Mesenchymal stem cell secretome improves tendon cell viability in vitro and tendon-bone healing in vivo when a tissue engineering strategy is used in a rat model of chronic massive rotator cuff tear

Background: Massive rotator cuff tears (MRCTs) represent a major clinical concern, especially when degeneration and chronicity are involved, which highly compromise healing capacity. Purpose: To study the effect of the secretome of mesenchymal stem cells (MSCs) on tendon cells (TCs) followed by the...

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Main Authors: Sevivas, Nuno, Teixeira, Fábio Gabriel, Portugal, Raquel, Direito-Santos, Bruno, Espregueira-Mendes, João, Oliveira, Filipe J., Silva, Rui F., Sousa, Nuno, Sow, Wan Ting, Nguyen, Luong T.H., Ng, Kee Woei, Salgado, António J.
Other Authors: School of Materials Science & Engineering
Format: Journal Article
Language:English
Published: 2019
Subjects:
Online Access:https://hdl.handle.net/10356/86105
http://hdl.handle.net/10220/49260
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author Sevivas, Nuno
Teixeira, Fábio Gabriel
Portugal, Raquel
Direito-Santos, Bruno
Espregueira-Mendes, João
Oliveira, Filipe J.
Silva, Rui F.
Sousa, Nuno
Sow, Wan Ting
Nguyen, Luong T.H.
Ng, Kee Woei
Salgado, António J.
author2 School of Materials Science & Engineering
author_facet School of Materials Science & Engineering
Sevivas, Nuno
Teixeira, Fábio Gabriel
Portugal, Raquel
Direito-Santos, Bruno
Espregueira-Mendes, João
Oliveira, Filipe J.
Silva, Rui F.
Sousa, Nuno
Sow, Wan Ting
Nguyen, Luong T.H.
Ng, Kee Woei
Salgado, António J.
author_sort Sevivas, Nuno
collection NTU
description Background: Massive rotator cuff tears (MRCTs) represent a major clinical concern, especially when degeneration and chronicity are involved, which highly compromise healing capacity. Purpose: To study the effect of the secretome of mesenchymal stem cells (MSCs) on tendon cells (TCs) followed by the combination of these activated TCs with an electrospun keratin-based scaffold to develop a tissue engineering strategy to improve tendon-bone interface (TBi) healing in a chronic MRCT rat model. Study Design: Controlled laboratory study. Methods: Human TCs (hTCs) cultured with the human MSCs (hMSCs) secretome (as conditioned media [CM]) were combined with keratin electrospun scaffolds and further implanted in a chronic MRCT rat model. Wistar-Han rats (N = 15) were randomly assigned to 1 of 3 groups: untreated lesion (MRCT group, n = 5), lesion treated with a scaffold only (scaffold-only group, n = 5), and lesion treated with a scaffold seeded with hTCs preconditioned with hMSCs-CM (STC_hMSC_CM group, n = 5). After sacrifice, 16 weeks after surgery, the rotator cuff TBi was harvested for histological analysis and biomechanical testing. Results: The hMSCs secretome increased hTCs viability and density in vitro. In vivo, a significant improvement of the tendon maturing score was observed in the STC_hMSC_CM group (mean ± standard error of the mean, 15.6 ± 1.08) compared with the MRCT group (11.0 ± 1.38; P < .05). Biomechanical tests revealed a significant increase in the total elongation to rupture (STC_hMSC_CM, 11.99 ± 3.30 mm; scaffold-only, 9.89 ± 3.47 mm; MRCT, 5.86 ± 3.16 mm; P < .05) as well as a lower stiffness (STC_hMSC_CM, 6.25 ± 1.74 N/mm; scaffold-only, 6.72 ± 1.28 N/mm; MRCT, 11.54 ± 2.99 N/mm; P < .01). Conclusion:The results demonstrated that hMSCs-CM increased hTCs viability and density in vitro. Clear benefits also were observed when these primed cells were integrated into a tissue engineering strategy with an electrospun keratin scaffold, as evidenced by improved histological and biomechanical properties for the STC_hMSC_CM group compared with the MRCT group.Clinical Relevance: This work supports further investigation into the use of MSC secretome for priming TCs toward a more differentiated phenotype, and it promotes the tissue engineering strategy as a promising modality to help improve treatment outcomes for chronic MRCTs.
