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Sequential growth factor exposure of human Ad‑MSCs improves chondrogenic differentiation in an osteochondral biphasic implant

  • Authors:
    • Alejandro Garcia‑Ruiz
    • Celia N. Sánchez‑Domínguez
    • Nidia K. Moncada‑Saucedo
    • Vanessa Pérez‑Silos
    • Jorge Lara‑Arias
    • Iván A. Marino‑Martínez
    • Alberto Camacho‑Morales
    • Víktor J. Romero‑Diaz
    • Víctor Peña‑Martinez
    • Rosalío Ramos‑Payán
    • Yanko Castro‑Govea
    • Rocky S. Tuan
    • Hang Lin
    • Lizeth Fuentes‑Mera
    • Ana María Rivas‑Estilla
  • View Affiliations / Copyright

    Affiliations: Biochemistry and Molecular Medicine Department, Faculty of Medicine and University Hospital ‘Dr José E. González’, Autonomous University of Nuevo Leon, Monterrey, Nuevo Leon 64460, Mexico, Orthopedics and Traumatology Service, Faculty of Medicine and University Hospital ‘Dr José E. González’, Autonomous University of Nuevo Leon, Monterrey, Nuevo Leon 64460, Mexico, Pathology Department, Faculty of Medicine and University Hospital ‘Dr José E. González’, Autonomous University of Nuevo Leon, Monterrey, Nuevo Leon 64460, Mexico, Histology Department, Faculty of Medicine and University Hospital ‘Dr José E. González’, Autonomous University of Nuevo Leon, Monterrey, Nuevo Leon 64460, Mexico, Microbiology Laboratory, Faculty of Chemical‑Biological Sciences, Autonomous University of Sinaloa, Culiacan, Sinaloa 80040, Mexico, Plastic Surgery Department, Faculty of Medicine and University Hospital ‘Dr José E. González’, Autonomous University of Nuevo Leon, Monterrey, Nuevo Leon 64460, Mexico, Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA, Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA 15219, USA
    Copyright: © Garcia‑Ruiz et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 1282
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    Published online on: September 13, 2021
       https://doi.org/10.3892/etm.2021.10717
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Abstract

