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Article

Dose-Response Tendon-Specific Markers Induction by Growth Differentiation Factor-5 in Human Bone Marrow and Umbilical Cord Mesenchymal Stem Cells

1
Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Via S. Allende, 1, 84084 Baronissi (SA), Italy
2
Department of Neuroscience and Reproductive Science and Dentistry, University of Naples “Federico II”, Via Pansini, 5, 80131 Naples, Italy
3
Guy Hilton Research Centre, School of Pharmacy and Bioengineering, Keele University, Stoke-on-Trent ST4 7QB, UK
4
Mile End Hospital, Centre for Sports and Exercise Medicine, Queen Mary University of London, Barts and the London School of Medicine and Dentistry, 275 Bancroft Road, London E1 4DG, UK
*
Author to whom correspondence should be addressed.
The authors equally contributed to the work.
The authors shared the co-last authorship.
Int. J. Mol. Sci. 2020, 21(16), 5905; https://doi.org/10.3390/ijms21165905
Received: 16 July 2020 / Revised: 10 August 2020 / Accepted: 14 August 2020 / Published: 17 August 2020
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. View Full-Text
Keywords: 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 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
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MDPI and ACS Style

Ciardulli, M.C.; Marino, L.; Lamparelli, E.P.; Guida, M.; Forsyth, N.R.; Selleri, C.; Della Porta, G.; Maffulli, N. Dose-Response Tendon-Specific Markers Induction by Growth Differentiation Factor-5 in Human Bone Marrow and Umbilical Cord Mesenchymal Stem Cells. Int. J. Mol. Sci. 2020, 21, 5905. https://doi.org/10.3390/ijms21165905

AMA Style

Ciardulli MC, Marino L, Lamparelli EP, Guida M, Forsyth NR, Selleri C, Della Porta G, Maffulli N. 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. 2020; 21(16):5905. https://doi.org/10.3390/ijms21165905

Chicago/Turabian Style

Ciardulli, Maria C., Luigi Marino, Erwin P. Lamparelli, Maurizio Guida, Nicholas R. Forsyth, Carmine Selleri, Giovanna Della Porta, and Nicola Maffulli. 2020. "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 21, no. 16: 5905. https://doi.org/10.3390/ijms21165905

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