BIOLOGICS INJECTION THERAPY

The subject of biologics injection therapy is one of the most exciting topics in all of medicine today, and is showing the promise of ushering in a new age of treatment for curing a host of issues, from joint/sports injures (where it’s already being used regularly), to chronic diseases that up until now were thought to be incurable. This science is still in its relative infancy in the United States, in part because of FDA regulations on what can and cannot be done once the substance is harvested (more on that later). In the years that I have been exposed to biologics therapy, however, I am convinced that in the future, this is the topic that people will be talking about as being as big of a game changer as the discovery of antibiotics.

Speaking as both a physician and a patient, I’ve witnessed the effect of what a successful treatment can do for joint and soft tissue damage. It gives help to patients who had up until then resigned themselves to a life of chronic pain and/or having to consider major surgery as their only other option (and a few who had surgery with disappointing results).

In the world of sports medicine, biologics injection therapy is one of the scientific advancements that has allowed athletes to have longer, healthier careers. In the NFL alone, untold numbers of players from Chris Johnson to Prince Amukamara to Peyton Manning have undergone this treatment. Tiger Woods has been a patient for his knees. Major League baseball pitchers Los Angeles Angles pitchers Garret Richards and Andrew Heaney have opted for this treatment plan instead of undergoing the traditional Tommy John surgery to repair damaged elbow ligaments. One prominent Midwestern physician who has performed a large number of such procedures, mostly for high school and college pitchers (five of whom ended up in the major league), noted that, while he was selective about the patients he chose, only one of his patients ended up needing Tommy John surgery.

For you athletes out there, you know that your “job performance” revolves around your body working well. Your arms, legs, torso, hands, and feet are your tools as much as a drill, wrench, and saw are for a carpenter. For a pro athlete, any “tool” in his/her kit that doesn’t function well means an inability or diminished ability to work, which may mean forfeiting thousands or even millions of dollars. Most pro athletes today are well educated on the avoidance of popping anti-inflammatories and taking multiple steroid shots to stay active, having seen the toll these actions have taken on their unfortunate predecessors from previous eras. Regenerative medicine procedures such as biologics injection therapy are a major reason we’re seeing NFL players playing into their 30s, and some even into their 40s.

Biologics injections are a huge source of hope for those with chronic sports injuries, yet few subjects have had as much attention and even controversy surrounding them in the last few years.

A DEFINITION OF AND DIFFERENT SOURCES OF BIOLOGICS TREATMENT OPTIONS

Ok, a quick checklist of some of the most common substances used in biologics injections:

Autologous (i.e. coming from one’s own body) regenerative tissues are typically taken from the bone marrow or adipose (fat) cells. These have the advantage of no risk of rejection by the body, but the procedure to harvest bone marrow or fat cells is long, very expensive, and risky. Drilling a hole into bone, typically the pelvis, to get bone marrow, and making an incision in the abdomen to macerate, or “mash up” adipose cells, in effect a mini liposuction, can cause pain, bleeding, and even serious infection given the degree of bone and soft tissue penetration.

Additionally, it’s been documented that the stem cells sought in doing such procedures drop severely in number as we age. A study by AI Caplan et. al. showed that the percentage of mesenchymal stem cells, or MSCs to bone marrow cells, drops from around 1 in 10,000 at birth, to 1 in 100,000 by the teenage years, to as low as 1 in 400,000 by age 50 and 1 in 1,000,000 by age 70. While some physicians have claimed to be able to boost this number in older patients by selective exercises and a nutrition program, the concern still exists that you’re going through a long, uncomfortable ordeal without much yield to show for it.

Some of the most well-known of biologics today are those that come from the umbilical cord (the tube attached the baby’s navel that provides oxygen, food, a blood supply and waste removal up until birth). The umbilical cord contains several valuable substances that are being used at the cutting edge of regenerative medicine today:

1. Wharton’s jelly: this makes up much of the substance, or tissue, of the umbilical cord that provides most of the support around the blood supply (umbilical artery), and yes, it looks like clear jelly. This is composed of a multitude of “scaffolding” proteins (which provide an “anchor” or network for the other injected substances to stick to and not drain away), growth factors, and in some cases (depending on the preparation) live cells that can stimulate your body’s own healing factors to repair damaged tissue.

2. Umbilical cord blood: this is one of the newer biologics available, and it contains a variety of different cells, which, like the Wharton’s jelly products noted above, contain a bounty of growth factors. Additionally, the cells within the cord blood have the ability to develop in more specialized cells in line with what is needed for recovery and healing in the damaged area.

