Why stem cell therapy did not work for your knee pain

Ross Hauser MD

Ross Hauser, MD

When someone sends us an email or comes into our office seeking answers to why previous stem cell therapy treatments did not work for their knee pain, they want an explanation.

The loose ligaments and tendons of a wobbly, hypermobile knee. The culprits of failed stem cell therapy.

But in the end, we find that the treatments these patients received could not maintain the repair needed in a knee that swims in a toxic soup of inflammation born from knee instability caused by unnatural shear forces and destructive joint motion.

In other words, the loose ligaments and tendons of a wobbly, hypermobile knee, which causes advanced degenerative wear and chronic inflammation, were not treated.

The stem cell therapy these people received tried to patch a hole in the cartilage. The comprehensive stem cell Prolotherapy treatment they 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.

The cartilage would have a chance to repair if the destructive motion of the knee that created the hole and the bone on bone situation was fixed too.

Before we get further into this discussion, people need to know that despite the best intention of a surgeon, many joint replacements do not work. Despite the best intention of conservative care, hyaluronic acid, cortisone injections, anti-inflammatory medications, and physical therapy do not always work.

A toxic knee environment kills stem cells

A healthy knee is surrounded by a healthy soup of nutrients and synovial fluid. The synovial fluid is a thick gel-like liquid that helps cushion the knee and acts to absorb the daily impact of walking, running and stair climbing our knees are subjected to. 

As we get older or suffer from repetitive injury or overuse syndrome, the healthy protective synovial fluid and the nutrient soup becomes poisoned with the toxins of inflammation.

The obvious signs of the body’s attempt to stop these destructive forces and stabilize the knee and stop the damage is SWELLING. 

Inflammation is a state of emergency reacting to destructive joint motion

Nature created a powerful inflammatory system in all of us to act quickly, decisively and aggressively to repel disease and heal injury. You need inflammation to get over the flu, you need inflammation to heal a wound, you need inflammation to fix a damaged joint. Inflammation is filled with oxidants and chemical stimulants that take control of the injury site and puts the area into a “state of emergency.” As with all “States of Emergency,” the inflammation authorities take over communication, the highways and shut down secondary vital services. These are necessary actions inflammation must take to stop destructive joint motion and to reroute energy into healing (inflammation). The longer the state of emergency, (the inflammation) exists, the longer the knee swims in a toxic soup of oxidants and toxic chemicals. A knee cannot continuously maintain a state of emergency.

Degenerative Arthritis

What happens to the knee as it sits long-term in a toxic soup of oxidants and chemicals?

Stem cells do have the ability to change this degenerative toxic environment into a regenerative healing environment, but sometimes they can’t do it themselves

However, the stem cells can be bogged down and the messages blurred by the toxic soup, so repair can take longer and be more challenging, if at all.

In a 2017 study, Dr. Ming Pei of West Virginia University  publishing in the medical journal Biomaterials suggests that while adult stem cells are a promising cell source for cartilage regeneration, increasing evidence indicates that environmental preconditioning is a powerful approach in promoting stem cells’ ability to resist a harsh environment such as hypoxia (the lack of oxygen) and inflammation, even that following surgery.(1)

What are examples of “environmental preconditioning?” 

Paving the way for stem cell success with Prolotherapy

In the study above the idea is to get the stem cells ready to more efficiently heal by changing their conditioning and the joint environment by removing oxidative stress in the joint. You start this by rebooting the repair process. You fight inflammation with inflammation. Prolotherapy injections can provide that inflammation that reboots the chronic inflammation into acute inflammation. Acute inflammation is short-term.

Prolotherapy in the toxic knee environment – making stem cells work

One important published paper on stem cell research from Purdue University confirmed the notion that dextrose, especially hypertonic dextrose is a significant factor in the ability of mesenchymal stem cells from bone marrow to proliferate.(2)

The mesenchymal stem cell consumption of glucose increased proportionally with the glucose concentration in the medium. The higher the glucose concentration in the medium, the greater the glucose consumption by the bone marrow stem cells. The primary results note that the higher glucose and serum concentrations appear to produce higher cell populations over time.

The cells of the body obtain their energy via aerobic metabolism. In other words, cells need to “breathe” to make their energy. Stem cells cannot make energy in  toxic knee environment. They need oxygen and food.

