Y’all know what I love? Open access science, that’s what. And that’s why this week’s good news about cell therapy comes from an article that’s freely available to every single one of you, right here on the regular old internet. This study actually came out about a year ago, but I think it deserves a little more attention than it’s received thus far. Here’s why: this study executed a head to head comparison of hyaluronic acid (HA) injections (aka viscosupplementation) and platelet rich plasma (PRP), which is frequently a topic of conversation with doctor and patients. The authors concluded that PRP achieved longer lasting results in all patients and was more effective in reducing pain and disability (as measure by a quality of life scale) in patients with less severe arthritis.

Arthritis Is Mechanical and Biological

Before we explore the cool facets of this study, I’d like to remind everyone of the nature of the beast in osteoarthritis. I recently gave a talk about the multi-faceted nature of arthritis progression, and I made a very “this came from a scientist” graphic for it. The graphic was pulled from several different reviews on OA implicated biochemical pathways and factors, but I think it highlights the hot mess (that’s a scientific term) of players involved in OA progression.

000 051217 A NEW PARADIGM

So we have a LOT of interacting factors here, and the hilarious (frustrating) part is that no one really knows which comes first – the mechanical or the biochemical. Of course there are some examples like trauma where we’re fairly certain one preceded the other, but the majority of cases still pose the question of the chicken or the egg. Regardless of what comes first, we know that inflammation is at the center of this process. The presence of TNF and interleukins is implicated in more publications than we can count, and those proteins play into almost every aspect of OA progression. As you can see in the diagram, inflammation contributes to changes in chondrocyte behavior, encouraging them to chew up more extracellular matrix than they produce, and also causing them to literally malfunction and die. Cell death contributes to the purple box in the bottom left as well as the top middle ALARMINS box, where mechanical elements are shown to have biochemical effects which encourage further progression of OA. Inflammation also plays into decreased mitochondrial activity, robbing cells of their power source and impairing their ability to generate extracellular matrix. It (inflammation) also decreases cells’ ability to regulate their metabolism in response to stressors and their cellular mechanism for taking out malfunctioning organelle trash. The main thing to glean from this is that mechanical damage leads to positive biochemical feedback loops, and biochemical factors like inflammation lead to positive mechanical *and* biochemical feedback loops. So if we as a scientific community want to really address this disease, we probably need to look at interventions capable of disrupting multiple parts of this web of OA progression.

Hyaluronic Acid Addresses Mechanical Components of OA Progression

For patients reading this post, let me quickly clarify what HA is and how it functions when applied to OA. In the preceding paragraph, I mentioned extracellular matrix (ECM) a lot. ECM is the highly viscous goo produced by cartilage cells in our joints. It provides structural and biochemical (nutritional) support to the cells around it. In a joint, ECM is part of what keeps a joint moving and able to absorb impact. When the cascade of changes discussed above start happening, cells start making poor quality ECM, or none at all if they’ve died, increasing the likelihood of further mechanical damage due to impaired lubrication and shock absorption. HA injections were supposed to be a way to address this poor ECM issue by infusing a large dose of high quality ECM proteins, and there is evidence that it can alter the mechanical aspect of OA and possibly some of the biochemical factors as well. HA has been shown to decrease the activity of ECM destroying proteins (read this!) and suppress their production as well as decreasing pain in knee OA patients (read this!). The thing we have to remember is that HA is a fairly inert substance as compared to the rest of the players in the OA game. So even though it has some positive effects, it’ll never be as powerful as something that alters the behavior of cells in the joint, or powerfully disrupts one of these positive feedback loops.

Platelet Rich Plasma Out-Performs Hyaluronic Acid in Knee OA

Finally, the point of this post: these researches in Spain compared a series of HA injections to a series of platelet rich plasma injections for knee OA. The idea with PRP is to boost the positive growth factors in the area, thereby providing the local cells with active biological agents capable of altering several of those feedback loops I keep mentioning. Patients were assessed at three and six months post-treatment, and their pain, quality of life, and knee outcome scores were compared. The authors concluded that the two treatment options yielded similar improvements overall, but PRP seemed to have an earlier effect as well as an overall better effect in patients in the earlier stages of OA. Now, it’s worth noting that the PRP used in this study was special. First, it was leukocyte and RBC depleted, second, and most impossible to execute here in the US, it was prepped at the first visit, frozen, and held for use in the second and third injections. The study points out that this was a quality control measure, whereby each PRP injection would be standardized. Unfortunately, that’s not something we can do in the US. I think it’s overall more important that they depleted the RBCs and WBCs, because commercial systems here in the US are fairly capable of generating consistent PRP preps from a single patient. If I had to speculate, I’d say that the natural, already found in the human body and tasked every day with inducing healing, components of PRP were responsible for the accelerated results found in the PRP treatment group. I don’t necessarily think this is the pinnacle of what we can do with cells in OA, but the results are encouraging.

My favorite takeaway from this study is the subtle insinuation that PRP be combined with HA for an even more effective intervention. Based upon these clinical results, and the chutes and ladders style path leading to the black hole of osteoarthritis progression, I’m pretty stoked about the possibility of combining these two treatments. So I hope some of y’all are working on that now, and if you are, I hope you’ll let us know in the comments!

Today’s good news about cell therapy: platelet rich plasma (a cell based therapy) provided superior results vs hyaluronic acid in knee osteoarthritis!