Repair of Full-Thickness Cartilage Defects With Cells of Different Origin in a Rabbit Model

doi:10.1016/j.arthro.2006.09.005

Arthroscopy: The Journal of Arthroscopic & Related Surgery

Volume 23, Issue 2, February 2007, Pages 178-187

https://doi.org/10.1016/j.arthro.2006.09.005 Get rights and content

Purpose: The purpose of this study was to evaluate the repaired tissues formed in full-thickness cartilage defects in a rabbit model implanted with 4 types of chondrogenic cells, including chondrocytes, mesenchymal stem cells (MSCs) and fibroblasts from rabbit, and human umbilical cord blood (hUCB) stem cells. Methods: Chondrocytes, MSCs, and fibroblasts were isolated from 6-week-old New Zealand rabbits; hUCB stem cells were isolated from the umbilical cord blood of newborn children. These 4 types of cells were cultured in vitro and embedded in polylactic acid (PLA) matrices. Full-thickness defects were produced in the femoral trochlear grooves of both knees in 36 adult New Zealand White rabbits. Cell/PLA composites were transplanted into cartilage defects. A total of 5 groups were formed according to implanted cell type: Group A, chondrocytes; Group B, MSCs; Group C, fibroblasts; Group D, hUCB stem cells; and Group E, no cells (control group). Repaired tissues were evaluated grossly, histologically, and immunohistochemically at 6 weeks and 12 weeks after implantation. Results: In Groups A and B, defects were repaired with hyaline-like cartilage. In Group C, defects were repaired with fibrous tissue. In Group D, defects were repaired primarily with fibrous tissue and scattered chondrocytes; in some specimens, defects were repaired with a thin layer of hyaline-like cartilage at 12 weeks. In Group E, defects were repaired with fibrous tissue. Histologic scores in Groups A and B were significantly higher than those in Groups C, D, and E at 6 and 12 weeks after transplantation. Conclusions: Full-thickness cartilage defects treated with chondrocyte or MSC transplantation were repaired with hyaline-like cartilage tissue, and repair was significantly better than in tissues treated with fibroblasts and hUCB stem cells, as well as in the control group. Repaired tissues treated with MSCs appeared to have better cell arrangement, subchondral bone remodeling, and integration with surrounding cartilage than did repaired tissues generated by chondrocyte implantation. MSCs might be the most suitable cell source for cartilage repair. Further investigation into hUCB stem cell transplantation is needed. Clinical Relevance: In our study of rabbits, MSCs supplied the most promising cell source for cartilage repair.

Section snippets

Methods

Experimental rabbits were kept in research facilities for laboratory animal science at our university. The research protocol of this experiment was reviewed and approved by the ethics committee of the university.

Macroscopic Findings

In the chondrocyte and MSC groups, no difference was observed in the appearance of defects. At 6 weeks after implantation, grafted areas were covered with smooth, white semitransparent tissue; margins of the grafted areas were recognizable. At 12 weeks after implantation, repaired tissues became opaque and were well incorporated. It was difficult to discern the boundary between the host and the repaired tissue. No apparent synovitis was observed.

In the hUCB stem cell group, at 6 weeks after

Discussion

Progress in cell biology and biomaterial technology has led to the possibility of therapeutic applications of tissue engineering for the repair of cartilage defects. Tissue engineering techniques for cartilage repair have been given much attention in the orthopaedic field. A lot of basic research for articular cartilage repair through the tissue engineering technique has been conducted.7, 8, 9, 10, 11, 12, 13, 14 The cell source has been a big challenge for this tissue engineering approach.

Conclusions

Full-thickness defects treated with chondrocyte or MSC transplantation were repaired with hyaline-like cartilage tissue, and repaired tissue was significantly better than that attained with fibroblast or hUCB stem cell treatment; they were also better than those observed in the control group. Repaired tissue treated with MSCs appeared to yield cell arrangement, subchondral bone remodeling, and integration with surrounding cartilage that were superior to those seen in repaired tissue generated

