When stem cell therapy works and does not work for your knee pain

Ross Hauser, MD

Why stem cell therapy did not or will not work for your knee pain

If you are reading this article it is very likely that you are exploring stem cell therapy for your degenerative knee condition or for the knee problems or surgical recommendations of knee replacement for a loved one. Either you or your loved one is in a lot of pain now and maybe right now is not the right time to get a knee replacement.

When opting for regenerative medicine injections, providers and the patients have to have a realistic idea of just how effective or non-effective these treatments can be. For some patients stem cell injections can be of great benefit in helping prevent or delay the need, long-term, for knee replacement surgery. For others, stem cell therapy results will be disappointing and non-effective. So how do you know?

An explanatory note: In this article, we will refer to our published research. In this research, we cite case histories with our patients who had a type of stem cell therapy. This treatment is called “Whole Bone Marrow Aspirate.” It is the stem cells from aspirated bone marrow.

Not every patient needs stem cell therapy

At our center, while we do offer this treatment, it is rare that we will use it. We feel based on more than 28 years of experience that we can achieve similar if not better and more stable results using Prolotherapy (dextrose injections) and varying strength Platelet Rich Plasma injections. This is explained in the video below, when do we use stem cell therapy, PRP, or Prolotherapy injections.

We explain more about the different types of knee injections that may help you in our very extensive article What are the different types of knee injections for bone on bone knee.

In the image below direct bone marrow Prolotherapy

The caption below reads: Procedure for direct bone marrow Prolotherapy. Whole bone marrow is utilized the Prolotherapy procedure because it contains the healing elements in the stem-cell niche and stromal fraction.

1. Procaine or other suitable numbing agent is injected into the tibia to anesthetize the site of the bone marrow extraction.
2. An EZIO drill is used to pierce the tibial bone for extraction of the bone marrow.
3. The bone marrow is drawn from the tibial bone.
4. The entire bone marrow aspirate is then injected directly into the knee joint or other injury site.
5. Following the bone marrow treatment standard Prolotherapy is performed around the entire joint to accelerate the growth and repair of the surrounding ligaments and tendons. Steps 4 and 5 are interchangeable.

Realistic assessments of a good candidate and bad candidate for stem cell therapy

When stem cell therapy will likely not help you.  Perhaps the number one reason that stem cell therapy will not help your knee pain is if you have no remaining range of motion. If your knee is fused, cannot bend, is stuck in a bent in or bent out position, and held in place by bone spurs and osteoarthritic boney overgrowth. If you have some range of motion, if you can walk with aid, can manage to get yourself in and out of a chair or car, and can walk steps, a consultation would be in order to further assess the success and amount of success this treatment may have for you.

From an email: It has been edited for clarity.

“I am a 56 year-old active woman. I suffer primarily with osteoarthritis in my right knee. Former runner, sustained torn meniscus in 2010 and had partial meniscectomy. Re-injured knee doing a run in 2012. RICE helped some, was able to jog for a couple years, even did a full marathon on all flat asphalt later in 2012. Knee pain gradually worsened, tried cortisone injections, helped some. Second set of cortisone injections six months later helped but not as much. Had a few sets of Euflexxa between 2015-2018. Helped initially then as time progressed, less effective. Had arthroscopy in 2018. Had stem cell therapy summer of 2020. Did nothing.  I was told efficacy or procedure wasn’t guaranteed, about 50/50 at best. Had Durolane injections, helped a little. Pain getting worse with age, can walk a 15 minute mile but getting more difficult and slowing down. Feeling very down and hopeless. Feel too young for knee replacement but maybe it’s time.”

Video: What type of treatment do I need? Is Stem Cell Therapy one of them?

In this video, Danielle R. Steilen-Matias, MMS, PA-C, offers a brief introduction to treatments. Explanatory and summary notes are below on the types of patients we see.

Prolotherapy? Platelet Rich Plasma Therapy? Stem Cell Therapy? This is among the most common questions that we get.

A major factor in determining which treatment to get is the extent of your injury and whether this is a recent injury or a problem with degenerative joint disease or degenerative arthritis.

General patient type 1: Younger patient, athlete, active, or with a physically demanding job. Recent injury, such as a sprain that has not healed all the way.

