What is the clinically significant ideal mesenchymal stromal cell count in the management of osteoarthritis of the knee? - Meta-analysis of randomized controlled trials

Sathish Muthu; Ayaz Ali Mir; Rakesh Kumar; Vijendra Yadav; Madhan Jeyaraman; Manish Khanna

doi:10.1016/j.jcot.2021.101744

What is the clinically significant ideal mesenchymal stromal cell count in the management of osteoarthritis of the knee? - Meta-analysis of randomized controlled trials

J Clin Orthop Trauma. 2021 Dec 21:25:101744. doi: 10.1016/j.jcot.2021.101744. eCollection 2022 Feb.

Authors

Sathish Muthu^{1

2

3}, Ayaz Ali Mir^{3

4}, Rakesh Kumar⁵, Vijendra Yadav⁶, Madhan Jeyaraman^{2

3

5}, Manish Khanna³

Affiliations

¹ Department of Orthopaedics, Government Medical College and Hospital, Dindigul, Tamil Nadu, India.
² Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, Uttar Pradesh, India.
³ Indian Stem Cell Study Group (ISCSG) Association, Lucknow, Uttar Pradesh, India.
⁴ Fellow in Orthopaedic Rheumatology, Dr. RML National Law University, Lucknow, Uttar Pradesh, India.
⁵ Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh, India.
⁶ Department of Orthopaedics, Sanjay Gandhi Institute of Trauma & Orthopaedics, Bengaluru, Karnataka, India.

Abstract

Study design: Meta-analysis.

Objectives: We aim to identify the clinically significant ideal Mesenchymal Stem Cell (MSC) count in the management of osteoarthritis of knee from Randomized Controlled Trials (RCTs) available in the literature.

Materials and methods: We conducted independent and duplicate electronic database searches including PubMed, Embase, Web of Science, and Cochrane Library till August 2021 for RCTs conducted in the management of knee osteoarthritis using MSC therapy specifying the quantity of MSCs delivered. We categorized the studies based on the MSC count utilized in them into four groups namely <1 × 10⁷ MSCs (Group I), 1-5x10⁷ MSCs (Group II), 5-10 × 10⁷ MSCs (Group III), and >10 × 10⁷ MSCs (Group IV). Visual Analog Score (VAS) for Pain, Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), Lysholm score, Knee Osteoarthritis Outcome Score (KOOS), and adverse events were the outcomes analyzed. Analysis was performed in R-platform using OpenMeta [Analyst] software.

Results: 14 studies involving 564 patients were included for analysis. We noted incremental decrease in the VAS with increasing dosage of MSCs at 12 months [Group I,WMD = 2.641(p = 0.854); Group II, WMD = -4.853(p = 0.379); Group III, WMD = -12.154 (p = 0.316); Group IV, WMD = -15.935(p = 0.116)], and 24 months [Group I,WMD = -6(p = 0.001); Group II, WMD = -15(p = 0.001); Group IV, WMD = -20(p = 0.001)]. We also noted incremental improvement in the WOMAC, KOOS with increasing dosage of MSCs at 12 months [Group I, WMD = 7(p = 0.001); Group II, WMD = 28(p = 0.001); Group IV, WMD = 30(p = 0.001)] and [Group II, WMD = -2.562(p = 0.676); Group III, WMD = 7.670(p = 0.099); Group IV, WMD = 13.475(p = 0.261)] respectively. However, we noted significant reduction in the Lysholm score in Group IV, compared to the others at 12 months (WMD = -12.5, 95%CI[-25.883,0.883]) and 24 months (WMD = -6.6, 95%CI[-23.596,10.396]). We did not find any significant increase in the adverse events with incremental dosage of MSCs in any of the groups compared.

Conclusion: Compared to the four dosage groups of MSCs analyzed, Group III showed consistent significant improvement in pain and functional outcomes analyzed compared to the other groups. Hence, we recommend a cell volume of 5-10 × 10⁷ cells to be delivered to the target site to obtain superior benefits out of the procedure. However, we urge future trials of sufficient quality to validate our findings to arrive at a consensus on the ideal count of MSCs to be delivered in the cellular therapy for knee osteoarthritis.

Keywords: Bone-marrow derived mesenchymal stem cell; Cartilage regeneration; Cell count; Knee osteoarthritis; Mesenchymal stem cell; Meta-analysis.

Publication types

Review