Does stem cell therapy regrow cartilage?

Ross Hauser, MD

In this article, we will examine the research and the clinical application of stem cell therapy for articular cartilage repair.

Case Histories: Bone marrow stem cell therapy in patients with knee and hip osteoarthritis

Stem cell therapy can be confusing to many patients because there are many services being offered as stem cell therapy. The most common are:

Both of these treatments are stem cells from you.

There are also stem cell therapies that are not really stem cell therapies. These are:

Many emails that come into our office ask us to compare the various forms of stem cell therapies. We have a very extensive series of articles discussing the different types of injections for knee pain. You can see that article here: The different types of knee injections. In addition to stem cell therapy, we talk about cortisone, Hyaluronic acid injections, Platelet Rich Plasma Therapy, Botox injections into the knee, and ozone therapy

Young stem cells versus old stem cells

Most of the emails we get are from people who have recently attended a seminar or a webinar in which they were introduced to the idea that a newborn baby was willing to donate his/her amniotic fluid or cord blood or placenta afterbirth material to them to replace the patients own old or weakened stem cells. The use of this donated material is not stem cell therapy as there has not been shown by any credible research that there are actual live stem cells in the treatment. This is discussed further in our article on “amniotic stem cell therapy.” So while these treatments may help some people, and we have seen people who responded positively to these injections, no matter what is in them, we will concentrate this article on bone marrow aspirate concentrate or as we call it bone marrow Prolotherapy. This treatment refers to the use of bone marrow concentrate injections into areas of degenerative joint disease to stop and repair degenerative changes. The use of bone marrow aspirate relies on the action of stem cells to initiate and guide this joint repair.

Mayo Clinic and Yale University studies on your own bone marrow stem cells

Doctors at the Mayo Clinic and Yale University published their research on the benefits of Bone Marrow Aspirate Concentrate for Knee Osteoarthritis in the American Journal of Sports Medicine(1) Here is the summary of that research:

In their single-blind, placebo-controlled trial, 25 patients with bilateral knee pain from bilateral knee osteoarthritis were randomized to receive Bone marrow aspirate concentrate into one knee and saline placebo into the other.

“The current literature demonstrates the potential benefits of utilizing concentrated bone marrow aspirate.”

Doctors in New Jersey at the Department of Orthopedic Surgery, Jersey City Medical Center published their findings in support of this research, in the World Journal of Orthopedics,(2) here is what the paper said:

“The current literature demonstrates the potential benefits of utilizing concentrated bone marrow aspirate for the repair of cartilaginous lesions, bony defects, and tendon injuries in the clinical setting.

The studies have demonstrated using concentrated bone marrow aspirate as an adjunctive procedure can result in cartilage healing similar to that of native hyaline tissuefaster time to bony unionand a lower rate of tendon re-rupture.”

In a 2015 study, (3which is heavily cited by other research papers, doctors announced their findings in patients who received bone marrow stem cell therapy in the hip, knee, and ankle for treatments of osteoarthritis. All seventeen patients in the study exhibited therapeutic benefits such as increased walking distance, increased function, and reduced pain.”

Doctors publishing in the Journal of Clinical Orthopaedics and Trauma (4cited this research among others in saying

Doctors at Georgia Regents University wrote in the Clinical and Translational Medicine (5in support of the above research:

What are Bone marrow concentrate injections?

Direct Bone Marrow Injection

Using stem cells taken from a patient’s bone marrow is becoming a therapy of interest due to the potential of these mesenchymal stem cells to differentiate into other types of cells such as bone and cartilage.

Bone Marrow is the liquid spongy-type tissue found in the hallow (interior) of bones. It is primarily a fatty tissue that houses stem cells that are responsible for the formation of other cells. These mesenchymal stem cells (MSC), also called marrow stromal cells, can differentiate (change) into a variety of cell types including osteoblasts (bone cells)chondrocytes (cartilage cells), myocytes (muscle cells), adipocytes (fat), fibroblasts (ligament and tendon) and others when reintroduced into the body by injection. Bone marrow also contains hematopoietic stem cells that give rise to the white and red blood cells and platelets.

