Development of Standardized Fetal Progenitor Cell Therapy for Cartilage Regenerative Medicine: Industrial Transposition and Preliminary Safety in Xenogeneic Transplantation
Diverse cell therapy approaches constitute prime developmental prospects for managing acute or degenerative cartilaginous tissue affections, synergistically complementing specific surgical solutions. Bone marrow stimulation (i.e., microfracture) remains a standard technique for cartilage repair prom...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/2/250 |
| _version_ | 1797412105421324288 |
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| author | Alexis Laurent Philippe Abdel-Sayed Aurélie Ducrot Nathalie Hirt-Burri Corinne Scaletta Sandra Jaccoud Katja Nuss Anthony S. de Buys Roessingh Wassim Raffoul Dominique Pioletti Brigitte von Rechenberg Lee Ann Applegate Salim Darwiche |
| author_facet | Alexis Laurent Philippe Abdel-Sayed Aurélie Ducrot Nathalie Hirt-Burri Corinne Scaletta Sandra Jaccoud Katja Nuss Anthony S. de Buys Roessingh Wassim Raffoul Dominique Pioletti Brigitte von Rechenberg Lee Ann Applegate Salim Darwiche |
| author_sort | Alexis Laurent |
| collection | DOAJ |
| description | Diverse cell therapy approaches constitute prime developmental prospects for managing acute or degenerative cartilaginous tissue affections, synergistically complementing specific surgical solutions. Bone marrow stimulation (i.e., microfracture) remains a standard technique for cartilage repair promotion, despite incurring the adverse generation of fibrocartilagenous scar tissue, while matrix-induced autologous chondrocyte implantation (MACI) and alternative autologous cell-based approaches may partly circumvent this effect. Autologous chondrocytes remain standard cell sources, yet arrays of alternative therapeutic biologicals present great potential for regenerative medicine. Cultured human epiphyseal chondro-progenitors (hECP) were proposed as sustainable, safe, and stable candidates for chaperoning cartilage repair or regeneration. This study describes the development and industrial transposition of hECP multi-tiered cell banking following a single organ donation, as well as preliminary preclinical hECP safety. Optimized cell banking workflows were proposed, potentially generating millions of safe and sustainable therapeutic products. Furthermore, clinical hECP doses were characterized as non-toxic in a standardized chorioallantoic membrane model. Lastly, a MACI-like protocol, including hECPs, was applied in a three-month GLP pilot safety evaluation in a caprine model of full-thickness articular cartilage defect. The safety of hECP transplantation was highlighted in xenogeneic settings, along with confirmed needs for optimal cell delivery vehicles and implantation techniques favoring effective cartilage repair or regeneration. |
| first_indexed | 2024-03-09T04:57:17Z |
| format | Article |
| id | doaj.art-834c249d992e40e083c4679ce9dd64e3 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T04:57:17Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-834c249d992e40e083c4679ce9dd64e32023-12-03T13:03:56ZengMDPI AGBiomolecules2218-273X2021-02-0111225010.3390/biom11020250Development of Standardized Fetal Progenitor Cell Therapy for Cartilage Regenerative Medicine: Industrial Transposition and Preliminary Safety in Xenogeneic TransplantationAlexis Laurent0Philippe Abdel-Sayed1Aurélie Ducrot2Nathalie Hirt-Burri3Corinne Scaletta4Sandra Jaccoud5Katja Nuss6Anthony S. de Buys Roessingh7Wassim Raffoul8Dominique Pioletti9Brigitte von Rechenberg10Lee Ann Applegate11Salim Darwiche12Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1015 Lausanne, SwitzerlandRegenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1015 Lausanne, SwitzerlandRegenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1015 Lausanne, SwitzerlandRegenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1015 Lausanne, SwitzerlandRegenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1015 Lausanne, SwitzerlandRegenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1015 Lausanne, SwitzerlandMusculoskeletal Research Unit, Zurich Tierspital, University of Zurich, CH-8952 Schlieren, SwitzerlandChildren and