Biologic Adjuvants for the Management of Osteochondral Lesions of the Talus

MaCalus V. Hogan, MD, MBA; Justin J. Hicks, MD; Monique C. Chambers, MD, MSL; John G. Kennedy, MD, FRCS

Disclosures

J Am Acad Orthop Surg. 2019;27(3):e105-e111. 

In This Article

Stem Cells

Embryonic Derived Mesenchymal Cells

Embryonic-derived mesenchymal cells (EMCs) are pluripotent stem cells with the ability to differentiate into all three primary germ layers: endoderm (eg, lining of the gastrointestinal tract and lungs), mesoderm (eg, muscle, bone, cartilage, blood), and ectoderm (eg, nervous tissue).[24] This pluripotency and unlimited self-renewal distinguishes EMCs from adult stem cells, which have limited differentiating ability and are considered multipotent. The utilization of EMCs for cartilage repair is in its infancy. Currently, very few studies have been conducted to evaluate the ability of EMCs to repair osteochondral defects. EMC have been induced in vitro to form MSCs including chondrocytes.[25,26] Pilichi et al[24] demonstrated that delivery of EMCs into osteochondral defects in sheep femoral condyles improved cartilage regeneration for up to 24 months. Cheng et al[27] used EMCs encapsulated in a fibrin gel and implanted these cells into patellar groove osteochondral defects. The authors observed improved histologic scoring and upregulation of chondrogenic genes in groups receiving EMCs. Although promising, the use of EMC-derived chondrocytes for the clinical management of cartilage defects is far off. Further research is needed to characterize their potential to repair damaged cartilage. In addition, the use of EMCs raises ethical concerns because they are derived from the early-stage preimplantation embryo. Furthermore, their ability to self-renew and multilineage properties raise concern regarding tumorigenicity.

Bone Marrow-derived Stem Cells and Bone Marrow Aspirate Concentrate

MSCs are adult stem cells that can be found in bone marrow and other tissues. These stem cells are multipotent with the ability to differentiate along connective tissue cell lineages, including chondrocytes, osteoblasts, and myocytes. MSCs are thought to be responsible for physiologic growth, wound healing, and replenishing cells lost during daily cell turnover and have been shown to be effective for managing musculoskeletal tissue injury. Bone marrow stem cells are the most commonly used source of cells for cartilage regeneration. They are an optimal option for cartilage regeneration because they are widely available and can be accessed easily during surgery from the patient's iliac crest among other locations. Derived from adult tissue, MSCs also avoid the ethical concerns associated with EMCs. Concentrated bone marrow aspirate (cBMA) is a source of MSCs and is a potential biologic adjunct to OLT treatment modalities. In addition to MSCs, cBMA also contains platelets that contain growth factors within the platelet α-granules, analogous to PRP (Table 1). These growth factors may potentially augment the regenerative and reparative capacity of MSCs. Another major advantage of cBMA is that it can be obtained and prepared during the index procedure.

Evidence supporting bone marrow aspirate as an adjunct to cartilage repair has been demonstrated in preclinical animal models (Figures 1 and 2). In an equine model, Fortier et al[28] compared microfracture alone with microfracture with cBMA to manage full-thickness cartilage defects of the lateral trochlear ridge. Histological and MRI analysis indicated improved healing in the cBMA group. Early studies suggest that these findings have translated to surgical repair of human OLTs. Improved clinical outcome scores and radiographic findings have been demonstrated in several clinical studies (Table 3). These findings may be limited by defect size as Kim et al found that large lesions (>109 mm2) and subchondral cysts predicted unsatisfactory outcomes. Additional long-term randomized controlled trials are needed. Reporting of defect size and depth is critical to understanding the efficacy of bone marrow stem cell as an adjunct to OLT repair and will aid in the optimization of this method.

Figure 1.

Magnetic resonance imaging (MRI) of the osteochondral lesion of the talus (OLT). A, Coronal T2 showing medial talar dome OLT with surrounding marrow edema. B, Sagittal T1 image showing medial central dome OLT with findings consistent with unstable fragment.

Figure 2.

Osteochondral lesion of the talus (OLT) repair with iliac-crest bone marrow aspirate concentrate (BMAC). A, OLT during initial insertion of BMAC, B, insertion of prepared BMAC injection. C, OLT with BMAC in place after microfracture and débridement. D, OLT following final placement of BMAC and Tisseell.

Adipose-derived Stem Cells

Adipose tissue represents another source of MSCs capable of differentiating into chondrocytes. In vitro, cartilage derived from adipose stem cells has a high total collagen count but lower levels of type II collagen. A recent study by Kim et al[33] comparing marrow stimulation in OLT with marrow stimulation augmented with adipose stem cells demonstrated improved clinical and MRI outcomes scores in the adipose stem cell group compared with marrow stimulation alone. Although encouraging, the self-renewal capacity of adipose stem cells is not completely understood, and further studies are needed to optimize the chondrogenic potential of these cells.

Synovial- and Periosteum-derived Stem Cells

Synovial chondromatosis, a benign tumor of the synovial membrane, led researchers to investigate the cartilage regeneration potential of these cells. In vitro, chondrocytes derived from the synovial lineage retain fibroblastic characteristics needed to form hyaline cartilage. Studies comparing them with MSCs demonstrate higher chondrocyte differentiation potential.[34] Application of synovial stem cells to OLT surgery is far from clinical application; however, their potential for future use is intriguing.

Another novel source of stem cells is periosteum-derived cells. Periosteum-derived cells have the potential to serve as chondroprogenitor cells and are currently appreciated for their dual lineage (bone and hyaline cartilage) potential. Further studies are needed to characterize conditions to induce cartilage growth.[25]

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