• Injury is still causing pain and discomfort.
• This is the type of injury that does very well with dextrose Prolotherapy injections.
• Dextrose is sugar water that when injected into the injured joint attracts your own healing repair cells into the area to fix damaged soft tissue such as ligaments and tendons.

General patient type 2: Chronic problems from an “old” injury, such as a sprain that happened a few years ago. The injury “never really healed” has progressively worsened. Causing pain, discomfort.

• Injury has not responded long-term to more conservative care options such as NSAIDs, medications, cortisone, physical therapy
• Soft tissue damage continues, joint instability has become more permanent.
• In this patient, it may not be enough to attract your own cells to this damaged area with Prolotherapy, in this type of case we may have to put cells there, by injection. Our first option would be Platelet Rich Plasma Therapy (PRP). This would put the healing factors found in your blood platelets into the damaged joint.
• WE DO NOT offer PRP as a stand-alone treatment or injection. While PRP brings healing cells into the joint, it acts to repair degenerative damage. In our experience, while PRP addresses damage deep in the joint, we must still address the joint instability problem created around the joint. We do this with Prolotherapy. Here damaged or weakened ligaments that are simply “stretched,” can be strengthened with treatment to help restore and maintain normal joint mobility.
• Simple PRP on the inside, Prolotherapy on the outside of the joint.

General patient type 3: Chronic long-term degenerative problems. Possibly in need of a joint replacement

• This is a patient who may have had degenerative joint disease for many years even decades. These are the “bone on bone people.” They have exhausted all means of conservative care, they may have had short-term success with PRP treatments, hyaluronic acid treatments, cortisone injections, but none of these are helpful anymore.
• It is important to realize and it will be explained in this article, that it is rare that we would need to go to stem cell therapy in many of these patients. When we do recommend stem cells it would be from your own stem cell sources and mostly taken from bone marrow. We do not offer “stem cell therapy,” from the donated source material.

Sometimes a patient will reach out to us and suggest, “I had one PRP injection it did not work, I definitely need stem cells.” That is not always the case. One injection of anything Prolotherapy, PRP, or stem cells, while possibly providing relief in many patients short-term, is typically not a long-term answer. This is explained below.

When someone sends us an email or comes into our office seeking answers as to why previous stem cell therapy treatments did not work for their knee pain, they want to know if a joint replacement is now their only option.

These emails will typically begin with:

• I used my own stem cells, my chiropractor told me they were too old and that is why my treatment did not work. I should have used “birth baby stem cells,” (placenta, umbilical cord blood, or amniotic tissue).
• Some realized that placenta, umbilical or amniotic tissue “stem cell therapy,” was not stem cell therapy at all and want to start all over again.
• Some thought that one injection of stem cells provided the answer to reversing their joint erosion. That stem cell therapy is a single shot treatment like cortisone or a one-time injection given as a series as in Hyaluronic acid injections. 

Another answer is that for some people, knee degeneration is so far gone, is so beyond repair, that knee replacement may be the only option. In our clinic, we find this type of person to be the exception and not the rule.

Degenerative knee disease does not happen overnight. Healing degenerative knee disease with stem cell therapy cannot be expected to repair decades of wear and tear as a one-time injection treatment. Failure is an over-expectation of treatment.

When you have knee joint erosion and advancing knee osteoarthritis, these conditions did not happen overnight. They took a long time to develop. When your doctor shows you your knee MRI and he/she shows you no joint space, bone spurs, degenerative soft tissue damage, these things developed over time. To have someone tell you that one injection of anything, more or less randomly given somewhere in the knee, will reverse all this damage, is an extraordinary claim that requires extraordinary evidence. That evidence is not there.

The slow degenerative disease requires slow, deliberate treatment to repair. Stem cell therapy is one treatment option. Knee replacement is another. Knee replacement is a slow methodical repair of the function of your knee requiring lengthy rehab.

What are we seeing in this image?

Here is a patient with severe osteoarthritis on the inner portions of their knees. They also have knee instability on that same side. This means that the ligaments of the knees on that side can no longer hold the shin and thigh bones in their natural alignment. The two bones are now pressing against each other and have become bone on bone on the inner side surface.

Stem cell therapy will attempt to get into the bone on bone area and regrow cartilage. But the chances may be diminished if the knee instability is not addressed.