3. Exosomes: these are tiny vesicles that “bud” off from live cells, that are the newest exciting frontier in regenerative medicine. Exosomes are composed of messenger-RNA (which sends a “code” to the host’s cells to begin repair), micro-RNA (which has anti-inflammatory properties), cytokines (small proteins that act as messengers for cell-to-cell signaling that can, among other things, strengthen the immune system, carry growth factors, and provide instructions from one cell or cell to others). Because of their small size, they can cross the blood-brain barrier, and have higher concentrations of growth factors than adult stem cells.

Another treatment option (or one that can be used in conjunction with the biologics given above) consists of what is as known as placental products (i.e. from the placenta, the “birth sac” that houses and protects a developing baby, that is harvested after birth.  These products have biologic growth factors and cellular components from sources such as placental tissue that are derived from stem cells. These growth factors, much like those found in PRP (fibroblast/ epidermal/transforming growth factor,) as well as other elements are useful in tissue healing, like collagen, laminin, fibronectin, hyaluronic acid, etc. Hyaluronic acid is extremely important as the “lubricant” in the joint spaces; it’s “thick” enough to resist pressure as a shock absorber, and works with the other substances to collectively provide a strong anti-inflammatory effect (i.e. less pain). Like umbilical cord biologics products, these substances can provide excellent healing benefit.

WHEN DO YOU CONSIDER BIOLOGICS INJECTION THERAPY?

As you might guess, there’s not one easy answer for that question. Most people who come in seeking biologics injection therapy typically do so because they have joints or body parts that are severely degenerated, and they’ve usually seen several specialists after being on the typical rest/pain medication/ steroid injection/more pain medication carousel. Some of them have even tried other forms of regenerative medicine such as Prolotherapy or PRP with limited success. Others have even undergone surgery, only to find that the operation did not get rid of their pain (maybe because it didn’t target fixing the fibro-osseous junctions? Sorry, I couldn’t resist).

Another group of patients are those such as competitive or recreational athletes whose physical demands on their bodies are high and want the best option available to them. With these patients, I always do a history and physical to see if stem cell might be overkill or not in their particular case.

For example, a recreational runner with mild to moderate pain and degeneration in his patellar tendon might be just fine with a PRP injection series, but a Spartan Race or Tough Mudder competitor who trains nearly year-round (and has the joint wear and tear to prove it) might indeed be a stem cell candidate. Another patient for this second category is a gentleman in his 60s who loves alpine skiing at a high level—an activity that’s hard enough on the body when you’re younger, let alone in your seventh decade—wanting biologics injection therapy on his knees.

Age, as you might imagine, can play a factor in the decision to undergo stem cell therapy. As we mentioned in the last chapter, PRP injections can attract the body’s own local stem cells (pericytes) to help effect healing, but these diminish in quantity as we age – chronic inflammation to a joint can, and will, wear them out. The other issue is the joint being treated – some joints (e.g. hips) tend to need a more robust treatment plan than other joints that on average tend to heal faster and better.

My “typical” biologics injection patient is either a younger person who has suffered a severe injury and has not fully recovered to return to his or her sport of choice despite a lengthy rehab process, or a middle-aged adult with chronic, nagging joint injuries (statistically, low backs and knees are the most common), that they’ve thrown everything and the kitchen sink at to fix to no avail. Physical therapy, massage, steroid injections, rhizotomy (elective burning of joint nerve ending), acupuncture—nothing worked.

While there are some patients who are not, medically speaking, good candidates for this treatment, I have been amazed at the improvement that this treatment plan can provide in pain reduction and increase in function in what at first glance seems like a “hopeless” case.

IS BIOLOGICS INJECTION THERAPY FOR EVERYBODY?

To be sure, there are patients that I feel would not benefit from this therapy, and there are some conditions under which it should not be performed (e.g., active or recently active cancer, chronic infection). But if a patient knows the odds, has no absolute contraindications to treatment, and is willing to follow the protocol, as a rule they should be given a chance. I personally have no interest in cherry picking only the “best” or “ideal” candidates for regenerative medicine treatment in order to skew the data to make it look like I get the highest percentage of patients with excellent improvement. That looks good in an advertisement, but it means that by doing so you are likely excluding people for whom you may be their last hope of getting out of life-altering pain. For a man or woman with chronic low back pain they rate as an 8/10 in severity (i.e., so bad you don’t want to move and it’s hard to focus on anything besides the pain), a treatment that may lower your pain level to 4/10 can feel just shy of miraculous.

One patient of mine who was suffering from chronic pain in his feet put it this way: “You’re the quarterback of your team in the championship game, you’re down by 4 points with 6 seconds left to play, and you’re 30 yards from the end zone. The opponent’s defensive end is about to sack you, but your receiver running towards the end zone isn’t clear of his defender. Do you throw the ball in the hope your receiver will make the grab, or take the sack and lose for sure?” One of my sports idols,

“His Airness” Michael Jordan, put it slightly differently:

“You miss 100% of the shots you don’t take.”