Stem cell therapy is a controversial treatment. In some instances, unrealistic expectations and claims may be made in how beneficial this treatment can be. Stem cell therapy does help many people. It does not help everyone. Please see our articles:

In our office, we focus on bone marrow aspirate or “bone marrow stem cell therapy.” This is will be discussed below.

I am “bone on bone.” “My mom is bone on bone.” “My dad is bone on bone.”

The predominant number of emails we get are from someone who has bone on bone knee or bone on bone hip, or, their aging parents are in a lot of pain and they do not want them to go through the joint replacement surgery. The obvious goal of the treatment that these people or the adult children of aging parents is the avoidance of a knee replacement or hip replacement by growing back the “missing” cartilage.

These are the questions we get:

My 78-year-old mother

In these types of questions, we do an initial screening to make a realistic assessment of who stem cell therapy can and cannot help. Stem Cell therapy can help someone who has some normal range of motion in their knee or hip or shoulder.

What are we seeing in this image?

At our center, we use different types of regenerative medicine injections to help restore and repair damaged joints. Not everyone is a good candidate for treatment and in these cases, they would be advised to continue with the possibility of joint replacement. In other cases, because of pre-existing medical conditions or other factors that make surgery impossible, we tell the patients of the realistic expectation of how much these treatments can help.

While this article focuses on stem cell therapy we use the same guidelines in discussing the realistic expectation that Prolotherapy injections with simple dextrose will help as stem cell therapy or Platelet Rich Plasma injections.

In this image, we see a poor candidate’s hip. What makes them a poor candidate? They have severe degeneration of the right hip. They have lost all the joint space and have developed bone spurs throughout the hip. This patient had severely limited range of motion and was unable to flex or bend the hip to 90 degrees or internally rotate it at all. Due to these factors, this patient was rated as a poor candidate for injection treatment.

In this image we see a poor candidate's hip. What makes them a poor candidate? They have severe degeneration of the right hip. They have lost all the joint space and have developed bone spurs throughout the hip. This patient had severely limited range of motion and was unable to flex or bend the hip to 90 degrees or internally rotate it at all. Due to these factors this patients was rated as a poor candidate for injection treatment.

What are we seeing in this image?

On the scale of poor-fair-good-excellent candidates for treatment, this knee was assessed as a fair candidate for treatment. The reason is that this person had lost nearly all her cartilage at the outer edge of the knee. She also had a limited range of motion on physical examination. She did however have a successful treatment that helped improve her quality of life. This is not the case for all fair candidates but successful treatment is usually for typical treatment that fails.

In the scale of poor-fair-good-excellent candidates for treatment this knee was assessed as a fair candidate for treatment. The reason is that this person had lost nearly all her cartilage at the outer edge of the knee. She also had a limited range of motion on physical examination.

What are we seeing in this image?

On the scale of poor-fair-good-excellent candidates for treatment, this shoulder was assessed as a good candidate for treatment. The reason is that this shoulder has maintained a good overall architecture. Simple this means that this shoulder still looks like a shoulder. Degenerative shoulder disease and bone spurs have not altered the shoulder’s natural appearance or function, yet. Most importantly, even with pain, the patient had a full range of motion in their shoulder.

In the scale of poor-fair-good-excellent candidates for treatment this shoulder was assessed as a good candidate for treatment. The reason is that this shoulder has maintained a good overall architecture. Simple this means that this shoulder still looks like a shoulder. Degenerative shoulder disease and bone spurs have not altered the shoulder's natural appearance or function, yet. Most importantly, even with pain, the patient had a full range of motion in their shoulder. 

Does stem cell therapy regrow cartilage?

So let’s now return to the original question. Does stem cell therapy regrow cartilage? The answer is yes, but we must have a realistic expectation of how much, how fast, and how effective this can be. The treatment will not work for everyone with poor candidates having a less than likely successful outcome.

How does stem cell therapy regrow cartilage? Researchers are not sure.

In early 2017, doctors writing in the medical journal Stem Cells International (6) 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.”

