Data Availability StatementNot applicable. presence of growth factors, cytokines, hyaluronic acid, and extracellular vesicles. Results All samples passed the sterility test. Growth factors including IGFBP 1, 2, 3, 4, and 6, TGF-, and PDGF-AA were detected. Several immunomodulatory cytokines, such as RANTES, IL-6R, and IL-16, were also detected. Pro-inflammatory cytokines MCSFR, MIP-1a; anti-inflammatory cytokines TNF-RI, TNF-RII, and IL-1RA; and homeostatic cytokines TIMP-1 and TIMP-2 were observed. Cytokines associated with wound healing, ICAM-1, G-CSF, GDF-15, and regenerative properties, GH, were also expressed. High concentrations of hyaluronic acid were observed. Particles in the extracellular vesicle size range were also detected and were enclosed by the membrane, indicative of true extracellular vesicles. Conclusion There are numerous growth factors, cytokines, hyaluronic acid, and extracellular vesicles present in the Whartons jelly formulation analyzed. The amount of these factors in Whartons jelly is higher compared with other biologics and may play a role in reducing inflammation and pain and augment healing of musculoskeletal injuries. strong class=”kwd-title” Keywords: Regenerative medicine, Musculoskeletal injuries, Osteoarthritis, Biologics, Umbilical cord, Whartons jelly, Growth factors, cytokines, Hyaluronic acid, Exosomes Background Ligament, muscle, and tendon injuries produce pain, loss of function, instability, and secondary osteoarthritis [1, KU-55933 inhibitor database 2]. Traditionally, these injuries have been managed using activity modification; physical therapy; pharmacological agents, such as non-steroidal anti-inflammatory drugs, corticosteroids, viscosupplementation, and narcotics; and surgical procedures when conservative management fails . These modalities have limitations and potential side effects . Over the last KU-55933 inhibitor database decade, there has been an increased interest in the use of biologics for regenerative medicine applications . Biologics currently used in clinical practice include platelet-rich plasma, bone marrow aspirate, adipose tissue aspirate, amniotic fluid, amniotic membrane, umbilical cord-derived Whartons jelly and cord blood [6, 7]. The healing capabilities of these products are attributed to the presence of stem cells, growth factors, cytokines, hyaluronic acid, and/or extracellular vesicles including KU-55933 inhibitor database exosomes . Stem cells, including mesenchymal stem cells isolated from bone marrow, periosteum, adipose tissue, trabecular bone, and deciduous teeth, have produced marked interest for their applications to regenerative medicine . Stem cells are able to differentiate along specific lineage in response to signal transduction mediated by growth factors and cytokines . Growth factors and cytokines often have overlapping activities. They are able to target mesenchymal, endothelial, and epithelial cells, and can act in an autocrine or paracrine manner . In addition, one cytokine can stimulate the synthesis and release of other cytokines leading to a network of interacting molecules. This complex network of cytokines and growth factors can guide cell division, differentiation, and regeneration of different tissues and organs . Hyaluronic acid, a polysaccharide found in most tissues, is a major component of extracellular matrix of the skin, joints, and eyes . Hyaluronic acid has been used to manage knee osteoarthritis via its chondroprotection, proteoglycan and glycosaminoglycan synthesis, and anti-inflammatory, Rabbit polyclonal to CCNB1 mechanical, subchondral, and analgesic actions . Exosomes are small extracellular vesicles with diameter ranging from ~?30 to 150?nm, developed from a sequential process of multivesicular body membrane remodeling . Exosomes are found in multiple body fluids including blood plasma, amniotic fluid, and Whartons jelly [12, 13]. Exosomes are secreted from several cell types including stem cells and represent an important mode of intercellular communications . Recently, exosomes have also emerged as an attractive KU-55933 inhibitor database cell-free therapeutic alternative that holds great regenerative potential . The increasing applications of biologic therapies for regenerative medicine have led to considerable marketing, patient demand, and clinical utilization . To be compliant in the United States (U.S.), biologics that adhere to the U.S. Food and Drug Administration (FDA) regulation of human cells, tissues, and cellular and tissue-based products (HCT/Ps) regulated under title 21, part 1271 of the Code of Federal.