Concise Review: The Clinical Application of Mesenchymal Stem Cells for Musculoskeletal Regeneration: Current Status and Perspectives

Abstract

Regenerative therapies in the musculoskeletal system are based on the suitable application of cells, biomaterials, and/or factors. For an effective approach, numerous aspects have to be taken into consideration, including age, disease, target tissue, and several environmental factors. Significant research efforts have been undertaken in the last decade to develop specific cell-based therapies, and in particular adult multipotent mesenchymal stem cells hold great promise for such regenerative strategies. Clinical translation of such therapies, however, remains a work in progress. In the clinical arena, autologous cells have been harvested, processed, and readministered according to protocols distinct for the target application. As outlined in this review, such applications range from simple single-step approaches, such as direct injection of unprocessed or concentrated blood or bone marrow aspirates, to fabrication of engineered constructs by seeding of natural or synthetic scaffolds with cells, which were released from autologous tissues and propagated under good manufacturing practice conditions (for example, autologous chondrocyte implantation). However, only relatively few of these cell-based approaches have entered the clinic, and none of these treatments has become a "standard of care" treatment for an orthopaedic disease to date. The multifaceted reasons for the current status from the medical, research, and regulatory perspectives are discussed here. In summary, this review presents the scientific background, current state, and implications of clinical mesenchymal stem cell application in the musculoskeletal system and provides perspectives for future developments. STEM CELLS TRANSLATIONAL MEDICINE 2012;1:237-247

Mesenchymal stem cells derived from vertebrae (vMSCs) show best biological properties

“…Preclinical and clinical results show that, independently from the method used to deliver MSCs into the musculoskeletal system, the direct application of these cells on a loss of bone substance stimulates bone regeneration [4]. Recently, FernandezBances et al [18] treated seven patients with pseudoarthrosis of a long bone through introduction of MSCs derived from iliac crest bone marrow of the same patient supported by allogenic cancellous bone graft (from the local bone bank), obtaining consolidation in all the cases.…”

“…They can be isolated from different tissues, grown ex vivo, and induced to differentiate in vitro into multiple cell types, including bone, cartilage, fat and stroma [3]. Considering this ability MSCs have been used clinically for several regenerative approaches in the musculoskeletal system, using different methods for cell harvesting from a donor site and cell delivery to the musculoskeletal system [4]. MSCs can be derived from blood by venous puncture or derived from bone marrow by, for example, aspiration from iliac crest or by surgical removal from a donor site, with increasing levels of invasiveness.…”

Biological Augmentation and Tissue Engineering Approaches in Meniscus Surgery

“…Although further work on point-of-care strategies such as BMAC is required, it may be that the next generation of genetically manipulated MSCs may further enhance the regenerative process by promoting growth factor production and directed cell differentiation. 80,81 As another cell type for discussion, synoviocytes have often been overlooked in meniscus regeneration and repair augmentation. 82 This is despite the fact that meniscus repair has been shown to be facilitated by fibroblasts from the surrounding synovium and joint capsule that are believed to undergo fibrocartilaginous metaplasia at the repair site.…”

Adenosine production: a common path for mesenchymal stem-cell and regulatory T-cell-mediated immunosuppression

“…Achieved results in each of such conditions are not the scope of this review and may be revised elsewhere [125][126][127][128][129][130].…”