and stiffness in the arteries is referred to as vascular calcification. This process is a prevalent yet poorly understood consequence of cardiovascular disease and diabetes mellitus, comorbidities with few treatments clinically available. Because this is an active process similar to bon...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/12/3643 |
| _version_ | 1797530102245883904 |
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| author | Chartrisa LaShan Simpson Jenna A. Mosier Narendra R. Vyavahare |
| author_facet | Chartrisa LaShan Simpson Jenna A. Mosier Narendra R. Vyavahare |
| author_sort | Chartrisa LaShan Simpson |
| collection | DOAJ |
| description | Inflammation and stiffness in the arteries is referred to as vascular calcification. This process is a prevalent yet poorly understood consequence of cardiovascular disease and diabetes mellitus, comorbidities with few treatments clinically available. Because this is an active process similar to bone formation, it is hypothesized that osteoclasts (OCs), bone-resorbing cells in the body, could potentially work to reverse existing calcification by resorbing bone material. The receptor activator of nuclear kappa B-ligand (RANKL) is a molecule responsible for triggering a response in monocytes and macrophages that allows them to differentiate into functional OCs. In this study, OC and RANKL delivery were employed to determine whether calcification could be attenuated. OCs were either delivered via direct injection, collagen/alginate microbeads, or collagen gel application, while RANKL was delivered via injection, through either a porcine subdermal model or aortic injury model. While in vitro results yielded a decrease in calcification using OC therapy, in vivo delivery mechanisms did not provide control or regulation to keep cells localized long enough to induce calcification reduction. However, these results do provide context and direction for the future of OC therapy, revealing necessary steps for this treatment to effectively reduce calcification in vivo. The discrepancy between in vivo and in vitro success for OC therapy points to the need for a more stable and time-controlled delivery mechanism that will allow OCs not only to remain at the site of calcification, but also to be regulated so that they are healthy and functioning normally when introduced to diseased tissue. |
| first_indexed | 2024-03-10T10:24:10Z |
| format | Article |
| id | doaj.art-2bd230b3567f418284901fc4445539f5 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T10:24:10Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-2bd230b3567f418284901fc4445539f52023-11-22T00:09:16ZengMDPI AGMolecules1420-30492021-06-012612364310.3390/molecules26123643Osteoclast-Mediated Cell Therapy as an Attempt to Treat Elastin Specific Vascular CalcificationChartrisa LaShan Simpson0Jenna A. Mosier1Narendra R. Vyavahare2Department of Biological Engineering, Mississippi State University, 130 Creelman Street, Mississippi State, MS 39762, USADepartment of Biological Engineering, Mississippi State University, 130 Creelman Street, Mississippi State, MS 39762, USADepartment of Bioengineering, 301 Rhodes Research Center, Clemson University, Clemson, SC 29634-0905, USAInflammation and stiffness in the arteries is referred to as vascular calcification. This process is a prevalent yet poorly understood consequence of cardiovascular disease and diabetes mellitus, comorbidities with few treatments clinically available. Because this is an active process similar to bone formation, it is hypothesized that osteoclasts (OCs), bone-resorbing cells in the body, could potentially work to reverse existing calcification by resorbing bone material. The receptor activator of nuclear kappa B-ligand (RANKL) is a molecule responsible for triggering a response in monocytes and macrophages that allows them to differentiate into functional OCs. In this study, OC and RANKL delivery were employed to determine whether calcification could be attenuated. OCs were either delivered via direct injection, collagen/alginate microbeads, or collagen gel application, while RANKL was delivered via injection, through either a porcine subdermal model or aortic injury model. While in vitro results yielded a decrease in calcification using OC therapy, in vivo delivery mechanisms did not provide control or regulation to keep cells localized long enough to induce calcification reduction. However, these results do provide context and direction for the future of OC therapy, revealing necessary steps for this treatment to effectively reduce calcification in vivo. The discrepancy between in vivo and in vitro success for OC therapy points to the need for a more stable and time-controlled delivery mechanism that will allow OCs not only to remain at the site of calcification, but also to be regulated so that they are healthy and functioning normally when introduced to diseased tissue.https://www.mdpi.com/1420-3049/26/12/3643cell therapydiabetes mellutiselastinmicrobeadosteoclastRANK |
| spellingShingle | Chartrisa LaShan Simpson Jenna A. Mosier Narendra R. Vyavahare Osteoclast-Mediated Cell Therapy as an Attempt to Treat Elastin Specific Vascular Calcification Molecules cell therapy diabetes mellutis elastin microbead osteoclast RANK |
| title | Osteoclast-Mediated Cell Therapy as an Attempt to Treat Elastin Specific Vascular Calcification |
| title_full | Osteoclast-Mediated Cell Therapy as an Attempt to Treat Elastin Specific Vascular Calcification |
| title_fullStr | Osteoclast-Mediated Cell Therapy as an Attempt to Treat Elastin Specific Vascular Calcification |
| title_full_unstemmed | Osteoclast-Mediated Cell Therapy as an Attempt to Treat Elastin Specific Vascular Calcification |
| title_short | Osteoclast-Mediated Cell Therapy as an Attempt to Treat Elastin Specific Vascular Calcification |
| title_sort | osteoclast mediated cell therapy as an attempt to treat elastin specific vascular calcification |
| topic | cell therapy diabetes mellutis elastin microbead osteoclast RANK |
| url | https://www.mdpi.com/1420-3049/26/12/3643 |
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