STEM CELL THERAPY

The subject of stem cell 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. Stem cell therapy is still in its relative infancy in the United States, in part because of FDA regulations on what can and cannot be done once stem cells are harvested (more on that later). In the short time I have been exposed to stem cell injection therapy, however, I am convinced that, years from now, 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 stem cell therapy 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, stem cell 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.1 Tiger Woods has been a stem cell patient for his aging 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 stem cell 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.

If you want to see just a sampling of professional athletes that have undergone this treatment, this website illustrates 38 such athletes who have had stem cell treatments: [https://bioinformant.com/athletes-stem-cell- treatments].

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 stem cell therapy are a major reason we’re seeing NFL players playing into their 30s, and some even into their 40s.

Stem cells 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 STEM CELLS/ STEM CELL PRODUCTS

Ok, a quick Biology 101 lesson on stem cells first:

Stem cells are undifferentiated, or “ground zero,” cells that haven’t received the proper biochemical signals to form specific tissues in the body. If you recall high school Biology, as we develop from a ball of cells after fertilization, every cell in our body has the same DNA and potential to form practically any organ or tissue needed. But with time and the release of hormones’ direction, growth, and differentiation, certain genes are switched on and most others are permanently turned off.

If you take, say, a chicken embryo in an early stage of development, pluck a cell in what will form the brain and place it in the area were the quadriceps (thigh) muscle will grow, that cell will develop into a muscle cell instead of a neuron. As a result of this ability to adapt, stem cells are also called “pluripotent,” because they are capable of giving rise to a multitude of different tissue types.

The source of most of the controversy over stem cells comes from embryonic stem cell harvesting. But these stem cells are not the kind of stem cells I (or any physician I know) use, for obvious legal and ethical reasons. The two sources of stem cells I am aware of that are available to people in the United States for musculoskeletal injuries are autologous stem cells (cells derived from the patient’s own body) and allogeneic stem cells (cells derived from a donor to be transplanted into a patient).

Autologous stem cells are typically harvested from a person’s own bone marrow or adipose (fat) cells. Allogeneic stem cells are typically harvested from sources such as the human placenta, umbilical tissue, or in some cases, umbilical cord blood, all of which are collected and prepared right after birth from donor mothers, and pose no risk to either mother or child.

A third treatment option is what is as known as “stem cell product” or “tissue allografts.” These are biologic growth factors and cellular components from sources such as placental tissue that are derived from stem cells. Some of these products contain no live stem cells, and others may or may not have viable stem cells once the cells are thawed after deep freezing. These growth factors, much like those found in PRP (fibroblast/ epidermal/transforming growth factor,) as well as other elements are useful in tissue healing (collagen, laminin, fibronectin, hyaluronic acid, etc.). Tissue banks that produce these products typically don’t make a claim to providing live stem cells, but will stand by the healing benefit these tissue allografts can provide.

STEM CELL OPTIONS

The discussion on which stem cell/stem cell product source is the best has produced as many opinions as who the greatest rock band of all time was. Each option has its pros and cons.

Autologous stem cells have the advantage of no risk of rejection or other adverse immune reaction, 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 stem cell counts drop severely 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 to 10,000 at birth, to 1 to 100,000 by the teenage years, to as low as 1 to 400,000 by age 50. 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.

In other countries, this can be worked around by incubating a person’s MSCs for a few days to increase their number and then re-injecting them into the desired area of the body. In the United States, however, this procedure is currently illegal, as the Federal Drug Administration (FDA) has a requirement that only “minimal manipulation” is allowed with stem cells and products, and that treatments must be begun and concluded on the same visit.

As the use of stem cell therapy is an emerging science that we are learning more about every few months, you’ll find that there is no “standard” stem cell therapy treatment protocol from one regenerative medicine physician to the next. Different experts work with what their experience and/or the experience of those they have learned from has told them gives the best outcome. As such, most practitioners (like myself) have seen an evolution in the way they perform their procedures.

For example, there are doctors who will simply inject allogeneic stem cells alone and see how the patient does in the follow-up visits over the ensuing weeks to months. Other doctors will do a follow-up PRP booster injection four to six weeks later. From what I’ve learned (my experience plus the experience of those whom I’ve learned from) I find it more efficacious to inject stem cells, either allogeneic or autologous (i.e., outside source or from the patient’s own body) with PRP at the initial injection. Then I do a PRP booster around six weeks later, as stem cells require both the growth factors present in abundance in PRP and the effect of PRP to further aid the healing process by drawing the patient’s own local stem cells that still exist to the damaged area.

For some conditions, stem cell product/tissue allograft is a useful fit, and I have seen good to excellent results with this. As with any treatment plan, you have to take it on a case-by-case basis and look at multiple factors to see what the most reasonable approach for the patient is given their circumstances (physiological, financial, even emotional). The key to being a good medical provider for MSK/sports injuries is being flexible. Different patients have different needs depending on their injuries and situations in life. Beware the “one-size-fits-all” clinics out there.

WHEN DO YOU CONSIDER STEM CELL INJECTIONS?

