Does stem cell therapy for knee meniscus tears and post-meniscectomy work?
Ross Hauser, MD., Danielle R. Steilen-Matias, MMS, PA-C
Stem Cell therapy for knee meniscus tears and post-meniscectomy
This article will explore new research that paints a fascinating picture of natural meniscus healing, surgical and non-surgical meniscus repair, and when Stem Cell Therapy (Bone Marrow Aspirate Concentrate) may or may not work for your meniscus tear. We will also discuss the role of comprehensive Prolotherapy injections as a supportive treatment to stem cell therapy, not only in treating the meniscus but in the treatment and repair of the articular knee cartilage as well. If you are considering meniscus surgery or already had meniscus surgery, this article will hopefully provide some good information in the understanding of your injury and what to expect from the surgery, and what to expect from stem cell therapy.
The reality of stem cell therapy
- Stem cell therapy can be a valuable tool in helping people with chronic knee pain isolated on meniscus damage. We have seen excellent results in many patients with Bone Marrow Aspirate Concentrate. However, stem cell therapy needs to be understood within the reality of what this treatment can and cannot do and how this treatment should and should not be used.
We don’t treat everyone with stem cell therapy
- It is important to note that we do not use stem cell therapy on every patient. In fact, we use stem cell therapy in very few of our patients. We find that other simpler and less costly regenerative medicine injection treatments can work just as well. This is explained below.
Over expectation of what stem cell therapy can do may lead to patient disappointment
- In many people who reach out to our office, we find that they have an unrealistic expectation of what stem cell therapy can and cannot do. For some people, stem cell therapy cannot, in one simple injection, repair and reverse years of degenerative damage. Many treatments may be necessary. The patient should be aware of what stem cell therapy can really do.
- For example, stem cell therapy cannot generate a meniscus from nothing. If you do not have a meniscus, stem cell therapy as an injection will not make a new one. If you have a meniscus tear, lesion, or hole in cartilage, stem cell therapy may help create a natural healing patch, but, the treatment, like any medical treatment, has its limitations. Stem cell therapy can patch a hole, but without supportive treatments to address what caused the degenerative knee condition and what caused the hole in the cartilage in the first place, (knee instability and degenerative wear and tear motion from damaged and weakened knee ligaments), stem cell therapy will not be the single-shot cure a patient will hope for.
Stem cell for meniscus tears – what do people exploring stem cell therapy for their meniscus problems want to know about the treatment?
These are some of the questions we hope to provide insight into.
A male athlete in their early 30’s – I am not training nearly at the levels I use to.
Over the last 15 years, I have had multiple knee surgeries. I am missing, actually had removed, a large portion of my meniscus. This has lead to a thinning and wearing of the cartilage covering my femur and tibia. That is what my current MRI tells me. Yet I do not have any significant pain and I continue to run, cycle, and workout. But I had to significantly decrease the intensity and number of workouts. I am not training nearly at the levels I use to. I did have two bone marrow stem cell injections. They did not help. Can you help me understand why?
The answers will be discussed below.
The mid-50’s fitness instructor
I had an MRI a few months ago. I had/have degenerative wear and tear of my knee with a focus on the posterior horn medial meniscus. I work as a fitness instructor. My doctor recommended physical therapy twice a week times 6 weeks with a follow-up evaluation. The physical therapy did not help, I was told I need to get a “clean up,” arthroscopic surgery. I need to keep working and I am being told on the good side I will only be out for 6 weeks but I should prepare for 12 weeks. I heard stem cell therapy can help. Can it?
The research on stem cell therapy for meniscus tears. Does it work or not?
At our center, we have seen bone marrow aspirate stem cell therapy help many people. In support of our clinical observations is independent research. A reminder again. Stem cell therapy must be considered within the realistic expectation that it can help you achieve your treatment goals. It does not work for everyone. How would you know? A physical exam, motion ultrasound, and medical history review by a practice that has many years of experience helping people with meniscus tears would help you understand how this treatment could help you.
Research led by Rutgers University offered these observations about bone marrow aspirate concentrate stem cell therapy and meniscus injuries in the publication PM & R: The Journal of Injury, Function, and Rehabilitation. (1)
Here are the learning points:
- The meniscal tear treatment path traditionally begins with conservative measures such as physical therapy and referral for operative management for persistent or mechanical symptoms.
- If this treatment fails, it will lead to partial meniscectomy which is performed more than any other orthopedic procedure in the United States.
- This meniscal tear treatment, however, has shifted because recent literature has supported the attempt to preserve or repair the meniscus whenever possible given its importance for the structural integrity of the knee joint and the risk of early osteoarthritis associated with meniscus tissue is removed.
