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Prolotherapy

Ross Hauser, MD

Ross Hauser, MD: the use of Stem Cell Therapy in the treatment of joint and spine degeneration.

Stem cell therapy is exploding in the medical field, and for good reason. Stem cells have the potential to regenerate into any type of body tissue.  The amazing thing about stem cells is that when you inject them into the body, they know what kind of cells your body needs – for example, meniscus cells or cartilage cells.  It is a very exciting time for medicine, especially in the field of regenerative medicine. In our office we often refer to this as Cellular Prolotherapy.

In Stem Cell Therapy we use a person’s own healing cells from bone marrow, fat, and blood (alone or in various combinations) and inject them straight to the area which has a cellular deficiency.

The goal is the same: to stimulate the repair of injured tissues. Stem cells aid in fibroblastic proliferation where cell growth, proteosynthesis, reparation, the remodeling of tissues, and chondrocyte proliferation occurs. Our bone marrow contains stem cells, also termed mesenchymal stem cells and progenitor cells, among other names. These immature cells have the ability to become tissues like cartilage, bone, and ligaments.

Consequently, researchers and clinicians are focusing on alternative methods for cartilage preservation and repair. Recently, cell-based therapy has become a key focus of tissue engineering research to achieve functional replacement of articular cartilage.1

Stem Cell Therapy or Prolotherapy?


Not all injuries require stem cells to heal. For many patients the success rate with traditional Prolotherapy in this office is in the 90%+ range for all patients. However, for those cases of advanced arthritis, meniscus tears, labral tears, bone-on-bone, or aggressive injuries, our Prolotherapy practitioners may choose to use stem cell injections to enhance the healing, in combination with dextrose Prolotherapy to strengthen and stabilize the surrounding support structures for meniscus repair.

In our research published in The Open Stem Cell Journal, Rationale for Using Direct Bone Marrow Aspirate as a Proliferant for Regenerative Injection Therapy (Prolotherapy).

We not only showed the benefit of bone marrow derived stem cells as a Prolotherapy proliferant solution, but also that this exciting field of medicine needs doctors and scientists working together to expand research and technique guidelines.

Typically the tissue that we are trying to stimulate to repair with Stem Cell Therapy or Cellular Prolotherapy is articular cartilage, but we can also proliferate soft tissues structures such as ligament and tendons. This is new technology so we are studying it as we use it to treat patients.



Stem Cell Therapy Injection Research


Recent research conducted, “Transplanted bone marrow mesenchymal stem cells with platelet-rich fibrin glue scaffold stimulates full-thickness cartilage defects to heal.”

We chose to review this study to support our research and to inform people about the human studies using bone marrow stem cells for articular cartilage lesions. Articular cartilage is a type of cartilage that covers joint surfaces and is most susceptible to injury compared to other types of cartilage.

Researchers at Cairo University School of Medicine and the University of Pittsburgh School of Medicine reported on the use of bone marrow mesenchymal stem cells and a platelet-rich fibrin scaffold to heal full-thickness cartilage defects in five patients. The researchers studied the treatment results from the bone marrow mesenchymal stem cells which were used in a platelet rich fibrin glue, placed on the tear and covered with a flap of the patients cartilage.


Why use Bone Marrow Stem Cells in Prolotherapy?


Articular Cartilage has limited repair capacity and marrow-stimulation procedures such as microfracture, osteochondral grafts and autologous cartilage implantations have had limited success in articular cartilage defects.4

The researchers from this study chose mesenchymal stem cells from bone marrow because these have the ability to differentiate into cartilage cells. In the case of these five patients the bone marrow was harvested from the iliac crest (hip bone).

Platelets were used as a scaffold because platelets contain various growth factors that stimulate cartilage regeneration. The researchers expected that the biological effect of multiple growth factors on tissue regeneration is greater that of a single growth factor.

Results

The patients showed significant functional improvement. Two of the patients underwent arthroscopy after the transplantation and showed near normal articular cartilage. Three postoperative MRIs revealed complete healing and congruent cartilage tissue, whereas two patient MRIs showed incomplete congruity in the cartilage tissue.

Conclusion


The researchers concluded that the transplantation of autologous culture-expanded bone marrow-mesenchymal stem cells in platelet rich-fibrin glue shows great promise in the treatment of full-thickness articular cartilage defects, particularly large-sized defects (>4 cm).  The positive 1 year clinical outcomes support further randomized controlled clinical trials of this treatment modality with larger numbers of patients and longer follow-up periods.

We use bone marrow in a more direct, non-surgical way to regenerate cartilage


Bone Marrow Prolotherapy involves direct bone marrow aspiration (or also concentrated) to get the stem cells to the site of the injury. Does the study above suggest that direct bone marrow injections without culture expanded and without the scaffold would work?  Possibly, but only time will tell as research progresses. But in our experience we have discovered that these stem cells act as great proliferant solutions for Prolotherapy. We use bone marrow stem cells in conjunction with other Prolotherapy solutions to treat large articular defects in the labrum and meniscus areas. Typically, patients are seen every two months. Most patients need 3-6 visits. The good news is during the time of healing, the patient can exercise and start getting back into great shape! Bone marrow and adipose-derived stem cell therapies are gaining in recognition and we are happy to offer them as an option for treating chronic injuries and sports injuries.

