Outcomes of High Tibial Osteotomy With Versus Without Mesenchymal Stem Cell Augmentation: A Systematic Review and Meta-analysis

Abstract

Background: The outcomes after high tibial osteotomy (HTO) with augmentation of intra-articular mesenchymal stem cell (MSCs) for medial tibiofemoral osteoarthritis remain controversial. Purpose: To pool existing studies to compare the outcomes of HTO with versus without intra-articular MSC augmentation when performed for medial tibiofemoral osteoarthritis. Study Design: Systematic review; Level of evidence, 3. Methods: The systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Included were clinical studies that compared the outcomes of HTO with intra-articular MSC augmentation (MSC group) versus without (control group). Pre- and postoperative outcomes were compared between groups from measures including the Lysholm score, International Knee Documentation Committee (IKDC) score, Knee injury and Osteoarthritis Outcome Score, Hospital for Special Surgery Knee Rating Scale, Tegner score, visual analog scale for pain, arthroscopic and histological grading scales, femorotibial angle, weightbearing line, and posterior tibial slope. Results: We reviewed 4 studies with a total of 224 patients. The MSC group demonstrated significantly greater improvement versus controls in the pooled Lysholm score (weighted mean difference [WMD], 6.64; 95% CI, 0.90 to 12.39) and pooled IKDC score (WMD, 9.21; 95% CI, 4.06 to 14.36), which were within or close to the minimal clinically important difference. Radiological outcomes were similar in both groups, including the femorotibial angle (WMD, –0.01; 95% CI, –1.10 to 1.09), weightbearing line, and posterior tibial slope. The studies were homogeneous, and no publication bias was noted. Conclusion: Intra-articular MSC augmentation for HTO may modestly improve functional outcomes as compared with HTO alone. However, adequate data are lacking to make definitive conclusions regarding the effect of MSC augmentation on pain or arthroscopic and histologic grading.

Intra-articular Injection of Mesenchymal Stem Cells After High Tibial Osteotomy in Osteoarthritic Knee: Two-Year Follow-up of Randomized Control Trial

“…The main finding of this RCT was that intra-articular injection of autologous ADMSCs after MOWHTO showed better results than MOWHTO alone in OA knee with varus malalignment, with respect to cartilage regeneration and modest functional improvement without relevant AEs and complications until postoperative 2-year follow-up. Although few comparative studies have investigated cartilage regeneration and clinical efficacy of intra-articular injection of MSCs to MOWHTO, 12 , 25 , 26 no RCT has been performed with serial MRI evaluations and assessment of macroscopic cartilage changes.…”

“…The primary etiology of knee OA is characterized by biomechanical and biochemical changes in the knee joint including the destructive course of articular cartilage. 2 , 10 , 12 In a biomechanical aspect of the OA knee, since most knees with OA have various degrees of varus malalignment, excessive medial contact stress results in a meniscal degenerative tear and marked cartilage wear with varus progression which may induce incapability to tolerate excessive contact pressure and joint destruction. 13 , 14 In the biochemical aspect, the following phenomenon can accelerate arthritic conditions such as a restricted supply of nutrients and oxygen, insufficient synthesis of extracellular matrix components, increased catabolic cytokines, apoptosis of chondrocytes, and synovial inflammation.…”

“…In this regard, concomitant MSCs-based therapy with MOWHTO has recently emerged with the hope to improve the biochemical environment in addition to biomechanical correction. 12 Several studies investigated the functional outcomes, cartilage regeneration, and safety of intra-articular injection of MSCs with MOWHTO. 12 , 25 , 26 , 62 Since their study design was not that advanced, only one RCT has been reported among the studies.…”

“…The primary pathogenesis of knee OA involves alteration of the biomechanical and biochemical environment in the joint which leads to a destructive process in cartilage. 2 , 10 , 12 Among biomechanical environments, varus malalignment is the most common deformity and is highly associated with progressing medial compartmental OA, because it potentially induces excessive contact pressure on the medial side of the varus knee which accelerates wear and degradation of articular cartilage. 13 , 14 Therefore, realignment surgery such as medial open-wedge high-tibial-osteotomy(MOWHTO) has been introduced to provide a favorable biomechanical environment by lateral shifting of weight load and showed effective clinical results to postpone joint replacement surgery.…”

“…With a desire to challenge the nature of knee OA, intra-articular MSC-based therapy with MOWHTO in varus knee has been attempted lately, given the efficacy of regenerative medicine would be enhanced when coupled with biomechanical correction by the osteotomy. 10 , 12 Although several studies have shown the efficacy of MOWHTO concomitant with intra-articular injection of MSCs, 25-27 as for the RCT study, only one with bone marrow-derived MSCs exists with some limitations. 26 The trial had performed MOWHTO with additional cartilage repair procedure(microfracture) and evaluated a single magnetic resonance imaging(MRI) assessment at postoperative 1 year without preoperative MRI, which might be critical confound factors for assessing articular cartilage changes.…”