Dose-Response Tendon-Specific Markers Induction by Growth Differentiation Factor-5 in Human Bone Marrow and Umbilical Cord Mesenchymal Stem Cells
Mesenchymal stem cells derived from human bone marrow (hBM-MSCs) are utilized in tendon tissue-engineering protocols while extra-embryonic cord-derived, including from Wharton’s Jelly (hWJ-MSCs), are emerging as useful alternatives. To explore the tenogenic responsiveness of hBM-MSCs and hWJ-MSCs to...
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2020-08-01
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| Series: | International Journal of Molecular Sciences |
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| author | Maria Camilla Ciardulli Luigi Marino Erwin Pavel Lamparelli Maurizio Guida Nicholas Robert Forsyth Carmine Selleri Giovanna Della Porta Nicola Maffulli |
| author_facet | Maria Camilla Ciardulli Luigi Marino Erwin Pavel Lamparelli Maurizio Guida Nicholas Robert Forsyth Carmine Selleri Giovanna Della Porta Nicola Maffulli |
| author_sort | Maria Camilla Ciardulli |
| collection | DOAJ |
| description | Mesenchymal stem cells derived from human bone marrow (hBM-MSCs) are utilized in tendon tissue-engineering protocols while extra-embryonic cord-derived, including from Wharton’s Jelly (hWJ-MSCs), are emerging as useful alternatives. To explore the tenogenic responsiveness of hBM-MSCs and hWJ-MSCs to human Growth Differentiation Factor 5 (hGDF-5) we supplemented each at doses of 1, 10, and 100 ng/mL of hGDF-5 and determined proliferation, morphology and time-dependent expression of tenogenic markers. We evaluated the expression of collagen types 1 (COL1A1) and 3 (COL3A1), Decorin (DCN), Scleraxis-A (SCX-A), Tenascin-C (TNC) and Tenomodulin (TNMD) noting the earliest and largest increase with 100 ng/mL. With 100 ng/mL, hBM-MSCs showed up-regulation of SCX-A (1.7-fold) at Day 1, TNC (1.3-fold) and TNMD (12-fold) at Day 8. hWJ-MSCs, at the same dose, showed up-regulation of COL1A1 (3-fold), DCN (2.7-fold), SCX-A (3.8-fold) and TNC (2.3-fold) after three days of culture. hWJ-MSCs also showed larger proliferation rate and marked aggregation into a tubular-shaped system at Day 7 (with 100 ng/mL of hGDF-5). Simultaneous to this, we explored the expression of pro-inflammatory (IL-6, TNF, IL-12A, IL-1β) and anti-inflammatory (IL-10, TGF-β1) cytokines across for both cell types. hBM-MSCs exhibited a better balance of pro-inflammatory and anti-inflammatory cytokines up-regulating IL-1β (11-fold) and IL-10 (10-fold) at Day 8; hWJ-MSCs, had a slight expression of IL-12A (1.5-fold), but a greater up-regulation of IL-10 (2.5-fold). Type 1 collagen and tenomodulin proteins, detected by immunofluorescence, confirming the greater protein expression when 100 ng/mL were supplemented. In the same conditions, both cell types showed specific alignment and shape modification with a length/width ratio increase, suggesting their response in activating tenogenic commitment events, and they both potential use in 3D in vitro tissue-engineering protocols. |
| first_indexed | 2024-03-10T17:18:03Z |
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| last_indexed | 2024-03-10T17:18:03Z |
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| spelling | doaj.art-2841a3ec364f468c861f760b5f11e1b12023-11-20T10:24:56ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012116590510.3390/ijms21165905Dose-Response Tendon-Specific Markers Induction by Growth Differentiation Factor-5 in Human Bone Marrow and Umbilical Cord Mesenchymal Stem CellsMaria Camilla Ciardulli0Luigi Marino1Erwin Pavel Lamparelli2Maurizio Guida3Nicholas Robert Forsyth4Carmine Selleri5Giovanna Della Porta6Nicola Maffulli7Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Via S. Allende, 1, 84084 Baronissi (SA), ItalyDepartment of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Via S. Allende, 1, 84084 Baronissi (SA), ItalyDepartment of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Via S. Allende, 1, 84084 Baronissi (SA), ItalyDepartment of Neuroscience and Reproductive Science and Dentistry, University of Naples “Federico II”, Via Pansini, 5, 80131 Naples, ItalyGuy Hilton Research Centre, School of Pharmacy and Bioengineering, Keele University, Stoke-on-Trent ST4 7QB, UKDepartment of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Via S. Allende, 1, 84084 