What does all this mean? 

July 2020 (7) built on this research to suggest: “Full-thickness cartilage defects if left alone would increase the risk of osteoarthritis with severe associated pain and functional disability.  . . The capability of the mesenchymal stem cells to repair and regenerate cartilage has been widely investigated. . .Several studies have demonstrated promising results in the clinical application for repair of chondral defects as an adjuvant (during surgery in some cases) or independent procedure. Intra-articular (mesenchymal stem cells (MSCs)  provide improvements in pain and function in knee osteoarthritis at short-term follow-up in many studies.

The Conclusion of this paper: “Some efficacy has been shown of mesenchymal stem cells (MSCs) for cartilage repair in osteoarthritis; however, the evidence of the efficacy of intra-articular MSCs on both clinical outcomes and cartilage repair remains limited. Despite the high quality of evidence to support, MSC therapy has emerged but further refinement of methodology will be necessary to support its routine clinical use.”

In other words: It works for many people, not all, there needs to be a refinement in the treatment’s application to make it more successful for more people.

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 (8) 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.

In 2014, Dr. Shinya Yamasaki who lead the above-cited 1994 study twenty years earlier, lead another study, (9) 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.

In a heavily cited 2003 study (10) from Osiris Therapeutics in Baltimore, doctors reported significant improvement in the 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 the osteoarthritic disease was reduced in MSC-treated joints compared with controls.

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.

Our Research: Caring Medical published studies

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. (11)

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

In this study, we suggested that to make stem cell therapy’s ability to regrow cartilage more effective, a supportive treatment, Prolotherapy, injections of simple dextrose, should be considered. This is explained further below and demonstrated in the videos of this article. In our paper we noted:

This was a case history study. These are the cases we presented:

Right ankle pain – Stem Cell Treatment alone

Case 1: A 59-year-old female with a history of three years of right ankle pain. The patient was unable to walk more than 30 feet without severe ankle pain and had to stop all weight-bearing recreational activities. Cortisone therapy had been unsuccessful and ankle fusion had been recommended. Based on X-ray and MRI findings, the patient was diagnosed with osteoarthritis, avascular necrosis of the talus, and synovitis.

Pain in Both Knees – Stem Cell Treatment alone

Case 2: A 69-year-old male with pain in both knees. In his left knee, he reported pain of 4/10 and a 30% frequency of what that pain occurred. His right knee was worse. He reported a 7/10 pain scale and a 90% frequency. The pain almost all the time.

Pain in Both Hips – Stem Cell Treatment alone

Case 3: A 76-year-old woman with pain in both hips. Worse on the left side. She was unable to walk more than a mile without significant pain. The patient had received a recommendation for hip replacement.

Pain in Both Knees and Right Hip – Stem Cell Treatment alone

Case 4: A 56-year-old female had pain in both knees and right hip. The pain was severe in the right knee, with frequent crepitus (cracking, crunching) and instability, and had forced the patient to discontinue running.

Case presentations: Stem Cell Therapy and Prolotherapy combined

Case 5: A 56-year-old man with bilateral knee pain. 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.

Case 6: A 69-year-old female came into our office with pain in both knees.

She had been previously diagnosed with osteoarthritis, had arthroscopic surgery to both knees eight years earlier, and medial meniscus repair in both knees 15 years earlier.

The patient reported 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.

The patient received six treatments in both knees with dextrose prolotherapy over a ten-month period.

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/dextrose treatments, five months apart.

Case 7: A 63-year-old male came into our office with pain in both hips.

The patient received five treatments with dextrose prolotherapy in both hips over a period of 5 months. During this period, the patient reported an overall improvement of 50%; however, this reduced to 30%–40% at the conclusion of the treatment period, at which time pain intensity was 6/10 increased but with less frequency.

Crepitus, previously absent, was now marked. At this point, the patient began a series of two bone marrow stem cell injection/dextrose treatments two months apart.

At the time of the second treatment, pain intensity reduced. Crepitus was reduced. Specific pain manifestations previously noted, including ischial tuberosity pain and lateral hip pain, had abated, and the patient reported being able to walk without a cane for the first time in years.