SOME EXAMPLES OF BIOLOGICS INJECTION THERAPY OUTCOMES

CASE #1 – BIOLOGICS INJECTION THERAPY FOR HIP PAIN

Brenda was a woman in her mid-50s who suffered from severe left hip pain, which had gotten worse with inactivity and the weight gain that resulted from it. She was using a cane to help her ambulate and stated that she had pain with every step. She did not want to have a total hip replacement, and did not want to be stuck on a regimen of heavy-duty pain medications for the rest of her life. What impressed me about her was her willingness to do what was physically necessary to avoid surgery and limit her pain if stem cell therapy could help her somewhat.

On examination, she had the typical signs of bad pain from osteoarthritis: pain radiating to her groin, pain with weight bearing on her affected (left) leg, a very limited range of motion, and a flare up of discomfort when her leg was internally rotated. Her X-ray, not surprisingly, looked awful. Where a normal hip shows a “ball and socket” configuration with the head of the femur (ball) and the acetabulum (socket), Brenda’s joint looked like a ball that had smashed into its socket doing 90 mph.

There was bony growth all around the head of the femur and the acetabulum, and no joint space between the two to speak of. In truth, this was one of those cases where I was second-guessing myself as to whether or not I did the right thing by attempting this procedure instead of recommending her to an orthopedic surgeon.

Brenda received an injection of 2 milliliters of cellular Wharton’s jelly with 1 milliliter of amniotic tissue under ultrasound guidance into her hip and the surrounding support ligaments. Six weeks later she came back, per our protocol, for a PRP injection to provide additional growth factors. After a period of rest, she began a gentle home exercise program and physical therapy. When I saw her a few weeks later, she reported with a smile that the majority of her pain was gone. She still had a slight limp, but was ambulating without a cane, and while her hip range of motion remained limited, there was no pain when it reached its end range, even when I applied extra pressure.

I actually spoke to Brenda just prior to the release of this book to see how she was feeling. She noted that her hip pain was “nowhere near what it was before” and as a result of her increased ability to ambulate and exercise had lost 75 lbs. since I last saw her in clinic!

Brenda also followed up with me not long ago (about 2 ½ years after her injections) to tell me that her hip pain is a 0/10, and she no longer uses her cane. Now, whenever I have a case that I’m on the fence about for doing biologics injection therapy with a patient who fully understands the risk that it may not work, I think of Brenda and what biologics injection therapy has done for her.

CASE #2 – BIOLOGICS INJECTION THERAPY FOR KNEE PAIN

Nick was an 88-year-old gentleman with a long history of right knee pain and degenerative arthritis. He had a history of having fractured his right patella (kneecap) twice, once in childhood and once when in the army, and in his own words, the X-ray of his patellofemoral compartment of his knee (one of the three knee compartments, which consists of the patella and the area between it and the femur) looked like a dog had chewed on it. Despite the obvious degeneration on his right knee in all compartments, he was an amazingly active gentleman with very few complaints of pain and was in excellent health.

Nick had received Prolotherapy, PRP, and even PRP with placental tissue  to his right knee in the past several times with only limited success. He remained optimistic, however, kept a good weight and active lifestyle for his age, and after explaining the option of stem cell therapy to him he agreed to the procedure. Nick received 2 milliliters of cellular Wharton’s Jelly and 1 milliliter of placental tissue into his knee and surrounding structures. As he lived out of town, contact with him regarding his knee was limited and he was not able to make it back in for the PRP “booster” injection I typically do. When I evaluated him for a separate musculoskeletal condition some months later, however, I asked him if he would like me to treat his right knee as well in the same procedure; his response was that his knee no longer gave him any trouble, and he had not thought about the joint for some time.

Nick’s case is a great example of how you never judge a book by its cover—just because a patient is elderly doesn’t disqualify them for stem cell therapy. You need to look at a host of other factors—their weight, diet, overall health, fitness, degree of pathology in the area to be treated, etc.— before telling the patient your best estimate on improving their quality of life. In Nick’s case, both his advanced age and joint arthritis were secondary to his remarkable vigor for an 80-something who had done all the right things with his health prior to his procedure. Without this therapy, his life would have been that much more difficult with the discomfort his knee was giving him.

BIOLOGICS INJECTION THERAPY AND THE FUTURE

In summary, there is a promising tomorrow for research and therapy on this subject. There are reports of its use outside the US for treating spinal cord injury patients, some of whom are regaining motor function in their limbs they thought were forever gone, and even for degenerative nervous system diseases such as ALS (aka Lou Gehrig’s Disease) that have shown real promise of providing hope in an otherwise hopeless condition.

The future is truly bright for many people suffering from chronic disease with the advent of biologics procedures… and we’ve just scratched the surface.