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0.5% had local tissue reactions. Companion Animals In 2007, this technology was made available to small animal veterinarians for dogs and cats, with more than 1000 cases of connective tissue and joint repair reported through 2009,9 and a greater than 80% success rate in blinded, placebo-controlled canine clinical trials.10 Recently in-office stem cell procedure kits have become available, allowing for treatment at the clinic or on the farm, depending on the species of animal receiving therapy. STEM CELL CHARACTERISTICS There are 2 kinds of stem cells: • Embryonic (prenatal) stem cells • Adult (postnatal) stem cells.11 Although most lay people recognize the term embryonic stem cells, the important potentials of adult stem cells have been recognized in the veterinary and human medical literature since 1963, when Becker, et al, reported on the regenerative nature of bone marrow.12 Embryonic Stem Cells Embryonic stem cells are, in theory, able to transform into any type of tissue; they are totipotent when an egg is fertilized; then after several divisions are pluripotent. 13 Although less of an issue in veterinary than human medicine, there are religious, political, and ethical issues that limit the use of fetal stem cells. Adult Stem Cells Postnatal adult stem cells: • Retain regenerative or reparative capabilities as undifferentiated cells • Maintain homeostasis in all tissues MSC Proliferation Commitment Lineage Progression Differentiation Maturation Osteogenesis Transitory Osteoblast Osteoblast Osteocyte BONE Chondrogenesis Transitory Chondrocyte Chondrocyte Hypertroph Chondrocyte CARTILAGE Myogenesis Myoblast Myoblast Fusion Myotube MUSCLE Tendogenesis Ligamentagenesis Transitory Fibroblast T/L Fibroblast TENDON/ T LIGAMENT Other Adipocytes and Other Cells ADIPOSE TISSUE Evidence growing: Skin, Nerve and Organ Tissue PLURIPOTENT (?) DIFFERENTIATION OF THE ADIPOSE-DERIVED MESENCHYMAL STEM CELL (AD-MSC) Figure 1. Flow chart elucidating possible commitment, lineage progression, and maturation of adipose-derived mesenchymal stem cells Defining Potency • Totipotency is the ability of a single cell to divide and produce all the differentiated cells in an organism, including extraembryonic tissues. • Pluripotency refers to a stem cell that has the potential to differentiate into any of the 3 germ layers: 1. Endoderm (interior stomach lining, gastrointestinal tract, lungs) 2. Mesoderm (muscle, bone, blood, urogenital) 3. Ectoderm (epidermal tissues, nervous system). • Multipotency refers to cells that retain the capability to differentiate into a variety of cellular phenotypes derived from 1 germ layer. • Are capable of repair or regeneration in a tissue or organ system. These multipotent cells are locally activated to proliferate and differentiate into some, or all, of the major specialized cell types of tissue when required for maintenance or repair. They facilitate tissue maintenance, regeneration, growth, and wound healing throughout life with the capability of differentiation to a wide variety of types of adult cells, such as muscle, bone, cartilage, tendon-ligament, and adipose tissues.14 Adult stem cells are found in all tissues in the body15 in varying quantities, with major reservoirs in adipose tissue16 and, to a lesser extent, bone marrow.17 Both bone marrow and adipose tissue are derived from embryonic mesodermal tissues and contain a microvascular network, including extracellular matrix and extensive perivascular stroma, which is credited for clinical promise in regenerative medicine applications.18 Adipose-Derived Adult Stem Cells Adipose stroma contains large numbers of undifferentiated stem/stromal cells capable of producing all tissue types derived from the mesodermal layer.19,20 These AD-SCs have the potential to differentiate to tenoligamentous, skeletal muscle, smooth muscle, and cardiac muscle.21,22 AD-SCs also have the potential to differentiate into tissue derived from ectodermal and endodermal origins, such as organ tissue, nerves, and skin, suggesting that they have pluripotent and multipotent capabilities (see Figure 1).23-32 Recent studies have determined the safety and efficacy of implanted/administered AD-SCs in various animal models as well as human clinical trials. AD-SCs also meet certain criteria described for the ideal stem cell for regenerative medicinal applications:33,34 • Found in abundant quantities • Harvested with a minimally invasive procedure • Can be differentiated along multiple cell lineage pathways in a regulatable and reproducible manner • Can be safely and effectively transplanted. As a result, adipose tissue has become an important resource for research and patient care applications in human and veterinary medicine. HIGH-DENSITY PLATELET-RICH PLASMA CONCENTRATES Enhanced healing capability is possible when platelet concentrations are increased within injured or damaged tissue.35 Platelet-rich plasma has been used successfully as a treatment modality in both veterinary (equine) and human medicine. High-density platelet-rich plasma (HDPRP)is defined as plasma with platelet concentrations > 4 times the levels found in circulating blood. It is isolated and concentrated from a peripheral venous blood sample by bidirectional centrifugation.36 Various portable commercial centrifugation units exist forin-office use; however, there