- There is a growing amount of evidence showing that elderly patients with complex meniscus tears and degenerative arthritis should not undergo arthroscopic surgery.
- Direct meniscus repair (suture) remains an option in ideal patients who are young and healthy and have tears near the more vascular periphery (where the blood circulation is) of the meniscus but it is not suitable for all patients.
- The use of orthobiologics such as platelet-rich plasma and mesenchymal stem cells have shown promise in augmenting surgical repairs or as standalone treatments, although research for their use in meniscal tear management is limited.
And in truth research is limited. However, as the research points out: “stem cells have shown promise in augmenting surgical repairs or as standalone treatments.”
For many, the meniscus can heal itself if you do not remove tissue. The healing elements in the meniscus and what they do, and what they cannot do if they are missing.
One of the often overlooked components of meniscus surgery is that it removes healing elements from the knee. Simply, meniscus surgery removes tissue, weakens the structure of the knee, leads to degeneration through instability and knee breakdown. In addition, surgery removes healing elements within the meniscus tissue that may help the knee naturally rebuild itself. Now there are people who have very successful knee surgeries for their meniscus problems. These are typically not the people we see in our office. We see people with disappointing surgical outcomes.
The healing elements: A brigade of natural native stem cells in the meniscus that move from the red zone to the white zone.
- In September 2017, in the Journal of Orthopaedic Research, (2) doctors at the University of Iowa, working with researchers from the Harvard Medical School and the National Institutes of Health, looked for the healing elements in the meniscus and identified what they do.
Let’s remember that these healing elements live in the meniscus. If you remove the meniscus, you reduce or remove the healing elements.
In this study, the researchers found that the meniscus has its own brigade of “stem cells” or chondrogenic progenitor cells (Chondrogenic = cartilage, progenitor = creator or originating cells) specifically in the blood-rich red zone of the meniscus. Further, the cells in the blood-rich zone could be called upon to migrate across the meniscus and appear at the site of a white zone (no blood supply portion of the meniscus) injury. (See our discussion red-zone and white-zone meniscus tears.)
- In essence, the injury is calling for help and the chondrogenic progenitor cells respond to begin the rebuilding process. The meniscus has its own damage control mechanism, it sits in the blood-rich portion of the meniscus. When the red zone meniscus is removed, the meniscus ability to heal itself is can be removed with it.
Research like this reaffirms two things:
- The meniscus does have the capability to repair and regenerate.
- When we surgically remove meniscus tissue we remove the cells that can naturally repair the meniscus damage.
So if the meniscus does have the capability to repair and regenerate with its own brigade of stem cells, why doesn’t it fix itself when it gets torn? Because the articular cartilage of the knee cannot hold the knee together long enough to let this happen.
This is a remarkably fascinating study on how a meniscus heals or does not heal. Researchers wanted to examine the meniscus healing process after an injury or surgical removal of meniscus tissue. In this animal study, the researchers removed a large portion of the meniscus in mice. (3)
What the doctors observed was the meniscus repair and regeneration process after the meniscectomy. After six weeks the doctors observed regenerated tissues resembled those of an intact meniscus forming. The bad news was the articular cartilage of the knee where the removed meniscus use to be. The cartilage significantly degenerated between two and four weeks after the surgical procedure, and subtle progression in cartilage degeneration was observed between 4 and 6 weeks.
The destructive cartilage/meniscus environment – This is why stem cell therapy can fail and it also explains why some people’s knees still hurt after surgery
- The suggestion is that the meniscus was trying to heal itself while the knee environment was collapsing towards degenerative disease. We have new meniscus tissue at 6 weeks being crushed by progressive degenerative changes. This is like trying to build a new house during an earthquake.
The researchers in this study performed a meniscectomy in the mice. This gives us an understanding of what happens in the knee after a meniscectomy.
- The left anterior halves of the medial menisci in mice were removed. Then the mice were observed to see how their knee dealt with this injury.
- On day three: Extensive macrophagic infiltration into the synovial membrane around the meniscectomized area was observed.
- Explanation: macrophages are immune cells that clean up and remove the debris left behind by injury. The body is removing hindrances to healing. In other words, the knee is getting ready to heal.
- On day three: Extensive macrophagic infiltration into the synovial membrane around the meniscectomized area was observed.
- Synovial hyperplasia was detected 2 weeks after the operation.
- Explanation: Synovial hyperplasia is inflammation. Healing inflammation. The synovial tissue of the knee was filled with many fibroblastic cells (collagen producers to rebuild cartilage).