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The aim of this systematic review was to assess the effects of stem cell-based therapies on the treatment of Temporomandibular Joint Osteoarthritis (TMJ-OA) and the regeneration of cartilage/osteochondral defects.
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After applying the inclusion and exclusion criteria, 10 studies were included in the qualitative synthesis. Regardless of cell origin, stem cell-based therapeutic approaches induced protective, anti-inflammatory, and chondroregenerative potential in the treatment of TMJ-OA. Regeneration of the cartilage layer on the surface of the condyle was achieved when stem cells were directly flushed into the defect or when delivered within a carrier.
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Intra-Articular Mesenchymal Stromal Cell Injections Are No Different From Placebo in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials
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To evaluate the efficacy and safety of intra-articular mesenchymal stromal cells (MSCs) injections for knee osteoarthritis (OA) treatment.
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Intra-articular MSC injection was not found to be superior to placebo in pain relief and functional improvement for patients with symptomatic knee OA. However, additional direct testing and combination trials of different type of cells, doses, and number of injections of MSCs are required to further enhance clinical decision making for people with symptomatic knee OA.
I, meta-analysis of level I studies.
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Hydrogels, which provide three-dimensional (3D) niches for encapsulating bone marrow mesenchymal stem cells (BMSCs), are becoming a promising tissue engineering solution for chondrogenic differentiation of BMSCs. However, it remains a challenge to design a hydrogel material for effective chondrogenesis of BMSCs because of the complexity of cartilage ECM and cell–matrix interactions. Thus far, various studies have shown the physical–chemical cues of hydrogel materials to impact BMSCs chondrogenesis, but the design of the 3D network microstructure of the hydrogel to induce BMSCs chondrogenesis is still far from optimized. In this study, we successfully prepared two types of collagen hydrogels, namely, the fibrous network and porous network, with the same chemical composition and similar mechanical strength but with two distinct network microstructures. The two different network microstructures significantly influenced mass transfer, protein adsorption, degradability, and contraction of the collagen hydrogels. Moreover, the cells presented distinct proliferation and morphology in the two hydrogels, which consequently modulated chondrogenic differentiation of BMSCs derived from rat. Collagen hydrogels with a fibrous network promoted more chondrogenic differentiation of BMSCs without additional growth factors in vitro and subcutaneous implantation in vivo than those with a porous network. Moreover, fibrous network resulted in less ECM calcification than porous network. However, the fibrous network could not prevent hypertrophy of the chondrogenic cells induced by BMSCs. Overall, these results revealed that the 3D network microstructure of a hydrogel was a key design parameter for the chondrogenic differentiation of BMSCs.
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Citation Excerpt :
Third, the study lacks an MSC-only group. Previous studies have shown that MSC implantation appears to repair both the articular cartilage and the subchondral bone [24–26]; thus, we omitted this group to reduce the usage of animals numbers. Fourth, regarding the limited cell number, we delivered 5 × 106 MSCs into each degenerated knee.
Both hyaluronic acid (HA) and platelet-rich plasma (PRP) injection are the common prescribed treatments for osteoarthritis (OA) patients. HA can serve as a good lubricant to reduce the fraction force of cartilage surface while PRP provide several growth factors to assist tissue repair. Considering the efficiency of tissue regeneration, mesenchymal stem cells (MSCs) injections becomes an attractive method because of their self-renewal and multi-differentiation potential. Thus, in the study, we compared the treatment effect of PRP and HA with/without MSCs. Eighteen rabbits underwent anterior cruciate ligament transection for OA knee induction, and then injected with saline, PRP, HA, HA+PRP, PRP+MSCs or HA+MSCs intraarticularly for treatment effect evaluation. Compared with the results of HA group, the cartilage treated with HA+PRP and PRP+MSCs showed better repair results in micromorphology and glycosaminoglycan synthesis. We also found that the Osteoarthritis Research Society International (OASRI) scores in HA+PRP and PRP+MSC groups were significant lower than that of the others at month 1 and month 3, separately. This indicates that the combination of HA and PRP could provide short-term tissue protection effect while PRP and MSC could provide a long-term tissue regeneration effect. PRP+MSC could be considered as a promising biological method for OA treatment.

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: Supported by the National Sports Administration of China and the Beijing Science and Technology Committee. The authors report no conflict of interest.

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Original ArticleRepair of Full-Thickness Cartilage Defects With Cells of Different Origin in a Rabbit Model

Section snippets

Methods

Macroscopic Findings

Discussion

Conclusions

Arthroscopy

Arthroscopy

Biol Blood Marrow Transplant

Bone

Articular cartilage lesions of the knee

Am J Sports Med

Arthroscopic drilling of osteochondral lesions of the knee

J Bone Joint Surg Br

Fresh osteochondral allografting of the femoral condyle

Clin Orthop

Reconstruction of articular cartilage defects with free periosteal grafts, an experimental study

Acta Orthop Scand

Rabbit articular cartilage defects treated with autologous cultured chondrocytes

Clin Orthop

Mesenchymal cell–based repair of large, full-thickness defects of articular cartilage

J Bone Joint Surg Am

Review: Tissue engineering for regeneration of articular cartilage

Biomaterials

The use of specific chondrocyte populations to modulate the properties of tissue-engineered cartilage

J Orthop Res

Regeneration of cartilage tissue by combination of canine chondrocyte and a hybrid mesh scaffold

Materials Sci Eng

Homotransplantation of carticular cartilage and isolated chondrocytes: An experimental study in rabbits

J Bone Joint Surg Br

Rabbit articular cartilage defects treated with autologous cultured chondrocytes

Clin Orthop

Original Article
Repair of Full-Thickness Cartilage Defects With Cells of Different Origin in a Rabbit Model