Mesenchymal Stem Cell Therapy in the Sports Knee

Abstract Background:

The relationship between biological tissue healing following knee injury or surgery and long-term clinical outcome has come to the forefront of sports medicine practice. This has led many knee surgeons to incorporate biologically mediated healing factors into the management of knee injuries. In particular, the clinical use of mesenchymal stem cells has opened new horizons.

Relevant studies were identified through a search of PubMed from January 2000 to April 2011, combining the term mesenchymal stem cells with articular cartilage, anterior cruciate ligament, and meniscus. Relevant citations from the reference lists of selected studies were also reviewed.

Knee injury treatment with mesenchymal stem cells shows potential. Most reports represent animal model studies; few advances have been translated to human clinical applications.

Mesenchymal stem cell use to promote healing following knee injury is likely to increase. There are scientific methodological concerns and ethical and legal issues regarding mesenchymal stem cell use for treating knee injuries.

Keywords: biological tissue healing, cell-based therapy, cartilage repair

Many patients who have sustained knee injuries desire treatment options that will enable them to continue sports participation. Over the past several years, the sports medicine community has seen an increase in the use of biological agents, including cell-based therapies for this purpose.78 The introduction of stem cells, specifically mesenchymal stem cells (MSCs), into the clinical setting has opened new knee treatment horizons ().12

Mesenchymal stem cell (MSC) harvest, isolation, and culturing. Clinical studies have been performed with MSC injections under a periosteal patch or in combination with a scaffold to treat articular cartilage defects. Intra-articular MSC injections have ...

Stem cells harvested from human embryos and adult tissues have the capacity for self-renewal.52,76 The utility of adult stem cells is generally restricted to the generation of more of the same tissue from which it was harvested, such as hematopoetic stem cells in blood.9 However, under certain conditions, some adult stem cells, such as those harvested from mesenchymal tissues, can differentiate into multilineages and become multipotent. MSCs are characterised by surface-specific antigen and the absence of hematopoetic stem cell markers, such as leukocyte common antigen.15Friedenstein et al26 demonstrated that bone marrow cells could differentiate into bone and cartilage. Subsequent research found that MSCs harvested from bone marrow could differentiate into bone, cartilage, tendon, ligament, fat, and other tissues of mesenchymal origin.42,68 MSCs can also be harvested from synovium,16,18 periosteum,27 skeletal muscle,1 adipose tissue,21,89,96 trabecular bone,71 and umbilical cord blood.54

One of the primary concerns in articular cartilage repair is the integration of engineered calcified articular cartilage with underlying bone. MSC-mediated chondrogenesis may improve this integration.42-48,93 Since Ashton et al5 first reported MSC-mediated chondrogenesis, others have investigated chondrogenic potential when derived from tissues as diverse as human adipose19 and trabecular bone,71 as well as rat bone marrow, synovium, periosteum, adipose, and muscle tissues.11,94 Bone marrowderived MSCs may allow better differentiation of the deep calcified articular cartilage zone adjacent to healthy bone.23,62,80 MSCs harvested from bone marrow have been the primary source in most animal model and human chondrogenesis research studies.13,14,33 MSCs derived from rat synovium may have greater proliferation and chondrogenesis potential than rat bone marrow, periosteum, adipose, or muscle sources. In humans, bone marrow has a high MSC density, providing similar culture expansion potential compared with other tissue sources.61,72,94 A rabbit study by Koga et al47 reported that MSCs harvested from bone marrow and synovium had a greater potential to repair articular cartilage defects than cells from skeletal muscle and adipose tissue.37

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Mesenchymal Stem Cell Therapy in the Sports Knee