A Phase I Dose-Escalation Clinical Trial to Assess the Safety and Efficacy of Umbilical Cord-Derived Mesenchymal Stromal Cells in Knee Osteoarthritis
- PMID: 38366909
- PMCID: PMC10940813
- DOI: 10.1093/stcltm/szad088
A Phase I Dose-Escalation Clinical Trial to Assess the Safety and Efficacy of Umbilical Cord-Derived Mesenchymal Stromal Cells in Knee Osteoarthritis
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.
Keywords: dose escalation; murine OA model; osteoarthritis; phase I clinical trial; umbilical-cord-derived mesenchymal stromal cells.
© The Author(s) 2024. Published by Oxford University Press.
Conflict of interest statement
Maroun Khoury reports receiving grants from ANID, during the conduct of the study and other from Cells for Cells. In addition, Dr. Khoury is the inventor of patents related to mesenchymal stem cells including a patent WO2014135924A1 pending, a patent WO2017064670A2 pending, a patent WO2017064672A1 pending, and a patent WO/2019/051623 pending.
Figures
![Graphical Abstract](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/10940813/bin/szad088_fig5.gif)
![Figure 1.](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/10940813/bin/szad088_fig1.gif)
![Figure 2.](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/10940813/bin/szad088_fig2.gif)
![Figure 3.](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/10940813/bin/szad088_fig3.gif)
![Figure 4.](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/10940813/bin/szad088_fig4.gif)
Similar articles
-
Umbilical Cord-Derived Mesenchymal Stromal Cells (MSCs) for Knee Osteoarthritis: Repeated MSC Dosing Is Superior to a Single MSC Dose and to Hyaluronic Acid in a Controlled Randomized Phase I/II Trial.Stem Cells Transl Med. 2019 Mar;8(3):215-224. doi: 10.1002/sctm.18-0053. Epub 2018 Dec 28. Stem Cells Transl Med. 2019. PMID: 30592390 Free PMC article. Clinical Trial.
-
Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial.Stem Cells Transl Med. 2016 Jul;5(7):847-56. doi: 10.5966/sctm.2015-0245. Epub 2016 May 23. Stem Cells Transl Med. 2016. PMID: 27217345 Free PMC article. Clinical Trial.
-
Clinical Efficacy of Intra-articular Mesenchymal Stromal Cells for the Treatment of Knee Osteoarthritis: A Double-Blinded Prospective Randomized Controlled Clinical Trial.Am J Sports Med. 2020 Mar;48(3):588-598. doi: 10.1177/0363546519899923. Am J Sports Med. 2020. PMID: 32109160 Clinical Trial.
-
Injective mesenchymal stem cell-based treatments for knee osteoarthritis: from mechanisms of action to current clinical evidences.Knee Surg Sports Traumatol Arthrosc. 2019 Jun;27(6):2003-2020. doi: 10.1007/s00167-018-5118-9. Epub 2018 Aug 29. Knee Surg Sports Traumatol Arthrosc. 2019. PMID: 30159741 Free PMC article. Review.
-
Intra-articular injection choice for osteoarthritis: making sense of cell source-an updated systematic review and dual network meta-analysis.Arthritis Res Ther. 2022 Nov 28;24(1):260. doi: 10.1186/s13075-022-02953-0. Arthritis Res Ther. 2022. PMID: 36443838 Free PMC article. Review.
References
-
- Han S. Osteoarthritis year in review 2022: Biology. Osteoarthritis Cartilage. 2022;30(12):1575-1582. - PubMed
-
- Gupta PK, Chullikana A, Rengasamy M, et al. . Efficacy and safety of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel®): preclinical and clinical trial in osteoarthritis of the knee joint. Arthritis Res Ther. 2016;18(1):301. 10.1186/s13075-016-1195-7 - DOI - PMC - PubMed