Stem Cell Prolotherapy for knee cartilage regeneration

Dr. David Woznica ProlotherapistDavid N. Woznica, MD 

In this article we will examine the research and the clinical application of stem cell therapy for articular cartilage repair. Stem cell therapy will be explained in the various videos embedded in this article.

If you have  question about cartilage repair and injectable stem cell treatments, please get help and information for our Caring Medical staff.

In early 2017, doctors in China writing in the medical journal Stem cells international wrote that “Although the role of stem cells in cartilage regeneration is certain, the mechanism underlying this process in cartilage repair is not yet clear. The full range of limitations and possibilities, with respect to clinical application of various stem cells, remains to be established, but the advantages of stem cells seem obvious.”(1)

What does all this mean? 

The “certain” ability of stem cell therapy to regenerate articular cartilage has been documented by a series of landmark studies published over the more than last two decades.

In a 1994 landmark study from the Department of Orthopaedics, Case Western Reserve University School of Medicine, University Hospitals of Cleveland, doctors found that osteochondral progenitor cells (in simple terms stem cells that accelerate and enhance bone and articular cartilage repair) could be used to repair large, full-thickness defects of the articular cartilage that had been created in the knees of rabbits.

Of note:

The researchers concluded: The current modalities (in 1994 knee cartilage surgery and conservative care, medications and painkillers) for the repair of defects of the articular cartilage have many disadvantages. The transplantation of progenitor (stem) cells that will form cartilage and bone offers a possible alternative to these methods.(2)

In 2014, Dr. Shinya Yamasaki who lead the above cited 1994 study twenty years earlier, lead another study, this time from the Department of Orthopaedic Surgery, Sinshu University School of Medicine, Japan.

In this study again, the doctors found that there is no widely accepted method to repair articular cartilage defects. Bone marrow mesenchymal cells have the potential to differentiate into bone, cartilage, fat and muscle. Bone marrow mesenchymal cell transplantation is easy to use clinically because cells can be easily obtained and can be multiplied without losing their capacity of differentiation. The objective of this study was to apply these cell transplantations to repair human articular cartilage defects in osteoarthritic knee joints.(3)

In a heavily cited 2003 study from Osiris Therapeutics in Baltimore, doctors reported significant improvement in medial meniscus and cartilage regeneration with autologous stem cell therapy in an animal model. Not only was there evidence of marked regeneration of meniscal tissue, but the usual progressive destruction of articular cartilage, osteophytic remodeling and subchondral sclerosis (hardening of the bone beneath the cartilage) commonly seen in osteoarthritic disease was reduced in MSC-treated joints compared with controls.(4)

In 2016, doctors at Georgia Regents University writing in the medical journal Clinical and translational medicine opened their paper by saying that recent development in stem cell tissue engineering has created a lot of excitement in the field of cartilage regeneration biology.

Part of the excitement was the discovery that stem cells could control various healing mechanisms that enabled articular cartilage repair. This includes the capability to inhibit T cell growth, thus showing that they have the ability to down-regulate the natural inflammatory response in osteoarthritis.

In addition to stem cells capacity to both differentiate into new cartilage cells as well as suppress inflammation, recent studies have found that stem cells can also combat osteoarthritis through paracrine mechanisms. They release important cytokines such as epidermal growth factor (EGF), transforming growth factor beta (TGFB), vascular endothelial growth factor (VEGF), as well as other cytokines and new cartilage proteins that are essential in combating osteoarthritis and degenerative processes. It has also been suggested that stem cells could release cytokines and proteins that could help combat neurogenic pain, which would have numerous benefits in treating osteoarthritis pain.(5)

In one peer-reviewed article from Japanese researchers at the Department of Hand Surgery, Nagoya University Graduate School of Medicine on articular cartilage defects in rabbits, the authors showed that direct mesenchymal stem cell injections stimulated articular cartilage repair.

The authors were not trying to prove that direct bone marrow injection stimulates articular cartilage defects to heal, because they used the direct mesenchymal stem cell injection as a control. The study went as follows: full-thickness osteochondral defects (5mm x 5mm wide, 3mm deep) were created in the trochlear groove of the femurs in adult rabbits. The defect was filled with synovial mesenchymal cells suspension and then as controls, some of the cells were directly injected into the joint or nothing was done at all. They were examining the results of directly filling the defect compared to just injecting mesenchymal stem cells intra-articularly versus doing nothing at all.

