Regenerative medicine in the context of musculoskeletal injury is a broad term that offers potential therapeutic solutions to restore or repair damaged tissue. The current focus in recent literature and clinical practice has been on cell based therapy. In particular, much attention has been centered on autologous bone marrow concentrate (BMAC) and adipose-derived (AD) mesenchymal stem cells (MSCs) for cartilage and tendon disorders. This article provides an overview of MSC-derived therapy and offers a comprehensive review of adipose- and bone marrow-derived MSC therapy in primary knee osteoarthritis OA. LEVEL OF EVIDENCE: To be determined.

Autologous biologics, defined as platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMC), are cell-based therapy treatment options in regenerative medicine practices, and have been increasingly used in orthopedics, sports medicine, and spinal disorders. These biological products are produced at point-of-care; thereby, avoiding expensive and cumbersome culturing and expansion techniques. Numerous commercial PRP and BMC systems are available but reports and knowledge of bio-cellular formulations produced by these systems are limited. This limited information hinders evaluating clinical and research outcomes and thus making conclusions about their biological effectiveness. Some of their important cellular and protein properties have not been characterized, which is critical for understanding the mechanisms of actions involved in tissue regenerative processes. The presence and role of red blood cells (RBCs) in any biologic has not been addressed extensively. Furthermore, some of the pathophysiological effects and phenomena related to RBCs have not been studied. A lack of a complete understanding of all of the biological components and their functional consequences hampers the development of clinical standards for any biological preparation. This paper aims to review the clinical implications and pathophysiological effects of RBCs in PRP and BMC; emphasizes hemolysis, eryptosis, and the release of macrophage inhibitory factor; and explains several effects on the microenvironment, such as inflammation, oxidative stress, vasoconstriction, and impaired cell metabolism.

III.

Background: In vivo amniotic fluid is known to contain a population of mesenchymal stem cells (MSCs) and growth factors and has been shown to assist in healing when used as an adjunct in procedures across multiple medical specialties. It is unclear whether amniotic fluid products (AFPs) contain MSCs and, if so, whether the cells remain viable after processing. Purpose: To determine whether MSCs, growth factors, and hyaluronan are present in commercially available AFPs. Study Design: Descriptive laboratory study. Methods: Seven commercial companies that provide amniotic fluid were invited to participate in the study; 3 companies (the manufacturers of PalinGen, FloGraft, and Genesis AFPs) agreed to participate and donated AFPs for analysis. The AFPs were evaluated for the presence of MSCs, various growth factors relevant to orthopaedics (platelet-derived growth factor ββ, vascular endothelial growth factor, interleukin 8, bone morphogenetic protein 2, transforming growth factor β1), and hyaluronan by enzyme-linked immunosorbent assay and culture of fibroblast colony-forming units. These products were compared with unprocessed amniotic fluid and 2 separate samples of MSCs derived from human bone marrow aspirates. All groups used the same culture medium and expansion techniques. Identical testing and analysis procedures were used for all samples. Results: MSCs could not be identified in the commercial AFPs or the unprocessed amniotic fluid. MSCs could be cultured from the bone marrow aspirates. Nucleated cells were found in 2 products (PalinGen and FloGraft), but most of these cells were dead. The few living cells did not exhibit established characteristics of MSCs. Growth factors and hyaluronan were present in all groups at varying levels. Conclusion: The AFPs studied should not be considered “stem cell” therapies, and researchers should use caution when evaluating commercial claims that products contain stem cells. Given their growth factor content, however, AFPs may still represent a promising tool for orthopaedic treatment. Clinical Relevance: Amniotic fluid has been proposed as an allogenic means for introducing MSCs. This study was unable to confirm that commercial AFPs contain MSCs.

Autologously prepared bone marrow aspirate concentrates, have the potential to play an adjunctive role in various patient pathologies that have not been able to heal with conventional treatment modalities. The use of bone marrow aspirate (BMA) and concentrates in regenerative medicine treatment plans and clinical applications is based on the fact that bone marrow cells, including progenitor and nucleated cells, platelets, and other cytokines, support in tissue healing and tissue regenerative processes. The use of concentrated BMA cells focuses primarily on mesenchymal stem cells (MSCs), with the ability to self-renew and differentiate into multiple cell types. Concentrated bone marrow cells can be retrieved from harvested BMA and ensuing minimal manipulative cell processing techniques, executed at point of care (POC). The application of bone marrow biological therapies may offer solutions in musculoskeletal pathologies, spinal disorders, chronic wound care, and critical limb ischemia (CLI), to effectively change the local microenvironment to support in tissue healing and facilitate tissue regeneration. This chapter will address the cellular content of bone marrow tissue, harvesting and preparation techniques, and discuss the biological characteristics of individual marrow cells, their inter-connectivity, and deliberate on the effects of BMA concentration.