- The articular cartilage at the interface of the resected meniscus significantly degenerated between 2 and 4 weeks after the surgical procedure, the subtle progression of cartilage degeneration was observed between 4 and 6 weeks. The degeneration slowed but continued.
In this study’s summation, the immune system’s rapid response to repair the knee, not only tries to regenerate meniscus tissue damaged by the surgery but also tried to reinforce and prevent damage to the articular cartilage of the knee as if the immune system knew that the meniscectomy would cause articular cartilage.
The researchers concluded that the remaining meniscus and the articular cartilage of the meniscectomized knee tried, in vain, to work together to regenerate the meniscus and protect the cartilage.
Harvard researchers see similar healing characteristics in a meniscus
Harvard researchers published in the medical journal Connective Tissue Research, (May 2017) found similar findings. They isolated and studied the native meniscal tissue in mice and also found an abundance of healing mechanisms. (4)
- The mouse meniscal stem cells had clonogenicity (the ability to survive in the hostile inflammatory environment and reproduce) and multi-potentiality (the ability to change and signal multiple types of healing mechanisms).
- They had the ability to create important extracellular matrix components of an adult meniscus. Please see my article on extracellular matrix and joint healing for fascinating new research.
Stem Cell Therapy for meniscus damage – is there validity to the treatment?
In the above research, we are suggesting that there are native stem cells in a knee, specifically, the meniscus is trying to repair. Red zone stem cells move to the white zone to help with repair, cartilage stem cells and meniscus stem cells are trying to work together to fix a bone-on-bone situation, the knee is always trying to heal. The problem is that there is too much damage and there is too much knee instability causing unnatural and destructive motion in the knee. The repair cannot hold. And again, this is why stem cell injections for a meniscus tear may not work. Stem cell therapy is trying to patch a hole while the whole knee is crumbling around it.
October 2020 research: Bone marrow-derived mesenchymal stem cells have the potential to help form meniscus tissue
An October 2020 study (5) lead by the University of Alberta in Edmonton, Canada offered this observation in the journal Tissue Engineering (Part A). “Bone marrow-derived mesenchymal stem cells have the potential to form the mechanically responsive matrices of joint tissues, including the menisci of the knee joint.” Matrices are the scaffold-like structures that are created in the body for things like fingernails and cartilage to grow on.
In this study a comparison was made: Do bone marrow stem cells taken from the iliac crest (the wing of the pelvis) create meniscus matrices? Further, if they do, how do they compare with stem cells taken from meniscus fibrochondrocytes cells (cartilage cells) taken from meniscus tissue removed during a partial meniscectomy of non-osteoarthritic knees. The general results? Bone marrow-derived mesenchymal stem cells from the iliac crest produced better meniscus building block tissue better than meniscus tissue did.
So if bone marrow-derived stem cells can jump-start the regrowth and rebuilding of meniscus tissue, how does the treatment fail?
An injury to the meniscus is an injury to the entire knee joint. If you do not figure out the whole knee joint, stem cell therapy for a meniscus tear will fail.
An international team of researchers writing in the journal Sports Medicine offers a summary of their research that should be of great interest to the patient athlete researching stem cells for meniscus repair. (6)
- “Regenerative medicine (stem cells, Prolotherapy, and blood platelet solutions) seeks to harness the potential of cell biology for tissue replacement therapies, which will restore lost tissue functionality. Controlling and enhancing tissue healing is not just a matter of cells, but also of molecules and mechanical forces.”
- My note: Stem cell treatments are much more than simply injecting stem cells into the knee – while there are no guarantees that any treatment will work 100% – we, as doctors, have to make sure we are doing the most we can to guarantee success. This includes an understanding that an athlete may have had a long history of painkiller and cortisone use – this is explained in our article How stem cells heal degenerative joint disease after years of cortisone and painkillers
- This is also covered in our article Why didn’t stem cell therapy work for my knee pain? Where we describe stem cell therapy failure because a single injection does not treat the whole knee. Meniscus damage is a whole knee disease as outlined in the research above.
- Continuing the research cited above from the journal Sports Medicine: The researchers acknowledge the following problems with consistency in treatment. First they “describe the main biological technologies to boost musculoskeletal healing, including bone marrow and subcutaneous fat-derived regenerative products, as well as platelet-rich plasma and conditioned media (meniscus scaffolds).”
