STEM CELL THERAPY
Use of stem cell therapy is based on the properties of the proliferation and differentiation of multipoint MSC lines. These stem cells can theoretically regenerate injured tissues and influence repair through immunomodulation; paracrine activity through the release of bioactive agents, such as cytokines, trophic, and chemotactic molecules; and cell differentiation into various cell lineages.15,16,13,17 Orthopedic surgeons have used microfracture to recruit MSCs during cartilage repair procedures for over 20 years. This procedure draws multipotent MSCs to the injured site to induce chondrogenic proliferation and fibrocartilage repair.28
Adult MSCs provide a readily accessible autologous source of stem cells for regenerative therapies. MSCs can be isolated from a variety of tissues, including bone marrow, adipose tissues, synovia, human umbilical cord blood, and peripheral blood. The majority of stem cell therapies in the United States for sports medicine purposes are conducted using bone marrow aspirate concentrate (BMAC) and adipose tissues. The US Food and Drug Administration (FDA) allows the use of minimally manipulated autologous stem cells to be injected into the same patient on the same day. However, some studies reported that culturing stem cells or introducing products, such as collagenase to stem cells, can increase the stem cell concentration prior to injection. These processes constitute more than “minimal manipulation” and therefore would require drug trials prior to use in the United States.
Although MSCs can be readily obtained from a variety of tissue sources, the makeup of the cell concentrate differs. Bone marrow and adipose tissues are readily available sources of homogenous MSCs. Harvesting stem cells from adipose tissues provides a less invasive route of collection than from BMAC. Harvested BMAC and adipose tissues consist of heterogeneous cell populations that are composed of precursor and accessory cells, such as pericytes, endothelial cells, smooth muscle cells, fibroblasts, and macrophages in addition to MSCs.
Animal studies reported promising results when evaluating soft tissue lesions in small and large animal models.14,15 Although clinical and human evidence remains limited, the potential of MSCs for regenerative repair has led to a recent increase in the number of related clinical studies. Multiple systematic reviews have concluded that MSC therapy is safe for the treatment of osteoarthritis, cartilage lesions, and tendinopathies. Limited evidence is available regarding the safety of intramuscular use, and a theoretical concern arises on the development of heterotopic bone formation as a result of treatment.13,16 The efficacy of MSC therapy is difficult to determine due to the lack of standardization in stem cell populations, adjuvants (eg, PRP, hyaluronic acid, and scaffolding preparations), and delivery methods used.13,17
Similar to PRP, the increased use of MSC therapy among high-profile athletes has led to the promotion of these therapies as safe and effective despite limited evidence.29 Although MSC therapy is a promising and safe treatment option for patients with soft tissue injuries, the paucity in data and human studies limit its clinical use. Moreover, data of MSC efficacy is complicated because of the disparity between clinical studies regarding MSC collection method (many of which eclipse the “minimal manipulation” standard), description of isolated cell concentrates, dosage, method of delivery, use of adjuvants, and lack of randomization. Further studies using [standardized] methods are needed before establishing a true consensus on the safety and efficacy of MSC therapy.
AMNIOTIC MEMBRANE
The placenta is a source of MSCs, a collagen-rich extracellular matrix, and bioactive growth and regulatory factors. The capacity of the placenta to modulate biological activities and tissue formation is thought to provide a means of tissue repair and healing. The placenta consists of amniotic fluid, amniotic membrane (AM), chorionic membrane, and umbilical cord blood and tissues. Although MSCs have been isolated from each component of placental tissues, amniotic and chorionic membranes and umbilical cord tissues yield the highest concentration.
The majority of regenerative studies involving the placenta used AM alone or in combination with other placental tissues. AM is a metabolically active tissue that consists of an epithelial layer, a basement membrane, and a mesenchymal tissue layer. In addition to being a source of stem cells, AM synthesizes many growth factors, vasoactive peptides, and cytokines, which are capable of tissue regeneration. AM was initially used as a biological scaffold for the treatment of skin burns and wounds. Other intrinsic properties of AM include the provision of a matrix for cellular migration and proliferation, enhanced wound healing with reduced scar formation, antibacterial activity, and lastly, non-immunogenic and immunosuppressive properties. These inherent characteristics have spurred studies on the potential use of AM in sports medicine as a minimally invasive means to treat osteoarthritis and injuries of tendons, ligaments, muscles, fascia, and cartilages.
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