Treating the whole knee with Prolotherapy and stem cells brings oxygen and glucose that makes stem cells grow and repairs the ligaments and tendons that stops the hypermobility that creates destructive joint forces.


Changing the focus from stem cells for damaged cartilage to treating the whole knee

Doctors in Iran are among the leading researchers when it comes to the problems of the knee and their regenerative medicine solutions. Listen to this research from doctors at Tabriz University of Medical Sciences, publishing in the prestigious international journal Therapeutic advances in musculoskeletal disease, published in London.

In this research doctors explored the use of simple dextrose Prolotherapy for problems of knee osteoarthritis. Here 24 female patients were followed after treatment. The results:

Prolotherapy with three intra-articular injections of hypertonic dextrose given four weeks apart for selected patients with knee osteoarthritis, resulted in significant improvement of validated pain, range-of-motion, and WOMAC-(post-treatment questionnaire based function scores), when baseline levels were compared at 24 weeks.

But while the documented success of dextrose Prolotherapy in treating knee osteoarthritis is a great validation for the treatment, the best part of the research was the acknowledgement that these doctors would have had greater success had they treated the whole knee. Listen to this, remember, the results of the study showed benefits of Prolotherapy for knee osteoarthritis:

Studies have reported that the (Prolotherapy) improvements reduce over time and sometimes the symptoms are worse after several months, which indicate the short-term effects of the treatment, similar to the injections of hyaluronic acid agents. Though post-treatment pain is not as severe as their experienced original pretreatment pain, this could suggest that these patients need several injections at intervals to keep the desired results.

Here is the extraordinary part:

“Ignoring the patient’s other pain sources including joint-surrounding tendons and ligaments could be another potential cause in this regard; we did not treat enthesopathies or the ligament fibro-osseous junctions with extra-articular dextrose injections around these elements in our study. So, it appears that ligaments or other structures need to be treated to get the full benefit from Prolotherapy.”(3)

You need to treat the whole knee. The primary reasons  why Prolotherapy and stem cell therapy will not achieve the desired results:

“(In this study) extra-articular injection (those to the outer and surrounding ligaments and tendons)  in addition to intra-articular injection (directly into the knee meniscus and cartilage area) was not included in the research protocol.

“In other words, the first priority in our study was a focus on the damaged cartilage and not on external ligaments or tendons. However, this would be a promising method for showing the better efficacy of prolotherapy, especially for young or middle-aged patients with ligament injury, and even for elderly patients with knee osteoarthritis in whom lateral collateral ligament (LCL) damage is not uncommon.”(3)

More validation for treating the whole knee

In this study, doctors from the University of Tehran compared results in patients who received Prolotherapy with dextrose periarticular injections around the knee joint with patients who received Prolotherapy intra-articular injections. In other words, one group received injections around the knee joint, another group received injections directly into the knee joint.

Simply, Prolotherapy for knee osteoarthritis is not a single or few injections, it is many injections. For stem cell therapy to achieve its best chance of success you need to treat the whole joint.

Do you want to ask about your stem cell treatment for your knees? Get help and information from our Caring Medical staff

1. Pei M. Environmental preconditioning rejuvenates adult stem cells’ proliferation and chondrogenic potential. Biomaterials. 2017 Feb;117:10-23. doi: 10.1016/j.biomaterials.2016.11.049. Epub 2016 Nov 25. [Google Scholar.]

2 Deorosan B, Nauman EA. The Role of Glucose, Serum, and Three-Dimensional Cell Culture on the Metabolism of Bone Marrow-Derived Mesenchymal Stem Cells. Stem Cell International. 2011;  Article ID 429187, 12 pages. Doi:10.4061/2011/429187

3 Eslamian F, Amouzandeh B. Therapeutic effects of prolotherapy with intra-articular dextrose injection in patients with moderate knee osteoarthritis: a single-arm study with 6 months follow up. Therapeutic Advances in Musculoskeletal Disease. 2015;7(2):35-44. [Google Scholar]

4 Rezasoltani Z, Taheri M, Mofrad MK, Mohajerani SA. Periarticular dextrose prolotherapy instead of intra-articular injection for pain and functional improvement in knee osteoarthritis. Journal of Pain Research. 2017;10:1179-1187. [Google Scholar]

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