Baronissi (SA), ItalyDepartment of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Via S. Allende, 1, 84084 Baronissi (SA), ItalyDepartment of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Via S. Allende, 1, 84084 Baronissi (SA), ItalyMesenchymal stem cells derived from human bone marrow (hBM-MSCs) are utilized in tendon tissue-engineering protocols while extra-embryonic cord-derived, including from Wharton’s Jelly (hWJ-MSCs), are emerging as useful alternatives. To explore the tenogenic responsiveness of hBM-MSCs and hWJ-MSCs to human Growth Differentiation Factor 5 (hGDF-5) we supplemented each at doses of 1, 10, and 100 ng/mL of hGDF-5 and determined proliferation, morphology and time-dependent expression of tenogenic markers. We evaluated the expression of collagen types 1 (COL1A1) and 3 (COL3A1), Decorin (DCN), Scleraxis-A (SCX-A), Tenascin-C (TNC) and Tenomodulin (TNMD) noting the earliest and largest increase with 100 ng/mL. With 100 ng/mL, hBM-MSCs showed up-regulation of SCX-A (1.7-fold) at Day 1, TNC (1.3-fold) and TNMD (12-fold) at Day 8. hWJ-MSCs, at the same dose, showed up-regulation of COL1A1 (3-fold), DCN (2.7-fold), SCX-A (3.8-fold) and TNC (2.3-fold) after three days of culture. hWJ-MSCs also showed larger proliferation rate and marked aggregation into a tubular-shaped system at Day 7 (with 100 ng/mL of hGDF-5). Simultaneous to this, we explored the expression of pro-inflammatory (IL-6, TNF, IL-12A, IL-1β) and anti-inflammatory (IL-10, TGF-β1) cytokines across for both cell types. hBM-MSCs exhibited a better balance of pro-inflammatory and anti-inflammatory cytokines up-regulating IL-1β (11-fold) and IL-10 (10-fold) at Day 8; hWJ-MSCs, had a slight expression of IL-12A (1.5-fold), but a greater up-regulation of IL-10 (2.5-fold). Type 1 collagen and tenomodulin proteins, detected by immunofluorescence, confirming the greater protein expression when 100 ng/mL were supplemented. In the same conditions, both cell types showed specific alignment and shape modification with a length/width ratio increase, suggesting their response in activating tenogenic commitment events, and they both potential use in 3D in vitro tissue-engineering protocols.https://www.mdpi.com/1422-0067/21/16/5905Wharton’s Jelly human umbilical cord mesenchymal stem cells (hWJ-MSCs)Growth Differentiation Factor-5human bone marrow Mesenchymal Stem Cells (hBM-MSCs)tenogenic commitmentgene expressionimmunofluorescence assay |
| spellingShingle | Maria Camilla Ciardulli Luigi Marino Erwin Pavel Lamparelli Maurizio Guida Nicholas Robert Forsyth Carmine Selleri Giovanna Della Porta Nicola Maffulli Dose-Response Tendon-Specific Markers Induction by Growth Differentiation Factor-5 in Human Bone Marrow and Umbilical Cord Mesenchymal Stem Cells International Journal of Molecular Sciences Wharton’s Jelly human umbilical cord mesenchymal stem cells (hWJ-MSCs) Growth Differentiation Factor-5 human bone marrow Mesenchymal Stem Cells (hBM-MSCs) tenogenic commitment gene expression immunofluorescence assay |
| title | Dose-Response Tendon-Specific Markers Induction by Growth Differentiation Factor-5 in Human Bone Marrow and Umbilical Cord Mesenchymal Stem Cells |
| title_full | Dose-Response Tendon-Specific Markers Induction by Growth Differentiation Factor-5 in Human Bone Marrow and Umbilical Cord Mesenchymal Stem Cells |
| title_fullStr | Dose-Response Tendon-Specific Markers Induction by Growth Differentiation Factor-5 in Human Bone Marrow and Umbilical Cord Mesenchymal Stem Cells |
| title_full_unstemmed | Dose-Response Tendon-Specific Markers Induction by Growth Differentiation Factor-5 in Human Bone Marrow and Umbilical Cord Mesenchymal Stem Cells |
| title_short | Dose-Response Tendon-Specific Markers Induction by Growth Differentiation Factor-5 in Human Bone Marrow and Umbilical Cord Mesenchymal Stem Cells |
| title_sort | dose response tendon specific markers induction by growth differentiation factor 5 in human bone marrow and umbilical cord mesenchymal stem cells |
| topic | Wharton’s Jelly human umbilical cord mesenchymal stem cells (hWJ-MSCs) Growth Differentiation Factor-5 human bone marrow Mesenchymal Stem Cells (hBM-MSCs) tenogenic commitment gene expression immunofluorescence assay |
| url | https://www.mdpi.com/1422-0067/21/16/5905 |
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