Mesenchymal stem cells in the treatment of traumatic articular cartilage defects: a comprehensive review

Abstract

Articular cartilage has a limited capacity to repair following injury. Early intervention is required to prevent progression of focal traumatic chondral and osteochondral defects to advanced cartilage degeneration and osteoarthritis. Novel cell-based tissue engineering techniques have been proposed with the goal of resurfacing defects with bioengineered tissue that recapitulates the properties of hyaline cartilage and integrates into native tissue. Transplantation of mesenchymal stem cells (MSCs) is a promising strategy given the high proliferative capacity of MSCs and their potential to differentiate into cartilage-producing cells - chondrocytes. MSCs are historically harvested through bone marrow aspiration, which does not require invasive surgical intervention or cartilage extraction from other sites as required by other cell-based strategies. Biomaterial matrices are commonly used in conjunction with MSCs to aid cell delivery and support chondrogenic differentiation, functional extracellular matrix formation and three-dimensional tissue development. A number of specific transplantation protocols have successfully resurfaced articular cartilage in animals and humans to date. In the clinical literature, MSC-seeded scaffolds have filled a majority of defects with integrated hyaline-like cartilage repair tissue based on arthroscopic, histologic and imaging assessment. Positive functional outcomes have been reported at 12 to 48 months post-implantation, but future work is required to assess long-term outcomes with respect to other treatment modalities. Despite relatively positive outcomes, further investigation is required to establish a consensus on techniques for treatment of chondral and osteochondral defects with respect to cell source, isolation and expansion, implantation density, in vitro precultivation, and scaffold composition. This will allow for further optimization of MSC proliferation, chondrogenic differentiation, bioengineered cartilage integration, and clinical outcome.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-014-0432-1) contains supplementary material, which is available to authorized users.

Optimal Seeding Densities for In Vitro Chondrogenesis of Two- and Three-Dimensional-Isolated and -Expanded Bone Marrow-Derived Mesenchymal Stromal Stem Cells Within a Porous Collagen Scaffold

“…1 BMSCs seeded within biomaterial scaffolds and implanted into focal chondral defects are capable of resurfacing cartilage in animal and human joints, although inconsistent outcomes have been reported based on macroscopic assessment, histological analysis, magnetic resonance imaging, and clinical scoring. [2][3][4][5][6][7] Repair tissue quality has been shown to correlate with functional outcome. [6][7][8] Therefore, tissue-engineering variables, such as cell expansion environment and seeding density of scaffolds, are currently under investigation with the goal of improving neocartilage quality.…”

Outcomes of cartilage repair techniques for chondral injury in the hip—a systematic review

“…However, these cells were recently proven to have the ability to differentiate into a different tissue in response to specific signals released by the site of injury, including cartilage injury [51,52]. Adding to animal studies, several authors reported on intra-articular injection of MSCs into the knee for the treatment of cartilage defects and showed good results with regard to pain and clinical outcomes [53][54][55][56]. Injected MSCs were incorporated into the articular cartilage of the injected joint.…”

Chondrogenic Differentiation of Human Chondrocytes and Stem Cells in Different Cell Culture Systems Using IGF-1-Coupled Particles

“…In addition, using IGF-1-coupled particles to induce chondrogenic differentiation of BM-MSCs, glycosaminoglycan synthesis was significantly enhanced, compared to BM-MSCs cultured with a single application of soluble IGF-1. The growth factor IGF-1 is known to increase the proliferative capacity of MSCs and also to enhance the synthesis of extracellular matrix proteins [7,15]. The use of particles as a carrier and delivery system seems to improve prolonged availability of IGF-1 within the scaffold, resulting in superior proteoglycan synthesis compared to single application of soluble IGF-1.…”