Two months after the second bone marrow stem cell injection/dextrose treatments, pain intensity was 1/10 with a frequency of 10%. The patient reported walking without a limp and no longer needing a cane.

More research: 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. (13)

14 Hauser R, Woldin B. Treating osteoarthritic joints using dextrose prolotherapy and direct bone marrow aspirate injection therapy. The Open Arthritis Journal. 2013 Dec 13;7(1).

Results: Patient-reported improvements in pain relief and joint function were statistically significant, as well as 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 bone marrow aspirate has the potential for enhancing the quality of life of individuals with the disease. Read full article

Dextrose and stem cells

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. (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 gains in pain relief and functionality. Read Full Article

Highlights of this study:

We are going to bring in research and an important published paper from Purdue University to help understand and confirm the notion that dextrose, especially hypertonic (extra) dextrose is a significant factor in the ability of mesenchymal stem cells from bone marrow to proliferate. (15)

Simply, the researchers took stem cells and glucose and put them in an experimental situation. The experiment was to see how varying levels of glucose affected stem cell numbers (proliferation).  What the experiment found was that mesenchymal stem cell consumption of glucose increased proportionally with the glucose concentration in the medium. The more glucose, the more the stem cells ate, the more the stem cells multiplied.

In summary, hypertonic dextrose in published studies helps stem cell proliferation in vitro (in cultures.)  While this is important, more important is what it does in the human body.  We have written numerous studies on hypertonic dextrose Prolotherapy and stem cells and feel the results speak for themselves.

Questions about our treatments?

If you have questions about your joint pain and how we may be able to help you, please contact us and get help and information from our Caring Medical staff.

This is a picture of Ross Hauser, MD, Danielle Steilen-Matias, PA-C, Brian Hutcheson, DC. They treat people with non-surgical regenerative medicine injections. Offices are located in Oak Park, Illinois and Fort Myers, Florida.

Brian Hutcheson, DC | Ross Hauser, MD | Danielle Steilen-Matias, PA-C

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References

1 Shapiro SA, Kazmerchak SE, Heckman MG, Zubair AC, O’Connor MI. A Prospective, Single-Blind, Placebo-Controlled Trial of Bone Marrow Aspirate Concentrate for Knee Osteoarthritis. Am J Sports Med. 2017 Jan;45(1):82-90. doi: 10.1177/0363546516662455. Epub 2016 Sep 30. [Google Scholar]
2 Gianakos AL, Sun L, Patel JN, Adams DM, Liporace FA. Clinical application of concentrated bone marrow aspirate in orthopaedics: A systematic review. World journal of orthopedics. 2017 Jun 18;8(6):491.  [Google Scholar]
Emadedin M, Ghorbani Liastani M, Fazeli R, Mohseni F, et al. Long-Term Follow-up of Intra-articular Injection of Autologous Mesenchymal Stem Cells in Patients with Knee, Ankle, or Hip Osteoarthritis. Arch Iran Med. 2015 Jun;18(6):336-44. doi: 015186/AIM.003.  [Google Scholar]
4 Afizah H, Hui JH. Mesenchymal stem cell therapy for osteoarthritis. Journal of clinical orthopaedics and trauma. 2016 Sep 30;7(3):177-82.  [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 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]
7 Debnath UK. Mesenchymal Stem Cell Therapy in Chondral Defects of Knee: Current Concept Review. Indian Journal of Orthopaedics. 2020 Jul 27:1-9. [Google Scholar]
8 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]
9 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]
10 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]
11 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]
12 Hauser R, Woldin B. Treating osteoarthritic joints using dextrose prolotherapy and direct bone marrow aspirate injection therapy. The Open Arthritis Journal. 2013 Dec 13;7(1).
13 Hauser RA, Eteshola E. Rationale for using direct bone marrow aspirate as a proliferant for regenerative injection therapy (prolotherapy). The Open Stem Cell Journal. 2013 Dec 13;4(1). [Google Scholar]
14 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 [Google Scholar]

 

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