- Then they examined a total of 54 studies that investigated the effects of mesenchymal stem-cell products for joint conditions including anterior cruciate ligament, meniscus, and chondral lesions as well as osteoarthritis. In 22 studies, cellular products were injected intra-articularly, whereas in 32 studies mesenchymal stem-cell products were implanted during surgical/arthroscopic procedures. The heterogeneity of clinical conditions, cellular products, and approaches for delivery/implantation make comparability difficult.
- Mesenchymal stem-cell products appear safe in the short- and mid-term, but studies with a long follow-up are scarce. Although the current number of randomized clinical studies is low, stem-cell products may have therapeutic potential. However, these regenerative technologies still need to be optimized.”
What are we seeing in the illustration below?
We are seeing photographs from a medical research paper published in 2012 titled: “Effects of intra-articular administration of autologous bone marrow aspirate on the healing of full-thickness meniscal tear: an experimental study on sheep.” (7)
- The series of photos demonstrate that: “An injection of bone marrow into the meniscus tear site improves healing in a meniscal tear model as demonstrated by both light and electron microscopic findings.”
- In picture 2 we see an increase in synovial tissue (the protective membrane that creates synovial fluid) and vascularization (increase blood circulation) in the meniscus tissue treated with bone marrow aspirate.
- Picture 3 demonstrates healing in the meniscus at 16 weeks
- Picture 6 demonstrates granulation tissue (new connective tissue and the microvessels that supply blood to it.)
- Picture 8 within the meniscus tear is the development of cartilage cells.
To be clear, this set of images demonstrate the healing mechanism in an experimental model of bone marrow aspirate or stem cell therapy. It is an insight into how the procedure can help some people.
Building on this research a May 2018 study (8) from the Regenerative Engineering Laboratory Columbia University Medical Center noted further on the ability of stem cells to heal meniscus tears in experimental studies. Here is what they wrote:
“Upon injury, the outer zone of the meniscus can be repaired and expected to functionally heal but tears in the inner avascular region are unlikely to heal. To date, (May 2018) no regenerative therapy has been proven successful for consistently promoting healing in inner-zone meniscus tears. Here, we show that controlled applications of connective tissue growth factor (CTGF) and transforming growth factor-beta 3 (TGFβ3) can induce seamless healing of avascular meniscus tears by inducing recruitment and step-wise differentiation of synovial mesenchymal stem/progenitor cells (syMSCs).”
Let’s put that in simpler terms
- transforming growth factor-beta 3 helps regulate cell differentiation. If you have been researching stem cell therapy you will recognize “cell differentiation” as an important point in the rebuilding process. Cell differentiation is the ability of stem cells to differentiate or change into building blocks of cartilage or connective tissue.
An explanation of the role of connective tissue growth factor is offered in research from the University of Oklahoma Health Sciences Center published in December 2017. (9)
“Connective tissue growth factor is a matricellular (the matrice – the importance of which is mentioned above) protein expressed in the vascular wall, which regulates diverse cellular functions including cell adhesion (cells stick together so they can form complex tissue), matrix production (the scaffold to build repair – please see our article The Extracellular matrix (ECM). How comprehensive prolotherapy repairs cartilage,) structural remodeling (cells are remodeled and repurposed), angiogenesis (blood flow and circulation through the production of new blood vessels), and cell proliferation and differentiation.”
So what does all this mean?
In the simplest of terms, stem cell therapy, specifically bone marrow aspirate can help rebuild meniscus tears across the meniscus from the red to white zone. In laboratory and experimental studies. But what about inside your knee?
Bone marrow aspirate – stem cell therapy and Prolotherapy
In our article, The different types of knee injections, we show research and clinical outcomes in comparing the many different types of knee injections.
As pointed out at the onset of this article, stem cell therapy brings a lot of confusion to patients. There are many different types of stem cells. Please refer to this article Amniotic, cord blood, placenta stem cell therapy.
In research published by the Journal of Bone and Joint Surgery, (10) doctors have found that a single stem cell injection following meniscus knee surgery may provide knee pain relief and aid in meniscus regrowth. In this study, patients received a single injection of donated adult stem cells following the surgical removal of all or part of a torn meniscus. These patients reported a significant reduction in pain. Further, some meniscal tissue regrew. Up to 15 percent increase in meniscal volume at one year. There was no additional increase in meniscal volume at year two.
That question was seemingly answered in an accompanying press release from the American Academy of Orthopaedic Surgeons’ press department.
