Prolotherapy Research Regeneration Articular Cartilage

Ross Hauser, MDRoss Hauser, MD
As research is being published on articular cartilage regeneration, it is becoming apparent that a combination of Prolotherapy, Platelet Rich Plasma (PRP) therapy, and Stem Cell Therapy is an effective treatment for cartilage regeneration.

Research for PRP and Stem Cell Therapy

Older tenets of medicine state that cartilage cannot be repaired. These tenets are being challenged in both human and animal studies. Researchers in Korea found that rabbits with osteoarthritis of the knees treated with intra-articular PRP injection showed cartilage regeneration in all severities of rabbit knee osteoarthritis. The cartilage regenerative power of PRP injection in moderate knee osteoarthritis was greater than that in mild or very mild osteoarthritis. In other words the worse degeneration of cartilage the better PRP worked. 1

In addition to PRP, new research is confirming Mesenchymal Stem Cell Therapy has shown significant promise for the repair or regeneration of damaged cartilage: “mesenchymal stem cells (MSCs) have great potential owing to their ability to create a reparative environment.” 2 In other newly published research the combination of stem cells and PRP were shown safe, effective, and reduced pain and improved function in patients with knee osteoarthritis.3 Other research states, that lthough surgical and pharmaceutical interventions are currently available for treating  osteoarthritis, restoration of normal cartilage function has been difficult to achieve. Bone marrow-derived ‘mesenchymal stem cells’ or ‘mesenchymal stromal cells appear to be ideally suited for therapeutic use in cartilage regeneration.4

Prolotherapy Research Regeneration Articular Cartilage

While Platelet Rich Plasma Therapy and Adult Stem Cell Therapy are providing a lot of excitement in the orthopedic community, they are not always and necessarily the first line of treatment we suggest.

In the Journal of Prolotherapy, we introduced research that confirmed articular cartilage regeneration in five patients with Osteoarthritis. Here is our summation: “Prolotherapy improved the pain and function in five knees with osteoarthritis. All five degenerated knees showed evidence of articular cartilage regeneration in their standard weight-bearing X-rays after Prolotherapy. It is suggested that before and after X-ray studies can be used to document the response of degenerated joints to Prolotherapy.” 5

So how do we decide if Prolotherapy, Platelet Rich Plasma Therapy, or Stem Cell Therapy is the best course of treatment for a patient? The decision is made in the office following a physical examination and detailed patient history. Each chronic pain patient has an individual case with individual needs requiring an individual approach.

Bone Marrow Stem Cells for Articular cartilage repair

A pilot study is one where a small number of patients are given a specific therapy. If the treatment works then the authors recommend future studies on larger amounts of patients. Doctors at Cairo University in Egypt performed a pilot study involving stem cells from the bone marrow of the patient receiving treatment. The stem cells were transplanted on a platelet-rich fibrin glue and used in cartilage defects of the patients. The results showed that this therapy helped heal articular cartilage defects in a small group of patients.6 Five patients with full-thickness femoral condyle articular cartilage defects were treated with placing platelet-rich fibrin glue into the lesions and then placing culture-expanded autologous bone marrow mesenchymal stem cells. MRI’s were done after twelve months. MRI of 3 patients at 12 months postoperatively revealed complete defect fill and complete surface congruity with native cartilage, whereas that of 2 patients showed incomplete congruity.

The clinical scores showed statistically significant improvement at both times. Two of the patients had repeat arthroscopy and both showed significant improvement, with one of the arthroscopies showing an almost completely healed articular cartilage. The authors concluded that “autologous bone marrow with mesenchymal stem cell transplantation on a platelet-rich fibrin glue as a cell scaffold may be an effective approach to promote the repair of articular cartilage defects of the knee in human patients.6”1

Bone Marrow Growth Factors

To me, this was a very good paper and worthy of reading. Again, though the doctors are orthopedic surgeons and want to do surgery on everything. Why not have a control group that received injected stem cells without any surgery? My thoughts are it would have worked anyway, because the body knows best. The authors noted that the platelet granules of platelets contain transforming growth factor (TGF-B1) and insulin growth factor-1 (IGF-1), which both stimulate cartilage regeneration. This was one of the main points as to why they chose platelets as a scaffold. Of course a scaffold would have to be surgically placed.

Bone marrow is full of IGF-1 and TGF-B1.  7,8 Just about any growth factor is available in ample amounts in bone marrow. Want some FBS, PDGF, VEGF, IGF-1, IL-8, BMP-4 and others, it will be found in bone marrow. How does Bone Marrow Prolotherapy compare to the therapy done in the study? Direct Bone Marrow Prolotherapy does not use a scaffold, rather the stem cells from the patient’s bone marrow are injected directly into the patient’s injury. When one does direct Bone Marrow Prolotherapy as stem cell therapy, you are letting the body produce what it needs. You are not making it. If the body needs chondrocytes, I suspect it will make them from the stem cells found in bone marrow. How? Well the way it normally does, by differentiating stem cells into chondrocytes. These newly made chondrocytes need nutrition from the joint fluid, so if the degenerated joint lacks joint fluid the aspirated bone that was injected into the joint will stimulate joint fluid production via the synoviocytes. Yes there are studies that show stem cells go all over synoviocytes and are found in abundance in the synovium.

So yes, this first study reviewed was a good one. Articular cartilage can definitely be regenerated, I just say we do it without surgical intervention.

Do you have questions about Articular Cartilage Regeneration? Ask us.

1. Kwon DR, Park GY, Lee SU. The effects of intra-articular platelet-rich plasma injection according to the severity of collagenase-induced knee osteoarthritis in a rabbit model. Ann Rehabil Med. 2012 Aug;36(4):458-65. Epub 2012 Aug 27.

2 Bulman SE, Barron V, Coleman CM, Barry F. Enhancing the Mesenchymal Stem Cell Therapeutic Response: Cell Localization and Support for Cartilage Repair. Tissue Eng Part B Rev. 2012 Sep 24. [Epub ahead of print]

3. Koh YG, Choi YJ. Infrapatellar fat pad-derived mesenchymal stem cell therapy for knee osteoarthritis. Knee. 2012 May 12. [Epub ahead of print]

4. Gupta PK, Das AK, Chullikana A, Majumdar AS. Mesenchymal stem cells for cartilage repair in osteoarthritis. Stem Cell Res Ther. 2012 Jul 9;3(4):25. [Epub ahead of print]

5. Hauser RA, Cukla JJ. Standard Clinical X-ray Studies Document Cartilage Regeneration in Five Degenerated Knees After Prolotherapy. Journal of Prolotherapy. 2009;1:22-28.

6. Haleem AM. The clinical use of human culture-expanded autologous bone marrow mesenchymal stem cells transplanted on platelet-rich fibrin glue in the treatment of articular cartilage defects: a pilot study and preliminary results.

7. Mishima Y. Chemotaxis of human articular chondrocytes to mesenchymal stem cells. Journal of Orthopedic Research. 2008;26:1407-1412.

8. Smiler D. Growth factors and gene expression of stem cells: bone marrow compared with peripheral blood. Basic and Clinical Research. 2010;19:229-240.

Prolotherapy research citations for other joint pain problems. An article by Ross Hauser, MD.