Marc Darrow MD,JD

Many people today are exploring meniscus surgery alternatives. One reason is that they may still be on a waiting list to get the surgery and have somehow managed to “live with it.” Another is that they have been doing research and are not absolutely convinced that meniscus surgery will help them anyway.

Is surgery the only option? What is the future of meniscus repair treatments? According to a March 2021 study (1) the future of meniscus repair treatments is not only surgery. It is suggested that that orthobiologics (PRP and stem cell therapy) should play an important role in meniscus repair.

This study was the cumulative result of an electronic survey including 10 questions sent in a blind fashion to the faculty members of the 5th International Conference on Meniscus Science and Surgery. The responders of this study suggested that the future of meniscus science should be focused on meniscal preservation techniques through meniscus repair, addressing meniscal extrusion, and the use of orthobiologics.

Failed Meniscus Surgery is something we often see.

Someone will write us that they suffered a bucket handle meniscus tear and attempted to repair it. They will write about two or even three or meniscus surgeries that failed and then a subsequent total meniscectomy after they continued to try to “play through the meniscus problem.”

Others write that they have put off meniscus surgery for various reasons, Eventually their meniscus injury has become much worse and even though their pain has increased they are still looking for options to knee arthroscopic surgery.

Others have been given the ultimatum that not only do they need knee surgery now, they need total knee replacement because their meniscus is shredded, their knee is now bone-on-bone, and there are no other options left.

A July 2021 study (2) examined the effectiveness of arthroscopic partial meniscectomy by reviewing six previously published studies. In all six reviews of randomized controlled trials, arthroscopic partial meniscectomy did not show clinically important benefit over conservative treatment for knee function and pain. One of the studies which examined 140 middle aged patients with degenerative meniscal tears, arthroscopic partial meniscectomy provided no clinically relevant difference in Knee Injury and Osteoarthritis Outcome Score compared with a 12 week supervised exercise program.

The knee needs its meniscus: 

A summary of the role of the meniscus is given in a June 2021 paper (3) exploring the use of Platelet rich Plasma injections after meniscus surgery and whether the injections facilitated a faster healing. I will discuss that further below.

“The meniscus plays an important role in the knee joint, as it plays a role in shock absorption and transmission, joint stabilization, proprioception, lubrication and nutrition of the articular cartilage. Biomechanical studies have shown that a loss of meniscal integrity leads to changes in kinematics and loading of the knee joint. Even a loss of only 15–34% of the meniscus tissue increases the load on the hyaline cartilage by up to 350%.”

In this image we are look down at the top of the knee and seeing what sits on top of the shin bone. On this knee’s right side is the medical collateral ligament next to the medical meniscus. To this knee’s left is the lateral meniscus and next to it is the lateral collateral ligament. We also see the red and white zones.

Meniscus repair surgery research notes: “in the knees without the meniscus, the impact and load are three times higher.”

A 2020 study in The archives of bone and joint surgery (4) offers an updated opinion on meniscus surgery. Here are some points brought up by the surgeon researchers.

The knee needs its meniscus:

  • “The menisci (meniscus) perform many essential biomechanical functions. These functions include load transmission, shock absorption, stability, nutrition, joint lubrication, and proprioception (the sense of knee in 3D space). They also serve to decrease contact stress and increase contact area and joint congruency. The knee would be deprived of all these functions if the meniscus removed. Therefore, in the knees without the meniscus, the impact and load are three times higher.”

Surgical repair? Patients should be warned the return to sport should be delayed for up to 6 months

  • “Rehabilitation after meniscal repair is slower and different from rehabilitation after meniscectomy. The physiotherapist and surgeon should respect the slow process of biological healing of the meniscus and therefore they need to be careful with the rehabilitation program especially in active flexion. The return to sport should be delayed for up to 6 months; however, 86 to 91% of patients could back to play. It is also crucial for the patient to know there is 8 to 20% risk of failure and re-operation, however, the long term outcome of meniscal repair is better than partial meniscectomy because of chondroprotective action of meniscus.”

Meniscus repair is not a small surgery without complication.

  • “Meniscus repair is not a small surgery without complication. It is technically challenging and has a steep learning curve. General complications of arthroscopy such as venous thromboembolism, infection and vascular injury could occur. Specific complication including nerve injuries, ligamentous injury, iatrogenic cartilage lesions, and poor suture techniques can happen during meniscal repair. The surgeon should depict and accept the eventual complications and address them as rapidly as possible. It is also important to form patients about potential complications.”

Failure of meniscal repair occur in up to 25 % of patients

  • “Failure of meniscal repair occur in up to 25 % of patients. Failures in the first six months of surgery are usually related to technical issues during repair, while failures between 6 and 24 months are indicating poor healing process. Failure later than 2 years of repair show retear or degenerative processes in the meniscus. . . Secondary meniscectomy is a treatment for failed meniscal repair. The amount of meniscal resection is less in 35% of cases, which shows partial healing of the meniscus. Revision of meniscal repair is another option and two small series reported 25 to 33% failure rate for the procedure.”

In this illustration we see the various types of meniscus repairs and meniscus tears.

In the box below we see various meniscus tear progressions:

  • A small meniscus radial tear to a large meniscus radial tear which then progresses to a meniscus flap tear which then progresses to a complex or degenerative meniscus tear.
  • We also see:
    • A Double flap tear
    • Discoid Meniscus
    • Peripheral Tear
    • Horizontal Flap Tear
    • Displaced Flap Tear


Meniscus transplant surgery – “Meniscal allograft transplantation for symptomatic knees after meniscectomy decreases pain and often improves function, but it does not replicate a normal meniscus”

Sometimes I will get an email or phone call asking me about meniscus transplants. The person who asks me has been told that they have a bone on bone situation in their knee. What I find interesting is that many of these people are active people. They maybe having a little trouble running or jogging but they can ride their bicycles without issue, they are even skiing, and they can walk okay. So this is a knee that is functioning and moving. But, the person who contacts me says that they have be recommended to a meniscus transplant because they have “bone on bone and the meniscus transplant will bring back some cushion.”

