Few methods are available to regenerate articular cartilage defects in patients with osteoarthritis. We aimed to assess the safety and efficacy of articular cartilage regeneration by a novel medicinal product composed of allogeneic human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). Patients with Kellgren-Lawrence grade 3 osteoarthritis and International Cartilage Repair Society (ICRS) grade 4 cartilage defects were enrolled in this clinical trial. The stem cell-based medicinal product (a composite of culture-expanded allogeneic hUCB-MSCs and hyaluronic acid hydrogel [Cartistem]) was applied to the lesion site. Safety was assessed by the World Health Organization common toxicity criteria. The primary efficacy outcome was ICRS cartilage repair assessed by arthroscopy at 12 weeks. The secondary efficacy outcome was visual analog scale (VAS) score for pain on walking. During a 7-year extended follow-up, we evaluated safety, VAS score, International Knee Documentation Committee (IKDC) subjective score, magnetic resonance imaging (MRI) findings, and histological evaluations. Seven participants were enrolled. Maturing repair tissue was observed at the 12-week arthroscopic evaluation. The VAS and IKDC scores were improved at 24 weeks. The improved clinical outcomes were stable over 7 years of follow-up. The histological findings at 1 year showed hyaline-like cartilage. MRI at 3 years showed persistence of the regenerated cartilage. Only five mild to moderate treatment-emergent adverse events were observed. There were no cases of osteogenesis or tumorigenesis over 7 years. The application of this novel stem cell-based medicinal product appears to be safe and effective for the regeneration of durable articular cartilage in osteoarthritic knees.

Platelet-rich plasma (PRP) has gained attention as a therapeutic option for knee osteoarthritis; however, its efficacy varies widely. Leukocytes in PRP raise the concern of aggravating proinflammatory activity. To date, PRP has rarely been investigated with regard to leukocyte concentration. To provide clinical evidence of the intra-articular injection of PRPs containing different leukocyte concentrations. Systematic review; Level of evidence, 4. We systematically searched the MEDLINE, Embase, Cochrane Library, CINAHL, and Scopus databases. PRP was classified into leukocyte-poor (LP-PRP) and leukocyte-rich (LR-PRP). Clinical outcomes including Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analog scale (VAS) for pain score, International Knee Documentation Committee (IKDC) subjective score, and adverse reactions were evaluated. The Methodological Index for Non-Randomized Studies criteria were used for quality assessment. Included were 32 studies with an evidence level between 1 and 4. Both LP-PRP and LR-PRP showed improvements above the minimal clinically important difference (MCID) in VAS pain score. No significant intergroup difference was seen at 3, 6, or 12 months of follow-up. Regarding function, both LP-PRP and LR-PRP showed improvements above the MCID in the WOMAC and IKDC scores, with no significant difference between the groups. Adverse reactions for pain were significantly higher in LR-PRP than in LP-PRP (odds ratio, 1.64; 95% confidence interval, 1.29-2.10; P = .01). After intra-articular PRP injection, LR-PRP showed a significantly higher rate of swelling than LP-PRP (odds ratio, 1.56; 95% confidence interval, 1.22-1.99; P = .02). The mean Methodological Index for Non-Randomized Studies score of the included studies was 18.6 (range, 10-24). Intra-articular PRP injection resulted in improvements above the MCID in terms of pain and function in patients with knee osteoarthritis up to 12 months. The risk of local adverse reactions appeared to be increased after LR-PRP compared with LP-PRP injection. The findings of this review can support the potential use of intra-articular PRP injection for the treatment of knee osteoarthritis. In clinical application, clinicians need to consider selecting a specific type of PRP for knee osteoarthritis.

Introduction: The present work was designed to explore the feasibility and efficacy of articular cartilage repair using composites of human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) and four different hydrogels in a rat model. Methods: Full-thickness articular cartilage defects were created at the trochlear groove of femur in both knees of rats. Composites of hUCB-MSCs and four different hydrogels (group A, 4% hyaluronic acid; group B, 3% alginate:30% pluronic (1:1, v/v); group C, 4% hyaluronic acid: 3% alginate: 20% pluronic (2:1:1, v/v}; and group D, 4% hyaluronic acid:3% alginate:20% pluronic;chitosan (4:1:1:2, v/v).) were then transplanted into right knee defect in each study group (five rats/group). Left knees were transplanted with corresponding hydrogels without hUCB-MSCs as controls. At 16 weeks post-transplantation, degrees of cartilage repair were evaluated macroscopically and histologically using Masson’s Trichrome, safranin-O, Sirius red staining, and type-II collagen immunostaining. Results: Overall, group A with 4% hyaluronic acid hydrogel resulted in superior cartilage repair grossly and histologically and achieved a cellular arrangement and collagen organization pattern mimicking adjacent uninjured articular cartilage. Immunostaining and safranin-O staining also revealed that group A displayed the largest areas of type II collagen staining. Sirius red staining revealed that the organization pattern of collagen bundles was more similar to normal cartilage in group A. No evidence of rejection was found. Conclusions: The results of this study suggest that hUCB-MSCs could be used to repair articular cartilage defects in vivo and that hyaluronic acid is an attractive hydrogel candidate for use in combination with hUCB-MSCs.