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As an autologous treatment, platelet   alone. A follow-up MRI study show no   preparations (AFPs) found no MSCs,
        and growth factor concentration can   regenerative benefit in the BMAC treated   various growth factors and hyaluronan
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        be quite variable depending on patient   knees. 26,27  Bone marrow can be harvested   were present in all AFPs.  A multicenter
        specific factors and the preparation   reliably from various sites in the body   prospective RCT comparing amnion
        system utilized. PRP preparations can   including the posterior and anterior iliac   suspension allograft (ASA) to HA and
        either be leukocyte rich (LR-PRP)    crests, distal femur, proximal tibia, and   saline demonstrated lower pain and
        or leukocyte poor (LP-PRP). LR-PRP   distal humerus; although the posterior   improved clinical outcome scores in
        (includes white blood cells) is thought   iliac crest appears to yield the highest   patients treated with a single ASA
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        to induce an inflammatory response,   concentration of MSCs. 3,19,22  Overall,   injection at 6 months follow-up.  Further
        while LP-PRP (lacking white blood cells)   BMAC is more invasive and expensive   data is needed to support the use of
        is largely considered anti-inflammatory.   than PRP with increased harvest   amnion in osteoarthritis, but early results
        For the treatment of OA, there is high-  morbidity. Future work would need to   are promising.
        level data supporting the efficacy of   demonstrate clear superiority in the non-
        LP-PRP, particularly in mild to moderate   operative treatment of early osteoarthritis   Summary and Future Directions
        osteoarthritis, while LR-PRP has been   to justify expanded utilization.   Non-operative interventions are first-line
        shown to be more efficacious in the     Similar to BMAC, adipose-derived   treatments for early knee osteoarthritis.
        treatment of tendinopathies. 15,24  While   stem cell (ASC) preparations are   Patient specific regimens include weight
        LP-PRP has good evidence to support its   another cell-based therapy aimed at   loss, activity modification, core-to-floor
        use in the treatment of symptomatic OA,   harvesting autologous MSCs. Adipose   rehabilitation, and the use of bracing
        it is often not covered by insurance plans   cells are harvested percutaneously and   and/or assist device. Medications and
        and therefore can be a prohibitive out-  mechanical processing removes lipids   biologic injections are utilized as adjuncts
        of-pocket expense for the patient despite   and disrupts adipose tissue clusters while   to reduce pain and inflammation so that
        proven efficacy. 18                  maintaining the stromal vascular fraction   patients may rehabilitate successfully.
           Other orthobiologic injection options   that is rich in ASCs. ASC therapies focus   Short and long acting corticosteroid and
        are cellular products often improperly   on isolating ASCs from adipose tissue,   high molecular weight IA-HA produced
        referred to as “stem cell” therapies. These   similar to BMAC and amnion. In vitro   by bacterial fermentation will likely have
        include autologous bone marrow aspirate   studies have shown that there are 300   a continued role in the treatment of early
        concentrate (BMAC) and adipose-derived   times more MSCs in adipose tissue than   knee osteoarthritis.
        MSCs, and allogeneic amnion injections.   in BMAC for the same sample size.  The   Orthobiologic injections have a growing
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        These therapies work by concentrating   current literature on ASCs is limited by   place in the management of early knee
        MSCs within the above FDA limitations of   short-term follow-up, limited numbers,   osteoarthritis. These injections reduce
        minimal manipulation and homologous   and inadequate reporting of preparation   symptoms but may also modulate the
        use. Again, MSCs are not stem cells   protocols used and composition of   joint environment to promote knee
        but are signaling cells that, when   formulation. 9,14,23  This is a promising area   homeostasis. There is good data to support
        activated, respond to their surrounding   of future research given the richness   the use of LP-PRP for symptomatic early
        microenvironment by homing in on a site   of MSCs within adipose and relative   knee OA. Preliminary data also supports
        of injury, secreting regenerative, anti-  ease of harvest. Cost concerns and   the safety and efficacy of cellular based
        inflammatory and immunomodulatory    insurance approval are limiting factors   products (i.e., autologous BMAC and
        factors, and recruiting and stimulating   to widespread clinical application in the   adipose, allogeneic amnion). Regulatory
        the resident stem cells to repair and   near future.                      issues, cost concerns, and insurance
                                5
        regenerate the injured tissue.          Finally, amniotic-derived treatments   approval limit the widespread clinical use
           BMAC is harvested from red bone   have been used in medicine for the   of orthobiologics for early osteoarthritis.
        marrow. In addition to MSCs, this    treatment of various ailments for over   Future high level studies are required.
        contains growth factors associated with   a century; although research regarding   We must establish safe, optimized, and
        suppression of inflammatory cytokines,   their use in orthopaedics has only   standardized preparations so that we
        chondrocyte proliferation, and stem cell   recently begun.  These amnion-derived   know exactly what we are injecting into
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        migration and differentiation.  BMAC   products obtained from the placenta   our patients. Only in this manner can
                                7,29
        is often used to aid in bone healing and   after cesarean delivery are screened,   we ensure safety and maximize efficacy.
        bony integration,  but there is a only a   washed, and processed. There are   Most importantly, we must all practice
                      4
        low level of evidence available to support   various processing methods, resulting in   evidence-based medicine, advocate for
        its primary use in osteoarthritis. A   cellular and acellular preparations, both   and educate our patients, and remain
        recent RCT showed that BMAC is safe   of which contain vital proteins, growth   fiscally responsible. The future of
        and improves pain in knee OA patients,   factors, and extracellular matrix.  While   orthobiologics relies on an ethical and
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        but was not superior to saline injection   a recent study on several amniotic fluid   scientifically rigorous approach.


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