A Comprehensive Review of Stem-Cell Therapy

» Regenerative orthopaedics has been used as a biological alternative to conventional therapy and surgical intervention for treating musculoskeletal conditions associated with limited therapeutic options.

» Orthopaedic investigators have shown promising early clinical results by developing cell-based approaches to regenerate injured cartilage, tendon, ligaments, and bone.

» Despite continued research, issues regarding harvesting, delivery of treatment, cost, indications, and optimal timing of intervention must be considered.

» Multidisciplinary networks of investigators are essential to achieve the full clinical and therapeutic potential of mesenchymal stem cells in orthopaedics.

» Although mesenchymal stem cells offer great promise for the treatment of degenerative diseases and orthopaedic conditions, there is still a dearth of properly conducted controlled clinical studies.

In 1998, a team of researchers led by James Thomson reported their successful creation of the first human embryonic stem cells. Their research ushered in a new era for drug discovery and transplantation medicine. In the past few decades, molecular genetics has progressed from the laboratory to the clinic in the hopes of finding new applications.

The use of developmental biology focused on translational research has helped to shape the field of regenerative medicine. Rapid advances in tissue engineering and cellular therapies have caused a paradigm shift from pharmacological treatment to the construction of biological substitutes that can regenerate diseased organs or injured tissues.

In orthopaedics, conventional strategies for treating several musculoskeletal conditions, such as osteoarthritis, still remain ineffective. Orthopaedic investigators have begun investigating cellbased techniques to develop novel therapeutic agents to address biological solutions for orthopaedic conditions. Orthopaedic injuries that are treated with operative intervention may not heal as intended and complete function may not be regained. As a result, there has been increasing focus on understanding the pathophysiology of orthopaedic disease processes in order to develop regenerative interventions for clinical use.

Regenerative orthopaedics was first recognized in 1965 with the discovery of the osteoinductive properties of bone morphogenetic proteins (BMPs)4-6. However, the use of BMPs has proven not to be as dramatically effective in clinical practice as was once hoped. Several studies have even highlighted the substantial clinically adverse effects of their use7-9. Considering the potentially harmful and economically expensive implications of BMP applications, the orthopaedic community turned research interests toward identifying cell-based approaches to regenerating the musculoskeletal system.

One of the most promising cellular sources is mesenchymal stem cells (MSCs). MSCs hold great potential for the treatment of musculoskeletal conditions, and several recent advances in the field have shown promise.

The purpose of the present comprehensive review is to provide an overview of stem cell research in orthopaedics while addressing the potential clinical applications as well as challenges of this therapy.