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.

The cartilage regeneration potential of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) with a hyaluronic acid (HA) hydrogel composite has shown remarkable results in rat and rabbit models. The purpose of the present study was to confirm the consistent regenerative potential in a pig model using three different cell lines. A full-thickness chondral injury was intentionally created in the trochlear groove of each knee in 6 minipigs. Three weeks later, an osteochondral defect, 5 mm wide by 10 mm deep, was created, followed by an 8-mm-wide and 5-mm-deep reaming. A mixture (1.5 ml) of hUCB-MSCs (0.5 × 107 cells per milliliter) and 4% HA hydrogel composite was then transplanted into the defect on the right knee. Each cell line was used in two minipigs. The osteochondral defect created in the same manner on the left knee was untreated to act as the control. At 12 weeks postoperatively, the pigs were sacrificed, and the degree of subsequent cartilage regeneration was evaluated by gross and histological analysis. The transplanted knee resulted in superior and more complete hyaline cartilage regeneration compared with the control knee. The cellular characteristics (e.g., cellular proliferation and chondrogenic differentiation capacity) of the hUCB-MSCs influenced the degree of cartilage regeneration potential. This evidence of consistent cartilage regeneration using composites of hUCB-MSCs and HA hydrogel in a large animal model could be a stepping stone to a human clinical trial in the future. Significance: To date, several studies have investigated the chondrogenic potential of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs); however, the preclinical studies are still limited in numbers with various results. In parallel, in the past several years, the cartilage regeneration potential of hUCB-MSCs with a hyaluronic acid (HA) hydrogel composite have been investigated and remarkable results in rat and rabbit models have been attained. (These experimental results are currently in preparation for publication.) Before applying the cartilage regeneration technique in a human clinical trial, it seemed necessary to confirm the consistent result in a larger animal model. At 12 weeks postoperatively, the minipigs were sacrificed, and the degree of subsequent cartilage regeneration was evaluated by gross and histological analysis. The transplanted knee resulted in superior and more complete hyaline cartilage regeneration compared with the control knee. This evidence of consistent cartilage regeneration with composites of hUCB-MSCs and HA hydrogel in a large animal model could be a stepping stone to a human clinical trial in the future.

Moon ES, et al. Yonsei Med J. 2007 Aug;48(4):645-652. http://dx.doi.org/10.3349/ymj.2007.48.4.645