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Biologics

The use of biologic agents in the alleviation of back pain

Introduction

Low back pain results from a cascade of events occurring at the cellular level within the intervertebral disc and facet joints. Due to their limited blood supply the intervertebral disc and the facet joints have a limited capacity to restore their structural integrity once damage has occurred. Over the last 5 years there has been a great deal of interest in the use of biological agents derived from blood(Mohammed and Yu, 2018), bone marrow(Pettine et al., 2016) and subcutaneous fat tissue(Comella et al., 2017) in the treatment of low back pain. Of these therapies, the use of fat tissue appears to contain the largest quantity of reparative (stem-cell like) cells that are able to promote healing within degenerative tissue(Bosetti et al., 2016). These cells are able to self-renew with a high growth rate and possess the ability to develop into cells and structures akin to those in which they are implanted(Bosetti et al., 2016).

Platelet-rich plasma

Platelet Rich Plasma(PRP) has been in clinical use for the management of musculoskeletal conditions for several years(Mlynarek, 2016). It is defined as autologous blood with platelet concentrations above physiological baseline. Because PRP is derived from the patients’ own blood it carries very few side effects with low risks of infection and allergic reaction(Nagae et al., 2007). It is postulated that PRP promotes endogenous healing processes. It is believed that PRP stimulates the recruitment, proliferation of cells central to regeneration via a number of growth factors and proteins released from platelets(Anitua et al., 2005, Sys et al., 2011). Over the last 24 months there has been an explosion in robust evidence indicating that intradiscal PRP injections are effective in successfully alleviating symptoms associated with disc degeneration(Levi et al., 2016, Akeda et al., 2017, Comella et al., 2017). Indeed, in the first double-blind randomised controlled trial(RCT) of intradiscal PRP injection participants demonstrated significant improvement in outcome scores for function, pain and quality of life for a sustained period of at least 1 year(Tuakli-Wosornu, 2016).

Bone Marrow derived mesenchymal stem cells

Bone marrow is a rich store of the bodies own source of mesenchymal stem cells(MSC). MSCs are stem cells that have extensive proliferative capacity(Elabd et al., 2016). In addition to their incredible ability to differentiate into various cellular subtypes depending on their host environment bone marrow derived MSCs(bMSC) possess profound immunomodulatory properties that promote cellular repair and homeostasis(Pourgholaminejad, 2016, Chen et al., 2016). Trials have demonstrated that biologic therapy using bMSCs is effective in decreasing pain, improving function and halting structural deterioration in patients with back pain(Pettine et al., 2016, Noriega et al., 2017, Orozco et al., 2011).  The effect of these treatments is long lasting, with over 80% of patients managing to avoid a surgical intervention at 24-months(Pettine et al., 2016). In addition to symptomatic relief follow-up MRI imaging at 12 months has demonstrated that bMSC intradiscal injections halt disc degeneration(Pettine et al., 2016). This compelling evidence highlights the potential role of bMSC intradiscal injections in managing low back pain.

Fat derived mesenchymal like stem cells

The bodies fat stores is a rich reservoir of previously unknown MSCs. These adipose derived MSCs(aMSC) are considerably easier to harvest than bone marrow derived MSCs. Using established methods such as the Lipogems device(Bianchi et al., 2013), these cells can be harvested without the need for complex culturing techniques(Bosetti et al., 2016). Additionally, the concentration of MSCs derived from adipose tissue has been demonstrated to be higher than that derived from bone marrow(Murphy et al., 2013). Adipose derived MSCs have also been demonstrated to be more potent immunomodulators when compared to bMSC(Melief et al., 2013). Results from recently published clinical trials examining the role of intradiscal aMSC injections have demonstrated that patients report significant improvement in pain, function and quality of life scores(Kumar et al., 2017, Comella et al., 2017). These improvements occurred in conjunction with increased discal water content at 12 months following cellular transplantation with aMSCs(Kumar et al., 2017).  Indeed no cases were observed to have worsening radiographic imaging over the course of the trial following biologic therapy(Kumar et al., 2017). The ubiquity of aMSC and the established uncomplicated harvesting methods means that we are likely to see a vast increase in the use of such therapy in the management of low back pain.

References

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