1. Preclinical Development of a Therapy for Chronic Traumatic Spinal Cord Injury in Rats Using Human Wharton's Jelly Mesenchymal Stromal Cells : Proof of Concept and Regulatory Compliance
- Author
-
Joaquim Vives, Joaquim Hernández, Clémentine Mirabel, Maria Puigdomenech-Poch, David Romeo-Guitart, Sara Marmolejo-Martínez-Artesero, Raquel Cabrera-Pérez, Jessica Jaramillo, Hatice Kumru, Joan García-López, Joan Vidal-Samsó, Xavier Navarro, Ruth Coll-Bonet, Institut Català de la Salut, [Vives J] Banc de Sang i Teixits, Barcelona, Spain. Grup de Recerca en Enginyeria Tissular Musculoesquelètica, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Hernández J, Puigdomenech-Poch M, Romeo-Guitart D, Marmolejo-Martínez-Artesero S] Institut de Neurociències, Departament de Biologia Cel•lular, Fisiologia i Immunologia, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Mirabel C, Marmolejo-Martínez-Artesero S] Banc de Sang i Teixits, Barcelona, Spain. Grup de Recerca en Enginyeria Tissular Musculoesquelètica, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
cell-based therapy ,tejidos::tejido conectivo::gelatina de Wharton [ANATOMÍA] ,Medul·la espinal - Ferides i lesions - Tractament ,Umbilical Cord ,mesenchymal stromal cells ,translational medicine ,cell therapy ,stem cells ,spinal cord injury ,animal model ,preclinical research ,advanced therapy ,good laboratory practice ,Animals ,Humans ,Wharton Jelly ,células::células del tejido conectivo::células del estroma::células madre mesenquimatosas [ANATOMÍA] ,enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades de la médula espinal::traumatismos de la médula espinal [ENFERMEDADES] ,Cells::Connective Tissue Cells::Stromal Cells::Mesenchymal Stem Cells [ANATOMY] ,Cells, Cultured ,Spinal Cord Injuries ,Otros calificadores::/terapia [Otros calificadores] ,Teixit connectiu ,Mesenchymal Stem Cells ,Cèl·lules mare mesenquimàtiques ,General Medicine ,Other subheadings::/therapy [Other subheadings] ,Rats ,Nervous System Diseases::Central Nervous System Diseases::Spinal Cord Diseases::Spinal Cord Injuries [DISEASES] ,Tissues::Connective Tissue::Wharton Jelly [ANATOMY] - Abstract
Animal model; Cell therapy; Mesenchymal stromal cells Modelo animal; Terapia celular; Células estromales mesenquimales Model animal; Teràpia cel·lular; Cèl·lules estromals mesenquimàtiques Background: the use of Mesenchymal Stromal Cells (MSC) in emerging therapies for spinal cord injury (SCI) hold the potential to improve functional recovery. However, the development of cell-based medicines is challenging and preclinical studies addressing quality, safety and efficacy must be conducted prior to clinical testing; (2) Methods: herein we present (i) the characterization of the quality attributes of MSC from the Wharton’s jelly (WJ) of the umbilical cord, (ii) safety of intrathecal infusion in a 3-month subchronic toxicity assessment study, and (iii) efficacy in a rat SCI model by controlled impaction (100 kdynes) after single (day 7 post-injury) and repeated dose of 1 × 106 MSC,WJ (days 7 and 14 post-injury) with 70-day monitoring by electrophysiological testing, motor function assessment and histology evaluation; (3) Results: no toxicity associated to MSC,WJ infusion was observed. Regarding efficacy, recovery of locomotion was promoted at early time points. Persistence of MSC,WJ was detected early after administration (day 2 post-injection) but not at days 14 and 63 post-injection. (4) Conclusions: the safety profile and signs of efficacy substantiate the suitability of the presented data for inclusion in the Investigational Medicinal Product Dossier for further consideration by the competent Regulatory Authority to proceed with clinical trials. This work has been developed in the context of the Spanish Cell Therapy Network (TerCel, expedient No.’s RD16/0011/0014, RD16/0011/0028 and RD16/00111/0036) and supported by Fundació La Marató de TV3 (grant No. 616/2012) and BST internal funding. Work in J.G.-L.’s laboratory is supported by the Spanish Advanced Therapy Network funded by Ministerio de Ciencia Innovación y Universidades de España (Instituto de Salud Carlos III (TERAV, expedient No.’s RD21/0017/0008 and RD21/0017/0022), CIBERNED (CB06/05/1105), and J.V.’s laboratory is a Consolidated Research Group (ref. 2017SGR719) by the Generalitat de Catalunya.
- Published
- 2022