If you put a patch on the hole, the patch will eventually wear away too

Stem cell therapy will often fail because stem cell clinicians think that if you injected the stem cells into the holes of the cartilage, they will instantly patch up the knee and the bone-on-bone situation will be gone. Maybe that will work in the short term but you still have a problem that the patch is going to be subjected to the same type of degenerative problems that caused your knee to go bone on bone in the first place. Single-injection, one-time stem cell therapy only tries to patch a hole in the cartilage. The comprehensive stem cell treatment people should have explored seeks to patch a hole in cartilage and prevent it from returning by stabilizes the knee’s ligament and tendon support structure. That is done with Prolotherapy injections which we will now discuss.

Our published research on stem cell therapy combined with Prolotherapy

When we use bone marrow-derived stem cells and Prolotherapy together:

Our 2014 study in the journal Clinical Medicine Insights. Arthritis and Musculoskeletal Disorders, (1) we examined 24 adult patients who had a diagnosis of radiographic osteoarthritis (this was degenerative knee disease which was seen and documented on an MRI) and had visited our chronic pain clinic in 2009 for Prolotherapy treatment to relieve their chronic pain. The results of our study have shown that a combined bone marrow stem cell Prolotherapy treatment regimen of injections to painful sites in and around the knee provided pain relief and improved joint function.

Paving the way for stem cell therapy success with Prolotherapy treatments

In the simplest terms, Prolotherapy is the injection of sugar water into a damaged joint. Prolotherapy injections work to heal damaged joints by stimulating nature’s healing and regenerative processes through inflammation. Prolotherapy does so by causing a controlled, specifically targeted inflammation that helps grow new ligament and tendon tissue.

Stem cell therapy is an injection of your own harvested stem cells. Stem cell therapy is typically utilized when we need to “patch” holes in cartilage and stimulate bone. We explore this option in patients when there is more advanced osteoarthritis and a recommendation for a joint replacement has been made or suggested. A realistic expectation of treatment success should be made during discussions with the provider’s office prior to the consultation.

Here are the case histories of this study:

The patient is a 69-year-old male who presented with pain in both knees.

Case history 1

• The patient is a 69-year-old male who presented with pain in both knees.
  • 4/10 on the left (30% frequency) and 7/10 on the right (90% frequency).
• The pain had begun years earlier while playing rugby and had been more severe for the four years prior to the first office visit
• Pain resulted in frequent sleep interruption and limitation of exercise. Slight flexion limitation was noted.
• The patient had received Prolotherapy from another physician for the previous two years but felt that improvement had ceased.
• The patient was diagnosed with osteoarthritis and received five bone marrow/dextrose treatments at two-month intervals in both knees.
• Two months after the final treatment, the patient reported that he was completely free of pain or stiffness in both knees, had regained full range of motion, no longer suffered sleep interruption, and was no longer limited in exercise or daily life activities.

The patient is a 56-year-old male who presented with pain in both knees.

Case history 2

• The patient is a 56-year-old male who presented with pain in both knees.
• The patient is a former competitive weightlifter who continues to do strength training exercises.
• He complained of instability in both knees during exercise, as well as sleep interruption.
• The patient received 29 bilateral dextrose prolotherapy treatments over five years to the knee. At the final prolotherapy visit, sleep interruption was still present, pain intensity was 4/10, and pain frequency was 100%.
• Four months later, the patient was treated with platelet-rich plasma. Three months after plasma treatment, the patient began a series of three bone marrow stem cell injection treatments (without dextrose prolotherapy) at 2–3 month intervals. At the time of the second bone marrow stem cell injection treatments, stability was improved.
• At the time of the third treatment, pain intensity was 2/10, and pain frequency was 30%. Sleep was no longer affected. These gains were maintained for nine months.

The patient is a 69-year-old female with pain in both knees.

Case history 3

• The patient is a 69-year-old female with pain in both knees.
• She had been previously diagnosed with osteoarthritis, had arthroscopic surgery to both knees eight years earlier, and bilateral medial meniscus surgery 15 years earlier.
• Pain occurred climbing or descending stairs and with standing or walking for two hours. Pain interrupted sleep and limited participation in racquet sports and golf.
  • Pain intensity was 4/10 in the left knee and 5/10 in the right.
• The patient received six bilateral treatments with dextrose prolotherapy over a ten-month period. After the first month of this period, the patient reported uninterrupted sleep, pain intensity of 2/10, resumption of limited golf, and an overall improvement of 50%–55%.
• One year after the final prolotherapy, pain intensity had returned to 4/10 with a frequency of 20%, and sleep interruption had resumed. At this time, the patient received the first of two bone marrow stem cell injection treatments with dextrose Prolotherapy treatments, five months apart.
• At the time of the second treatment, pain intensity was 1/10 with a frequency of 20%, sleep interruption was reduced by half, and patient-reported overall improvement was 90%. Eight months following the final treatment, the patient reported being free of pain and able to resume full participation in all of her usual athletic activities.

