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

Abstract

(1) 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.

Study of Combinatorial Cell Therapy and Neuroprotective Agents for the Treatment of Spinal Cord Injury in Experimental Models

“…Thus, we confirmed that both the biomaterial and the implantation procedure represent a safe therapy for transplantation in our short-term study. Furthermore, the biomaterial did not impede the migration of the cell transplants to the lesion site, similar to previous studies in which cell therapy was transplanted by intrathecal injections in preclinical models (T.-T. Cao et al 2022;Vives et al 2022). However, long-term studies should be carried out to study the long-term safety and outcomes of this non-invasive approach.…”

Refinement of the motorised laminectomy-assisted rat spinal cord injury model by analgesic treatment

“…In animal experimentation for SCI studies, the use of post-operative analgesics appears to be highly uncommon [47][48][49][50]. Further, studies that do report usage of analgesia often provide minimal details on duration of therapy [51] and frequency of administration, or report non-validated analgesic regimens [52] that could be inadequate [53,54]. Further, several systematic reviews done on animal models of SCI has also overlooked the importance of usage, reporting, and risk of potential side-effects of analgesics on research data, if any [38, 43,55].…”