In total 36 rabbits’ knees were examined macroscopically, histologically, as well as under the microscope with fluorescent dye (the mesenchymal stem cells were tagged with a dye to identify them.)

Stem Cell Prolotherapy for knee cartilage regenerationThe knees were examined at 12 weeks and 24 weeks.

In the control group of animals where nothing was done, the articular cartilage defect remained, but in the intra-articular group as well as the group of animals where the mesenchymal stem cells were placed directly on the wound, the defects were completely covered by new articular cartilage tissue.

In the directly placed group, the regenerated cartilage matrix was well developed. In other words, at 6 months, the intra-articular stem cell therapy group was regenerating articular cartilage, but it wasn’t at the level of the normal cartilage, whereas when the stem cells were placed directly on the wound, the process was taking place at a faster rate.

Our Research: Caring Medical and Rehabilitation Services published studies

Hauser R, Eteshola E. Rationale for using direct bone marrow aspirate as a proliferant for regenerative injection therapy (prolotherapy). The Open Stem Cell Journal. 2013;4:7-14.

In this research Ross Hauser MD found: Initial observations using whole bone marrow injections in conjunction with dextrose prolotherapy for treatment of  osteoarthritic joints suggest that the procedure is safe and effective. Treatment courses of less than 12 months are associated with substantial gainsin pain relief and functionality. Read full Article


Treating Osteoarthritic Joints Using Dextrose Prolotherapy and Direct Bone Marrow Aspirate Injection Therapy

Ross Hauser, MD, Woldin B. Treating osteoarthritic joints using dextrose prolotherapy and direct bone marrow aspirate injection therapy. The Open Arthritis Journal. 2014;7:1-9.Osteoarthritis is a chronic, progressive disease of the articular joints, and to date, has no cure or effective long-term treatment.

Results: Patient-reported improvements in pain relief and joint function were statistically significant (P < .001), as were gains in activities of daily living, exercise ability, and range of motion and losses in stiffness and crepitus. No adverse events occurred.

Conclusion: Our survey of patient-reported outcomes supports the use of bone marrow Prolotherapy as an effective therapy for treating osteoarthritis and suggests that BMP has potential for enhancing the quality of life of individuals with the disease.Read full Article


Bone Marrow Prolotherapy for Degenerative Joint Disease

Regenerative Injection Therapy with Whole Bone Marrow Aspirate for Degenerative Joint Disease: A Case Series

Hauser R, 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;6:65-72.

In this study patients reported improvements with respect to pain, as well as gains in functionality and quality of life. Three patients, including two whose progress under other therapy had plateaued or reversed, achieved complete or near-complete symptomatic relief, and two additional patients achieved resumption of vigorous exercise. These preliminary findings suggest that osteoarthritis treatment with whole bone marrow aspirate injection merits further investigation…Read full Article

Do you have  questions about cartilage repair and injectable stem cell treatments, please get help and information for our Caring Medical staff

1 Wang M, Yuan Z, Ma N, Hao C, Guo W, Zou G, Zhang Y, Chen M, Gao S, Peng J, Wang A. Advances and Prospects in Stem Cells for Cartilage Regeneration. Stem cells international. 2017 Jan 26;2017. [Google Scholar]

2 Wakitani S, Goto T, Pineda SJ, Young RG, Mansour JM, Caplan AI, Goldberg VM. Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage J. Bone Joint Surg. Am. 1994;76:579-92.  [Google Scholar]

3. Yamasaki S, Mera H, Itokazu M, Hashimoto Y, Wakitani S. Cartilage repair with autologous bone marrow mesenchymal stem cell transplantation: review of preclinical and clinical studies. Cartilage. 2014 Oct;5(4):196-202.  [Google Scholar]

4. Murphy JM, Fink DJ, Hunziker EB, Barry FP. Stem cell therapy in a caprine model of osteoarthritis. Arthritis & Rheumatology. 2003 Dec 1;48(12):3464-74.  [Google Scholar]

5. Burke J, Hunter M, Kolhe R, Isales C, Hamrick M, Fulzele S. Therapeutic potential of mesenchymal stem cell based therapy for osteoarthritis. Clinical and translational medicine. 2016 Aug 10;5(1):27.  [Google Scholar]

6. Tatebe M, Nakamura R, Kagami H, Okada K, Ueda M. Differentiation of transplanted mesenchymal stem cells in a large osteochondral defect in rabbit. Cytotherapy. 2005 Jan 1;7(6):520-30.  [Google Scholar]

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