More research on bone marrow concentrate alone

Others have cited this research in their own studies. A February 2020 study in the Orthopaedic Journal of Sports Medicine (2) cited our research as well as the work of many others in comparing “which is better” Platelet Rich Plasma (PRP) or bone marrow concentrate?

In their findings, they observed: “Both PRP and bone marrow concentrate were effective in improving patient-reported outcomes in patients with mild to moderate knee osteoarthritis for at least 12 months; neither treatment provided a superior clinical benefit. (Meaning that they provided about equal benefit with one treatment not being that much better than the other). Autologous (from your own blood) PRP and bone marrow concentrate showed promising clinical potential as therapeutic agents for the treatment of osteoarthritis, and while PRP has strong clinical evidence to support its efficacy, bone marrow concentrate has limited support. This study did not prove bone marrow concentrate to be superior to PRP.”

Let’s also note in this study that the participants received one injection of PRP and one injection of bone marrow concentrate. That was the extent of the treatment. Then the study’s patients were asked at one, three, six, nine, and twelve months how did their knee feel? So this study compared one injection of each.

A 2018 paper published in the journal Clinical Medicine Insights. Arthritis and Musculoskeletal Disorders (3) also cited our published study.

In this study, more injections were given. Here is what these researchers wrote:

“The aim of this study was to build on this preliminary research (such as ours) by reporting the short-term progress of 15 patients (20 knees) with knee osteoarthritis through 4 bone marrow concentrate treatments.”

Here the study participants had four bone marrow concentrate treatments. They had

• First treatment
• Approximately 14 days later they had a second treatment
• The third treatment twenty-one days later (35 days after the first treatment)
• The fourth treatment about 34 days after the third treatment (about 10 weeks after the first treatment)
• On average the patient received four treatments in 70 days or 10 weeks.

About two weeks later or eighty-six days after treatment began patients were assessed for “resting pain, active pain, lower functionality scale, and overall improvement percentage were compared after each treatment.”

The published results of this study found:

“Patients experienced statistically significant improvements in active pain and functionality score after the first treatment. Additionally, patients experienced a mean decrease in resting pain after the first treatment, yet outcomes were not statistically significant until after the second treatment. On average, patients experienced an 84.31% decrease in resting pain, a 61.95% decrease in active pain, and a 55.68% increase in functionality score at the final follow-up. Patients also reported a mean 67% total overall improvement at study conclusion.”

What this research suggests are similar findings to our own. Patients should have an expectation that more than one treatment will be needed to help them achieve their treatment goals.

In this video

In this video Ross Hauser, MD discusses when Bone Marrow Aspiration or stem cell therapy would be preferred. In this video, he demonstrates bone marrow aspiration from the iliac crest while explaining the various conditions this technique can be used to treat.

Questions about our treatments?

We hope you found this article informative and it helped answer many of the questions you may have surrounding these various injection treatments. Do you want to ask about treatment for your knees? If you have questions and want to know how we may be able to help you, please contact us and get help and information from our Caring Medical staff.

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References:

1 Hauser RA, Orlofsky A. Regenerative injection therapy with whole bone marrow aspirate for degenerative joint disease: a case series. Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders. 2013 Jan;6:CMAMD-S10951. [Google Scholar]
2 Anz AW, Hubbard R, Rendos NK, Everts PA, Andrews JR, Hackel JG. Bone marrow aspirate concentrate is equivalent to platelet-rich plasma for the treatment of knee osteoarthritis at 1 year: a prospective, randomized trial. Orthopaedic journal of sports medicine. 2020 Feb 17;8(2):2325967119900958. [Google Scholar]
3 Shaw B, Darrow M, Derian A. Short-term outcomes in treatment of knee osteoarthritis with 4 bone marrow concentrate injections. Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders. 2018 Jun 14;11:1179544118781080. [Google Scholar]

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• Surgery
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• R.I.C.E.