A Phase I Dose-Escalation Clinical Trial to Assess the Safety and Efficacy of Umbilical Cord-Derived Mesenchymal Stromal Cells in Knee Osteoarthritis

Jose Matas, Cynthia García, Daniela Poblete, Rolando Vernal, Alexander Ortloff, Noymar Luque-Campos, Yessia Hidalgo, Jimena Cuenca, Catalina Infante, Maria Ignacia Cadiz, Maroun Khoury*, Patricia Luz-Crawford*, Francisco Espinoza*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Osteoarthritis (OA) is the most common degenerative joint disease. Mesenchymal stromal cells (MSC) are promising cell-based therapy for OA. However, there is still a need for additional randomized, dose-dependent studies to determine the optimal dose and tissue source of MSC for improved clinical outcomes. Here, we performed a dose-dependant evaluation of umbilical cord (UC)-derived MSC (Celllistem) in a murine model and in knee OA patients. For the preclinical study, a classical dose (200.000 cells) and a lower dose (50.000 cells) of Cellistem were intra-articularly injected into the mice knee joints. The results showed a dose efficacy response effect of Cellistem associated with a decreased inflammatory and degenerative response according to the Pritzker OARSI score. Following the same approach, the dose-escalation phase I clinical trial design included 3 sequential cohorts: low-dose group (2×106 cells), medium-dose group (20×106), and high-dose group (80×106). All the doses were safe, and no serious adverse events were reported. Nonetheless, 100% of the patients injected with the high-dose experienced injection-related swelling in the knee joint. According to WOMAC total outcomes, patients treated with all doses reported significant improvements in pain and function compared with baseline after 3 and 6 months. However, the improvements were higher in patients treated with both medium and low dose as compared to high dose. Therefore, our data demonstrate that the intra-articular injection of different doses of Cellistem is both safe and efficient, making it an interesting therapeutic alternative to treat mild and symptomatic knee OA patients. Trial registration ClinicalTrials.gov NCT03810521.

Original languageEnglish
Pages (from-to)193-203
Number of pages11
JournalStem cells translational medicine
Volume13
Issue number3
DOIs
StatePublished - Mar 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s). Published by Oxford University Press.

Keywords

  • dose escalation
  • murine OA model
  • osteoarthritis
  • phase I clinical trial
  • umbilical-cord-derived mesenchymal stromal cells

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