As you might guess, there’s not one easy answer for that question. Most people who come in seeking stem cell therapy typically do so because they have joints or body parts that are severely degenerated, and they’ve usually seen several specialists and been on the typical rest/pain medication/ steroid injection/more pain medication merry-go-round. Some of them have even tried other forms of regenerative medicine such as Prolotherapy or PRP with limited success. Some 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 stem cell 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 attract local stem cells (pericytes) to help effect healing, but these are in lower abundance as we age. The other issue is the joint being treated.

My “typical” stem cell 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 stem cell therapy can provide in pain reduction and increase in function in what at first glance seems like a “hopeless” case.

IS STEM CELL THERAPY FOR EVERYBODY?

To be sure, there are patients that I feel would not benefit from stem cell therapy, and there are some conditions under which stem cell therapy 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 game 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 nerve 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 STEM CELL THERAPY OUTCOMES

CASE #1 – STEM CELL 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 mesenchymal stem cells derived from umbilical cord 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! Now, whenever I have a case that I’m on the fence about for doing stem cell therapy with a patient who fully understands the risk that it may not work, I think of Brenda and what stem cell therapy has done for her.

Given the amount of pathology in her hip, it’s unlikely that this lady will ever have a perfect, completely painless hip joint, but going from debilitating pain and considering joint replacement to mild/minimal pain, being able to walk better, participate in therapy, and lose weight by being more active (all of which in themselves will lessen pain on a weight bearing joint like the hip) is in itself amazing when you consider her starting point.

CASE #2 – STEM CELL 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 graft matrix (the growth factors found in placental tissue often used in regenerative medicine) 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 2cc’s of mesenchymal stem cells derived from umbilical cord tissue and 1cc of umbilical cord tissue, also known as Wharton’s Jelly, 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 stem cell therapy, his life would have been that much more difficult with the discomfort his knee was giving him.

CASE #3 – STEM CELL THERAPY FOR HIP PAIN

You probably have guessed that I’d share another one of my war stories, right? Here’s my stem cell therapy success:

Sometime in early 2017, I began to get a gradually worsening pain in my right hip, particularly along the inner thigh area, that began to spread to my lateral hip and even my right buttock/pelvis. At the time, I was driving around like a madman to our different clinics scattered around the state of South Carolina, sometimes going to a different clinic every day of the work week and logging over 3,000 miles a month. We had a sedan/sportscar with a low seat that kept my hips flexed and close to my body for hours a day driving. I’m sure that this, combined with lack of exercise and weight gain, were catalysts to the problem. Eventually the pain got so bad that I was waking up two to three times a night to adjust the pillow between my legs (without which sustained sleep was impossible), and when I either swung my right leg in front of/across my body to the horizontal position, or had to get up from a deep-seated position, an extremely painful “click” could be heard and a painful release sensation.

As you might guess from how I handled my back situation in the last chapter, I kept pushing through until finally, in early 2018, I decided to try PRP injections on myself. I did a total of three rounds of PRP in and around my hip, including self-administered ultrasound guided injections in the joint. I held the ultrasound probe in my left hand, a PRP syringe and 3 ½” needle in the right, trying to avoid the major blood vessels and femoral nerve. And just to be safe, I had my wife on speed dial in case I screwed up. This helped to a moderate degree. I had slightly less pain at night and along my lateral hip, but that awful catch-and-release sensation persisted. This injury was also affecting my ability to stretch the right side of my back, which tightened up and began to hurt due to my inability to extend my right leg across my body to twist my torso.

When I finally relented and completed my MRI, my fears were realized: I had sustained damage to the medial (side near the pelvis) aspect of the labrum, the cartilage that surrounds the hip joint and allows for smooth articulation of the joint. I believe “shredded” was the term the radiologist used in his report. Oy.

When I attended a conference in May of 2018, I had ordered two milliliters of MSCs to my hotel, and an experienced colleague of mine kindly consented to inject me, using PRP to reconstitute the cells. He did a very comprehensive injection in and around the hip, and included the right pelvis. Despite the fact that we were out of anesthetic to numb me up first, I got through it fine (although I won’t deny it smarted a bit). Seven or eight weeks later, I did a self-administered PRP booster injection of my hip (but not my pelvis—I don’t inject what I can’t see!). In both cases, the post- injection soreness/inflammatory phase was short-lived, maybe two days, and very tolerable. I was able to go about my normal business without the need for pain medications.

At the time I am writing this chapter, I am a little over nine months since my initial stem cell treatment, and my hip is easily 75–80% improved. The catching/snapping sensation is much less common and typically mild, and I can finally bring my right leg across my body without the awful aching/ stabbing feeling. I no longer wake up at night from the hip pain and don’t need the pillow between my knees. Two weeks ago, I went on the first long run I’ve done in nearly a year, with no pain in my hip or pelvis that night or the next few days (although my cardiovascular fitness left something to be desired).

STEM CELL THERAPY INJECTIONS AND THE FUTURE

In summary, there is a promising tomorrow for stem cell research and therapy. 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 stem cell procedures, and we’ve just scratched the surface.