Joint cartilage damage affects 10‑12% of the world's population. Medical treatments improve the short‑term quality of life of affected individuals but lack a long‑term effect due to injury progression into fibrocartilage. The use of mesenchymal stem cells (MSCs) is one of the most promising strategies for tissue regeneration due to their ability to be isolated, expanded and differentiated into metabolically active chondrocytes to achieve long‑term restoration. For this purpose, human adipose‑derived MSCs (Ad‑MSCs) were isolated from lipectomy and grown in xeno‑free conditions. To establish the best differentiation potential towards a stable chondrocyte phenotype, isolated Ad‑MSCs were sequentially exposed to five differentiation schemes of growth factors in previously designed three‑dimensional biphasic scaffolds with incorporation of a decellularized cartilage matrix as a bioactive ingredient, silk fibroin and bone matrix, to generate a system capable of being loaded with pre‑differentiated Ad‑MSCs, to be used as a clinical implant in cartilage lesions for tissue regeneration. Chondrogenic and osteogenic markers were analyzed by reverse transcription‑quantitative PCR and cartilage matrix generation by histology techniques at different time points over 40 days. All groups had an increased expression of chondrogenic markers; however, the use of fibroblast growth factor 2 (10 ng/ml) followed by a combination of insulin‑like growth factor 1 (100 ng/ml)/TGFβ1 (10 ng/ml) and a final step of exposure to TGFβ1 alone (10 ng/ml) resulted in the most optimal chondrogenic signature towards chondrocyte differentiation and the lowest levels of osteogenic expression, while maintaining stable collagen matrix deposition until day 33. This encourages their possible use in osteochondral lesions, with appropriate properties for use in clinical patients.
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Copy and paste a formatted citation
Spandidos Publications style
Garcia‑Ruiz A, Sánchez‑Domínguez CN, Moncada‑Saucedo NK, Pérez‑Silos V, Lara‑Arias J, Marino‑Martínez IA, Camacho‑Morales A, Romero‑Diaz VJ, Peña‑Martinez V, Ramos‑Payán R, Ramos‑Payán R, et al: Sequential growth factor exposure of human Ad‑MSCs improves chondrogenic differentiation in an osteochondral biphasic implant. Exp Ther Med 22: 1282, 2021.
APA
Garcia‑Ruiz, A., Sánchez‑Domínguez, C.N., Moncada‑Saucedo, N.K., Pérez‑Silos, V., Lara‑Arias, J., Marino‑Martínez, I.A. ... Rivas‑Estilla, A.M. (2021). Sequential growth factor exposure of human Ad‑MSCs improves chondrogenic differentiation in an osteochondral biphasic implant. Experimental and Therapeutic Medicine, 22, 1282. https://doi.org/10.3892/etm.2021.10717
MLA
Garcia‑Ruiz, A., Sánchez‑Domínguez, C. N., Moncada‑Saucedo, N. K., Pérez‑Silos, V., Lara‑Arias, J., Marino‑Martínez, I. A., Camacho‑Morales, A., Romero‑Diaz, V. J., Peña‑Martinez, V., Ramos‑Payán, R., Castro‑Govea, Y., Tuan, R. S., Lin, H., Fuentes‑Mera, L., Rivas‑Estilla, A. M."Sequential growth factor exposure of human Ad‑MSCs improves chondrogenic differentiation in an osteochondral biphasic implant". Experimental and Therapeutic Medicine 22.5 (2021): 1282.
Chicago
Garcia‑Ruiz, A., Sánchez‑Domínguez, C. N., Moncada‑Saucedo, N. K., Pérez‑Silos, V., Lara‑Arias, J., Marino‑Martínez, I. A., Camacho‑Morales, A., Romero‑Diaz, V. J., Peña‑Martinez, V., Ramos‑Payán, R., Castro‑Govea, Y., Tuan, R. S., Lin, H., Fuentes‑Mera, L., Rivas‑Estilla, A. M."Sequential growth factor exposure of human Ad‑MSCs improves chondrogenic differentiation in an osteochondral biphasic implant". Experimental and Therapeutic Medicine 22, no. 5 (2021): 1282. https://doi.org/10.3892/etm.2021.10717
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Spandidos Publications style
Garcia‑Ruiz A, Sánchez‑Domínguez CN, Moncada‑Saucedo NK, Pérez‑Silos V, Lara‑Arias J, Marino‑Martínez IA, Camacho‑Morales A, Romero‑Diaz VJ, Peña‑Martinez V, Ramos‑Payán R, Ramos‑Payán R, et al: Sequential growth factor exposure of human Ad‑MSCs improves chondrogenic differentiation in an osteochondral biphasic implant. Exp Ther Med 22: 1282, 2021.
APA
Garcia‑Ruiz, A., Sánchez‑Domínguez, C.N., Moncada‑Saucedo, N.K., Pérez‑Silos, V., Lara‑Arias, J., Marino‑Martínez, I.A. ... Rivas‑Estilla, A.M. (2021). Sequential growth factor exposure of human Ad‑MSCs improves chondrogenic differentiation in an osteochondral biphasic implant. Experimental and Therapeutic Medicine, 22, 1282. https://doi.org/10.3892/etm.2021.10717
MLA
Garcia‑Ruiz, A., Sánchez‑Domínguez, C. N., Moncada‑Saucedo, N. K., Pérez‑Silos, V., Lara‑Arias, J., Marino‑Martínez, I. A., Camacho‑Morales, A., Romero‑Diaz, V. J., Peña‑Martinez, V., Ramos‑Payán, R., Castro‑Govea, Y., Tuan, R. S., Lin, H., Fuentes‑Mera, L., Rivas‑Estilla, A. M."Sequential growth factor exposure of human Ad‑MSCs improves chondrogenic differentiation in an osteochondral biphasic implant". Experimental and Therapeutic Medicine 22.5 (2021): 1282.
Chicago
Garcia‑Ruiz, A., Sánchez‑Domínguez, C. N., Moncada‑Saucedo, N. K., Pérez‑Silos, V., Lara‑Arias, J., Marino‑Martínez, I. A., Camacho‑Morales, A., Romero‑Diaz, V. J., Peña‑Martinez, V., Ramos‑Payán, R., Castro‑Govea, Y., Tuan, R. S., Lin, H., Fuentes‑Mera, L., Rivas‑Estilla, A. M."Sequential growth factor exposure of human Ad‑MSCs improves chondrogenic differentiation in an osteochondral biphasic implant". Experimental and Therapeutic Medicine 22, no. 5 (2021): 1282. https://doi.org/10.3892/etm.2021.10717
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