Allogenic umbilical cord blood-derived mesenchymal stromal cell implantation was superior to bone marrow aspirate concentrate augmentation for cartilage regeneration despite similar clinical outcomes

Abstract

PurposeThe aim of this study was to compare clinical and second‐look arthroscopic outcomes between bone marrow aspirate concentrate (BMAC) augmentation and human umbilical cord blood‐derived mesenchymal stromal cell (hUCB‐MSC) implantation in high tibial osteotomy (HTO) for medial compartmental knee osteoarthritis and identify the relationship between articular cartilage regeneration and HTO outcomes. MethodsA total of 176 patients who underwent HTO combined with a BMAC or hUCB‐MSC procedure for medial compartment osteoarthritis (Kellgren–Lawrence grade 3) between June 2014 and September 2018 with a minimum follow‐up of 2 years were reviewed. After HTO, multiple holes were drilled at cartilage defect sites of the medial femoral condyle (MFC), and then prepared BMAC or hUCB‐MSCs in combination with scaffolds were implanted in the MFC lesions. After propensity score matching based on sex, age, body mass index, and lesion size, 55 patients in each of the BMAC and hUCB‐MSC groups were successfully matched. Second‐look arthroscopic findings were assessed according to the International Cartilage Repair Society (ICRS) Cartilage Repair Assessment (CRA) grading system and Koshino staging system. Clinical outcomes were evaluated using the International Knee Documentation Committee (IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS), Short‐Form 36 (SF‐36), and Tegner activity scores. ResultsAt a mean follow‐up of 33 months, clinical outcomes including IKDC, KOOS, SF‐36, and Tegner activity scores were significantly improved in both groups (p < 0.001); however, there were no differences between the two groups. Second‐look arthroscopy showed better healing of regenerated cartilage in the hUCB‐MSC group (Grade I [4 cases, 9.1%]; Grade II [30 cases, 68.2%]; Grade III [11 cases, 22.7%]) than in the BMAC group (Grade I [1 case, 2.7%]; Grade II [20 cases, 54.1%]; Grade III [11 cases, 29.7%]; Grade IV [5 cases, 13.5%]) according to the ICRS CRA grading system (p = 0.040). There was no significant intergroup difference in terms of defect coverage based on the Koshino staging system (p = 0.057). Moreover, ICRS CRA grades at second‐look arthroscopy were significantly correlated with clinical outcomes (r = − 0.337; p = 0.002). ConclusionThere were no significant differences in the clinical outcomes between the two groups. Both treatments provided similar, reliable outcomes in terms of pain relief, functional scores, and quality of life at a mean follow‐up of 33 months. However, hUCB‐MSC implantation was more effective than BMAC augmentation for articular cartilage regeneration.

Potential New Treatments for Knee OA: A Prospective Review of Registered Trials

“…The effect was superior to HA [35]. For patients receiving high tibial osteotomy, the intraarticular addition of bone marrow aspirate concentrate or human umbilical cord blood-derived MSCs provided similar, outcomes in terms of pain relief, functional scores, and quality of life at a mean follow-up of 33 months [36].…”

The Hunt Is On! In Pursuit of the Ideal Stem Cell Population for Cartilage Regeneration

“…Such heterogeneity exists in studies using various animal models of OA in preclinical studies ( Cope et al, 2019 ; Wang et al, 2022 ), as well as clinical trials. Despite these limitations, several clinical trials have recently reported on the efficacy of exogenous MSCs to regenerate cartilage in OA ( Table 1 ) ( Emadedin et al, 2018 ; Kuah et al, 2018 ; Freitag et al, 2019 ; Khalifeh Soltani et al, 2019 ; Lee et al, 2019 ; Lu et al, 2019 ; Matas et al, 2019 ; Shapiro et al, 2019 ; Anz et al, 2020 ; Yang et al, 2022 ). Across these trials, methodologic heterogeneity has hindered a standardized approach to MSC-based therapies, including the use of host source (allogeneic vs. autologous), tissue source (bone marrow, adipose, umbilical cord, and placenta), injectate (tissue concentrates vs. isolated MSCs), whether they were expanded in vitro prior to injection, the dosage used, and the delivery method (e.g., image-guided or not).…”

“…Similarly, the tissue of origin of exogenous MSCs transplanted into the site of cartilage injury will also be a primary factor toward successful cartilage regeneration. Interestingly, while studies have compared stem cell chondrogenic capacity from different niches in vitro ( Mochizuki et al, 2006 ; Koga et al, 2008 ), and studies have compared stem cells to implanted chondrocytes ( Nejadnik et al, 2010 ) and bone marrow concentrate ( Yang et al, 2022 ) in vivo , we are not aware of any in vivo studies directly comparing chondrogenic repair capacities of different stem cell populations derived from different tissue sources. To date, clinical trials evaluating MSCs have shown some evidence of reducing OA-associated pain and can produce cartilage in vitro , but there is little evidence that current MSC treatment regenerates damaged cartilage in vivo .…”

Cell Sources for Cartilage Repair—Biological and Clinical Perspective

“…The patients were followed for a minimum of one year, and at the final follow-up, the median IKDC subjective score, the WOMAC score, the KSS pain and function scores, and the HSS improved significantly. Yang et al [ 119 ] compared clinical and second-look arthroscopic outcomes between bone marrow aspirate concentrate (BMAC) augmentation and UC-MSCs transplantation in HTO for medial compartmental knee OA. At a mean follow-up of 33 months, clinical outcomes including IKDC, KOOS, SF-36, and Tegner activity scores were significantly improved in both groups, but there were no differences between the two groups.…”