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spelling ntu-10356/861052020-06-01T10:13:55Z Mesenchymal stem cell secretome improves tendon cell viability in vitro and tendon-bone healing in vivo when a tissue engineering strategy is used in a rat model of chronic massive rotator cuff tear Sevivas, Nuno Teixeira, Fábio Gabriel Portugal, Raquel Direito-Santos, Bruno Espregueira-Mendes, João Oliveira, Filipe J. Silva, Rui F. Sousa, Nuno Sow, Wan Ting Nguyen, Luong T.H. Ng, Kee Woei Salgado, António J. School of Materials Science & Engineering Engineering::Materials Massive Rotator Cuff Tear hMSC Secretome Background: Massive rotator cuff tears (MRCTs) represent a major clinical concern, especially when degeneration and chronicity are involved, which highly compromise healing capacity. Purpose: To study the effect of the secretome of mesenchymal stem cells (MSCs) on tendon cells (TCs) followed by the combination of these activated TCs with an electrospun keratin-based scaffold to develop a tissue engineering strategy to improve tendon-bone interface (TBi) healing in a chronic MRCT rat model. Study Design: Controlled laboratory study. Methods: Human TCs (hTCs) cultured with the human MSCs (hMSCs) secretome (as conditioned media [CM]) were combined with keratin electrospun scaffolds and further implanted in a chronic MRCT rat model. Wistar-Han rats (N = 15) were randomly assigned to 1 of 3 groups: untreated lesion (MRCT group, n = 5), lesion treated with a scaffold only (scaffold-only group, n = 5), and lesion treated with a scaffold seeded with hTCs preconditioned with hMSCs-CM (STC_hMSC_CM group, n = 5). After sacrifice, 16 weeks after surgery, the rotator cuff TBi was harvested for histological analysis and biomechanical testing. Results: The hMSCs secretome increased hTCs viability and density in vitro. In vivo, a significant improvement of the tendon maturing score was observed in the STC_hMSC_CM group (mean ± standard error of the mean, 15.6 ± 1.08) compared with the MRCT group (11.0 ± 1.38; P < .05). Biomechanical tests revealed a significant increase in the total elongation to rupture (STC_hMSC_CM, 11.99 ± 3.30 mm; scaffold-only, 9.89 ± 3.47 mm; MRCT, 5.86 ± 3.16 mm; P < .05) as well as a lower stiffness (STC_hMSC_CM, 6.25 ± 1.74 N/mm; scaffold-only, 6.72 ± 1.28 N/mm; MRCT, 11.54 ± 2.99 N/mm; P < .01). Conclusion:The results demonstrated that hMSCs-CM increased hTCs viability and density in vitro. Clear benefits also were observed when these primed cells were integrated into a tissue engineering strategy with an electrospun keratin scaffold, as evidenced by improved histological and biomechanical properties for the STC_hMSC_CM group compared with the MRCT group.Clinical Relevance: This work supports further investigation into the use of MSC secretome for priming TCs toward a more differentiated phenotype, and it promotes the tissue engineering strategy as a promising modality to help improve treatment outcomes for chronic MRCTs. 2019-07-10T08:19:21Z 2019-12-06T16:16:09Z 2019-07-10T08:19:21Z 2019-12-06T16:16:09Z 2017 Journal Article Sevivas, N., Teixeira, F. G., Portugal, R., Direito-Santos, B., Espregueira-Mendes, J., Oliveira, F. J., . . . Salgado, A. J. (2017). Mesenchymal Stem Cell Secretome Improves Tendon Cell Viability In Vitro and Tendon-Bone Healing In Vivo When a Tissue Engineering Strategy Is Used in a Rat Model of Chronic Massive Rotator Cuff Tear. The American Journal of Sports Medicine, 46(2), 449-459. doi:10.1177/0363546517735850 0363-5465 https://hdl.handle.net/10356/86105 http://hdl.handle.net/10220/49260 10.1177/0363546517735850 en The American Journal of Sports Medicine © 2017 The Author(s). All rights reserved.
spellingShingle Engineering::Materials
Massive Rotator Cuff Tear
hMSC Secretome
Sevivas, Nuno
Teixeira, Fábio Gabriel
Portugal, Raquel
Direito-Santos, Bruno
Espregueira-Mendes, João
Oliveira, Filipe J.
Silva, Rui F.
Sousa, Nuno
Sow, Wan Ting
Nguyen, Luong T.H.
Ng, Kee Woei
Salgado, António J.
Mesenchymal stem cell secretome improves tendon cell viability in vitro and tendon-bone healing in vivo when a tissue engineering strategy is used in a rat model of chronic massive rotator cuff tear
title Mesenchymal stem cell secretome improves tendon cell viability in vitro and tendon-bone healing in vivo when a tissue engineering strategy is used in a rat model of chronic massive rotator cuff tear
title_full Mesenchymal stem cell secretome improves tendon cell viability in vitro and tendon-bone healing in vivo when a tissue engineering strategy is used in a rat model of chronic massive rotator cuff tear
title_fullStr Mesenchymal stem cell secretome improves tendon cell viability in vitro and tendon-bone healing in vivo when a tissue engineering strategy is used in a rat model of chronic massive rotator cuff tear
title_full_unstemmed Mesenchymal stem cell secretome improves tendon cell viability in vitro and tendon-bone healing in vivo when a tissue engineering strategy is used in a rat model of chronic massive rotator cuff tear
title_short Mesenchymal stem cell secretome improves tendon cell viability in vitro and tendon-bone healing in vivo when a tissue engineering strategy is used in a rat model of chronic massive rotator cuff tear
title_sort mesenchymal stem cell secretome improves tendon cell viability in vitro and tendon bone healing in vivo when a tissue engineering strategy is used in a rat model of chronic massive rotator cuff tear
topic Engineering::Materials
Massive Rotator Cuff Tear
hMSC Secretome
url https://hdl.handle.net/10356/86105
http://hdl.handle.net/10220/49260
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