Accumulating evidence indicates that multipotent cells derived from bone marrow, fat, bone, muscle, and other tissues exhibit significantly different properties, identities, and differentiation potential,11,12 but in many cases are referred to as MSCs

Accumulating evidence indicates that multipotent cells derived from bone marrow, fat, bone, muscle, and other tissues exhibit significantly different properties, identities, and differentiation potential,11,12 but in many cases are referred to as MSCs.13,14 Beyond basic science research, the translational applications of stem cells in orthopaedics has focused primarily on cell therapy or tissue engineering, with more recent expansion into the development of microphysiologic systems and disease modeling. development and/or regeneration of mesenchymally-derived tissues.1 However, in recent years, the name MSC has led to significant controversy and debate.6,7 It can be argued that MSCs meet the two fundamental requirements of a stem cell (i.e., self-renewal and ability for differentiation).8 However, it remains to be identified if this definition is PLA2G3 met broadly has been limited by the techniques available to track and evaluate function of MSCs following implantation. Further misunderstandings has arisen from the recognition of related but unique populations of multipotent cells, likely of perivascular source, in tissues such as adipose cells, muscle, tendon, bone, and synovium, but with combined and inconsistent terminology being utilized to describe them. Accumulating evidence shows that multipotent cells derived from bone marrow, fat, bone, muscle, and additional tissues exhibit significantly different properties, identities, and differentiation potential,11,12 but in many instances are referred to as MSCs.13,14 Beyond fundamental science study, the translational applications of stem cells in orthopaedics offers focused primarily on cell therapy or cells engineering, with more recent expansion into the development of microphysiologic systems and disease modeling. Cell therapy indicates the intro of isolated cells without a structural scaffold, usually through injection into the target site (e.g., intra-articularly or intra-discally), or in some cases, intravenously. Cells executive offers generally focused on combining cells, biomaterial scaffolds, and environmental factors (e.g., growth factors, bioreactors) to regenerate cells Evocalcet replacements for implantation. Despite incredible progress in these areas, however, there have been few long-term successes in the translation of stem cell therapies to medical therapies.15,16 Preclinical studies for tissue-engineered repair of cartilage and bone have been quite encouraging, but most clinical procedures either lack regulates or have shown long-term results that are equivocal to standard-of-care.17,18 Similarly, stem cell therapies have shown significant promise in controlled preclinical animal studies,19C21 but have not demonstrated consistent clinical effectiveness in prospective and randomized Evocalcet tests.22C24 Despite the lack of clear evidence to support these stem cell therapies, numerous clinics continue to offer unproven methods in the United States, with an unknown quantity of such clinics outside the United States giving various cell therapies as medical tourism. Not only do many of these procedures not involve actual stem cells, there have been a number of severe adverse effects that have been recorded due to unproven stem cell therapies,25 including growth of a mucus-producing nose in the spine,26 tumor formation,27 blindness,28 and illness.29 Indeed, the results of less than half of stem cell clinical trials are published, suggesting that many negative findings in the stem cell field go unreported.30 Furthermore, many of these clinics are misusing the term stem cell or cellular therapy to treat various musculoskeletal conditions. The United States Food and Drug Administration (FDA) defines a somatic cell therapy as the Evocalcet administration to humans of autologous, allogeneic, or xenogeneic living cells that have been processed (FDA Guidance for Market). This definition is important as many of these clinics claim bone marrow aspirate concentrate (BMAC) like a stem cell therapy, with limited medical data to support this notion. BMAC is becoming more popular in the medical community to treat musculoskeletal accidental injuries and diseases due to the limited regulatory barrier for medical use – bone marrow aspirate is definitely.