Adolescent Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, SwitzerlandPlastic, Reconstructive, and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, SwitzerlandLaboratory of Biomechanical Orthopedics, Ecole Polytechnique Fédérale de Lausanne, CH-2002 Neuchâtel, SwitzerlandMusculoskeletal Research Unit, Zurich Tierspital, University of Zurich, CH-8952 Schlieren, SwitzerlandRegenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1015 Lausanne, SwitzerlandMusculoskeletal Research Unit, Zurich Tierspital, University of Zurich, CH-8952 Schlieren, SwitzerlandDiverse cell therapy approaches constitute prime developmental prospects for managing acute or degenerative cartilaginous tissue affections, synergistically complementing specific surgical solutions. Bone marrow stimulation (i.e., microfracture) remains a standard technique for cartilage repair promotion, despite incurring the adverse generation of fibrocartilagenous scar tissue, while matrix-induced autologous chondrocyte implantation (MACI) and alternative autologous cell-based approaches may partly circumvent this effect. Autologous chondrocytes remain standard cell sources, yet arrays of alternative therapeutic biologicals present great potential for regenerative medicine. Cultured human epiphyseal chondro-progenitors (hECP) were proposed as sustainable, safe, and stable candidates for chaperoning cartilage repair or regeneration. This study describes the development and industrial transposition of hECP multi-tiered cell banking following a single organ donation, as well as preliminary preclinical hECP safety. Optimized cell banking workflows were proposed, potentially generating millions of safe and sustainable therapeutic products. Furthermore, clinical hECP doses were characterized as non-toxic in a standardized chorioallantoic membrane model. Lastly, a MACI-like protocol, including hECPs, was applied in a three-month GLP pilot safety evaluation in a caprine model of full-thickness articular cartilage defect. The safety of hECP transplantation was highlighted in xenogeneic settings, along with confirmed needs for optimal cell delivery vehicles and implantation techniques favoring effective cartilage repair or regeneration.https://www.mdpi.com/2218-273X/11/2/250cartilage cell therapycell bankingchorioallantoic membrane modelfetal progenitor cellslarge animal modelMACI |
| spellingShingle | Alexis Laurent Philippe Abdel-Sayed Aurélie Ducrot Nathalie Hirt-Burri Corinne Scaletta Sandra Jaccoud Katja Nuss Anthony S. de Buys Roessingh Wassim Raffoul Dominique Pioletti Brigitte von Rechenberg Lee Ann Applegate Salim Darwiche Development of Standardized Fetal Progenitor Cell Therapy for Cartilage Regenerative Medicine: Industrial Transposition and Preliminary Safety in Xenogeneic Transplantation Biomolecules cartilage cell therapy cell banking chorioallantoic membrane model fetal progenitor cells large animal model MACI |
| title | Development of Standardized Fetal Progenitor Cell Therapy for Cartilage Regenerative Medicine: Industrial Transposition and Preliminary Safety in Xenogeneic Transplantation |
| title_full | Development of Standardized Fetal Progenitor Cell Therapy for Cartilage Regenerative Medicine: Industrial Transposition and Preliminary Safety in Xenogeneic Transplantation |
| title_fullStr | Development of Standardized Fetal Progenitor Cell Therapy for Cartilage Regenerative Medicine: Industrial Transposition and Preliminary Safety in Xenogeneic Transplantation |
| title_full_unstemmed | Development of Standardized Fetal Progenitor Cell Therapy for Cartilage Regenerative Medicine: Industrial Transposition and Preliminary Safety in Xenogeneic Transplantation |
| title_short | Development of Standardized Fetal Progenitor Cell Therapy for Cartilage Regenerative Medicine: Industrial Transposition and Preliminary Safety in Xenogeneic Transplantation |
| title_sort | development of standardized fetal progenitor cell therapy for cartilage regenerative medicine industrial transposition and preliminary safety in xenogeneic transplantation |
| topic | cartilage cell therapy cell banking chorioallantoic membrane model fetal progenitor cells large animal model MACI |
| url | https://www.mdpi.com/2218-273X/11/2/250 |
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