“The results of this study suggest that mesenchymal stem cells have the potential to improve the overall condition of the knee joint,” said Dr. Vangsness (a study author). “I am very excited and encouraged” by the results. With the success of a single injection, “It begs the question: What if we give a series of injections?” (11)
In our office, “Bone marrow aspirate” or stem cell therapy is used in conjunction with dextrose Prolotherapy. Prolotherapy is a non-surgical regenerative treatment that can stimulate natural healing repair in the knee. The goal of the treatment to rebuild tissue and provide stability to the knee. Stem cell therapy or Stem cell Prolotherapy is the combined use of your own harvested stem cells and dextrose Prolotherapy to treat the entire knee environment.
Not all meniscus tears and injuries (even those after meniscus surgery) require stem cell therapy to heal. We have documented in numerous studies that simple dextrose Prolotherapy has a 90% success rate in our office. However, for cases of the more advanced meniscus and related cartilage damage, our team of Prolotherapy practitioners may choose to use stem cell injections in combination with dextrose Prolotherapy to strengthen and stabilize the surrounding support structures of the knee.
Stem cells, combined with Platelet Rich Plasma Therapy meniscus injections and Prolotherapy meniscus injections are healing solutions. Caring Medical has conducted research showing the effectiveness of PRP Prolotherapy (PRPP), including case reports of MRI-documented meniscus tears successfully treated with Prolotherapy and Platelet Rich Plasma. (12)
- Bone marrow stem cell therapy and Prolotherapy | Published review 7 case histories
- Bone Marrow Aspirate Prolotherapy for knee pain
1 Chirichella PS, Jow S, Iacono S, Wey HE, Malanga GA. Treatment of Knee Meniscus Pathology: Rehabilitation, Surgery, and Orthobiologics. PM&R. 2018 Sep 7. [Google Scholar]
2. Seol D, Zhou C, Brouillette MJ, Song I, Yu Y, Choe HH, Lehman AD, Jang KW, Fredericks DC, Laughlin BJ, Martin JA. Characteristics of meniscus progenitor cells migrated from injured meniscus. Journal of Orthopaedic Research. 2016 Nov 1. [Google Scholar]
3. Hiyama K, Muneta T, Koga H, Sekiya I, Tsuji K. Meniscal regeneration after resection of the anterior half of the medial meniscus in mice. Journal of Orthopaedic Research. 2016 Nov 2. [Google Scholar]
4 Gamer LW, Shi RR, Gendelman A, Mathewson D, Gamer J, Rosen V. Identification and characterization of adult mouse meniscus stem/progenitor cells. Connective tissue research. 2017 Feb 4:1-8. [Google Scholar]
5 Elkhenany HA, Szojka ARA, Mulet-Sierra A, Liang Y, Kunze M, Lan X, Sommerfeldt M, Jomha NM, Adesida AB. Bone Marrow Mesenchymal Stem Cell-Derived Tissues are Mechanically Superior to Meniscus Cells. Tissue Eng Part A. 2020 Oct 30. [Google Scholar].
6 Andia I, Maffulli N. Biological therapies in regenerative sports medicine. Sports Medicine. 2017 May 1;47(5):807-28. [Google Scholar]
7 Duygulu F, Demirel M, Atalan G, Kaymaz FF, Kocabey Y, Dulgeroglu TC, Candemir H. Effects of intra-articular administration of autologous bone marrow aspirate on healing of full-thickness meniscal tear: an experimental study on sheep. [Google Scholar]
8 Tarafder S, Gulko J, Sim KH, Yang J, Cook JL, Lee CH. Engineered healing of avascular meniscus tears by stem cell recruitment. Scientific reports. 2018 May 25;8(1):1-9. [Google Scholar]
9 Ungvari Z, Valcarcel-Ares MN, Tarantini S, Yabluchanskiy A, Fülöp GA, Kiss T, Csiszar A. Connective tissue growth factor (CTGF) in age-related vascular pathologies. Geroscience. 2017 Dec 1;39(5-6):491-8. [Google Scholar]
10 Vangsness Jr CT, Jack Farr II, Boyd J, Dellaero DT, Mills CR, LeRoux-Williams M. Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study. JBJS. 2014 Jan 15;96(2):90-8. [Google Scholar]
11 Stem Cell therapy following Meniscal Surgery http://newsroom.aaos.org/media-resources/Press-releases/stem-cell-therapy-following-meniscus-knee-surgery-may-reduce-pain-restore-meniscus.htm
12 Hauser R, Phillips HJ, Maddela HS. The case for utilizing Prolotherapy as first-line treatment for meniscal pathology: a retrospective study shows Prolotherapy is effective in the treatment of MRI-documented meniscal tears and degeneration. Journal of Prolotherapy. 2010;2(3):416-437. [Google Scholar]