Research into the efficacy of any treatment protocol and stem cell injection therapy


There is always conflicting research into the efficacy of any treatment protocol and stem cell injection therapy is no different. Many times a patient will point to his or her own clinical dissatisfaction or research and say, stem cell therapy does not work as well as advertised. Let’s look at some of that research:

“Osteoarthritis  is a cartilage degenerative process…No treatment is still available to improve or reverse the process. Stem cell therapy opened new horizons for treatment of many incurable diseases…In this research four patients with knee osteoarthritis were selected for the study. They were aged 55, 57, 65 and 54 years, and had moderate to severe knee Osteoarthritis. After their signed written consent, 30 mL of bone marrow were taken and cultured for MSC growth. After having enough MSCs in culture (4-5 weeks) and taking in consideration all safety measures, cells were injected in one knee of each patient.

The walking time for the pain to appear improved for three patients and remained unchanged for one. On physical examination, the improvement was mainly for crepitus. It was minor for the improvement of the range of motion.

Results were encouraging, but not excellent. Improvement of the technique may improve the results.”4

Improvement in technique Platelet Rich Plasma Therapy combined


We agree that stem cell therapy has benefits but may not provide a full cure. This is why we recommend the use of Platelet Rich Plasma Therapy in conjunction with stem cell therapy. The study above involved cultured stem cells. In our opinion Stem cell therapy is more effective if the stem cells are given better direction. This is where the growth factors in blood platelets can be very effective. Platelets aid the stem cells in their various jobs including differentiation and then aid in the differentiated cells making the extracellular matrix to repair the injured tissue.

Platelet Rich Plasma contains a myriad of substances that stimulate healing:

Numerous studies have shown that PRP enhances the effects of Stem Cell Therapy5,6 As the study above notes – “Results were encouraging, but not excellent. Improvement of the technique may improve the results.” Platelet Rich Plasma therapy improves the technique and improves the results.


The goal of Stem Cell Therapy – Cellular Prolotherapy

Our ultimate goal with all forms of Prolotherapy is to get the patients back to doing the things that they want to do without pain. It is our hope that the Stem Cell Therapy (Cellular Prolotherapy) treatments will form functionally, structurally, and mechanically equal to, if not better than, living tissue which has been designed to replace (or work alongside of) damaged tissue. It is hard to prove the above statement because we cannot sacrifice human beings after Prolotherapy to see if the tissue looks and acts normally. We can, however, report that the majority of our patients who receive Stem Cell Therapy along with traditional Hackett-Hemwall Prolotherapy get back to activities and have dramatically decreased pain levels using this comprehensive approach.

Links to our other articles for your specific conditions

Stem Cell Therapy for Back Pain

A page with more information on stem cell injection treatments combined with Prolotherapy and PRP Treatments for back pain.

Stem Cell Therapy for Knee Osteoarthritis

In this article we  discusses research that shows thatstem cell injection therapy will aid in the repair of articular cartilage and meniscus tears. The treatment relieves symptoms of stiffness, pain, disability, and inability to walk as commonly reported by our patients diagnosed with knee osteoarthritis.


References for this article

1. Mazor M, Lespessailles E, Coursier R, et al. Mesenchymal stem-cell potential in cartilage repair: an update. J Cell Mol Med. 2014 Oct 29. doi: 10.1111/jcmm.12378. [Pubmed]
2. Diekman BO, Guilak F. Stem cell-based therapies for osteoarthritis: challenges and opportunities. Curr Opin Rheumatol. 2013 Jan;25(1):119-26. [Pubmed]
3. Hauser RA, Orlofsky A. Regenerative injection therapy with whole bone marrow aspirate for degenerative joint disease: a case series. Clin Med Insights Arthritis Musculoskelet Disord. 2013 Sep 4;6:65-72. doi: 10.4137/CMAMD.S10951. eCollection 2013. [Pubmed]
4. Davatchi F, Abdollahi BS, Mohyeddin M, Shahram F, Nikbin B. Mesenchymal stem cell therapy for knee osteoarthritis. Preliminary report of four patients. Int J Rheum Dis. 2011 May;14(2):211-5. [Pubmed]
5. Mishra A, Tummala P, King A, Lee B, Kraus M, Tse V, Jacobs CR. Buffered platelet-rich plasma enhances mesenchymal stem cell proliferation and chondrogenic differentiation. 2009 Sep;15(3):431-5.
6. Kasten P, Vogel J, Beyen I, Weiss S, Niemeyer P, Leo A, Lüginbuhl R. Effect of platelet-rich plasma on the in vitro proliferation and osteogenic differentiation of human mesenchymal stem cells on distinct calcium phosphate scaffolds: the specific surface area makes a difference. J Biomater Appl. 2008 Sep;23(2):169-88. Epub 2008 Jul 16. [Pubmed]

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