Meniscal transplant is a very major surgery.

In December 2020, there was an editorial in the medical journal Arthroscopy (5). It gives a good reality of the meniscus transplant outcome.

“Meniscal allograft transplantation for symptomatic knees after meniscectomy decreases pain and often improves function, but it does not replicate a normal meniscus. The ability of to delay arthritic changes is an ongoing area of study, and it is known that outcomes and graft survivorship deteriorate with longer follow-up. Recommended indications are symptomatic patients after meniscectomy with mild (or at most moderate) degenerative changes and absence of (or surgically corrected) associated malalignment or ligament deficiency. When these indications are followed, 80% of patients improve, with survivorship of 83% at 10 years and 56.2% at 20 years.

Can stem cell therapy regenerate meniscus tissue?

For many people, the long rehabilitation, possible need for secondary surgery, and other post-surgical factors weigh heavily in their decision making process as to how to proceed to fix their meniscus tear. For many people, regenerative medicine in the form of stem cell therapy may be something to be explored.

Let’s look at an October 2020 study (6) that made some interesting observations. What the research team wanted to do was assess Bone marrow-derived mesenchymal stem cells’ potential to engineer meniscus-like tissue. The researchers pointed out that “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.” So to test how good these stem cells were at re-engineering meniscus tissue, they compared the bone marrow stem cells taken from the iliac crest versus the meniscus fibrochondrocytes cells (cartilage cells) isolated from castoffs of partial meniscectomy from non-osteoarthritic knees.

To simulate conditions that may occur in the human body after cell transplantation, the bone marrow-derived mesenchymal stem cells were cultured in type I collagen (the stuff that cartilage is made of) scaffolds. What they found was that the bone marrow-derived mesenchymal stem cells produced functional replacement meniscus tissue better than meniscus tissue did.

This study is not definitive in the way bone marrow derived stem cells may heal and regenerate meniscus tissue. What it does show however is what could be possible in the right setting.

The Meniscus is always trying to make more meniscus

A study in the Journal of orthopaedic research (7) lead by the Department of Orthopaedics and Rehabilitation, University of Iowa discusses how a meniscus regenerates and heals.

The researchers of this study hypothesized that the meniscus contains a population of regenerative cells, (cells that stimulate stem cell activity) and that these cells migrate to the site of meniscal injury.

“White Zone,” and “Red Zone,”

In a recent study, doctors noted: “The repair of meniscus tissue in the avascular zone (the White Zone) remains a great challenge, largely owing to their limited healing capacity (Or the lack of blood supply, that is why the zone is white).” The researchers continued: ” A comprehensive review of the literature suggests that MSCs possess an intrinsic therapeutic potential that can directly and indirectly contribute to meniscus healing.”(8)

If you had a meniscus tear you are familiar with “White Zone,” and “Red Zone,” meniscus tears. The “Red Zone,” part of the meniscus, the outer edges, receives a steady stream of healing cells from its well organized blood vessel network. For those of you with a meniscus injury that is being recommended to surgery, you may have had your doctor explain to you that you have a “White Zone,” tear. The “White Zone,” lies in the center of the meniscus. It does not have a well organized blood network. It is these meniscal injuries that send patients to surgery.

This is what these researchers said: “studies revealed that migrating cells were mainly confined to the red zone in normal menisci: (This is the area where the meniscus has good blood flow and healing elements are abundant). However, these cells were capable of repopulating defects made in the white zone, (the area without circulation). When the meniscus was injured, migrating cell numbers increased dramatically. Stem cells in the knee increased in number to combat the injury. These findings demonstrate that, much as in articular cartilage, injuries to the meniscus mobilize an intrinsic progenitor cell population with strong reparative potential, even into the white zone area.”

The meniscus is mobilizing the stem cells already in the knee to the site of the its injury.

Stem cell numbers? What some may find fascinating is that the meniscus signals for more stem cells from the knee capsule to come to the injured area. For those people asking about stem cell numbers that are harvested for treatment, the meniscus is mobilizing the stem cells already in the knee to the site of the its injury.

Research from September 2020: Stem cells live in all the zones of the meniscus

A study published in the journal Arthroscopy (9) wanted to know what type of stem cell populations lived in the meniscus’s red-red (RR), red-white (RW) and white-white (WW) zones and what type of blood flow went into these areas. To find out they performed a study on human cadaver menisci. So, what did they find?

  • There were no significant differences in the clonogenicity (the ability to clone itself to start healing repair) of isolated cells between the three zones.
  • Progenitors (cells like stem cells that differentiate into different types of cells, chondrocytes for example that make cartilage) from all zones were found to be potent to differentiate to mesenchymal lineages.
  • Additionally, results demonstrate the presence of vascularization in the WW zone. The white-white is typically considered unrepairable because it is believed that no blood flow is present.

The meniscus and cartilage are always trying to heal each other

An October 2020 paper titled: “The menisci and articular cartilage: a life-long fascination,” (10) explains that the “menisci and articular cartilage of the knee have a close embryological, anatomical and functional relationship, which explains why often a pathology of one also affects the other.”

In the Journal of orthopaedic research (11) doctors examined the process of meniscal regeneration and cartilage degeneration following meniscus surgical removal in mice. They found that there is a healing environment that the meniscus and cartilage create independently of each other spurred on by native stem cells, that later melds together, suggestive of a balance between meniscal regeneration and cartilage homeostasis. The meniscus and cartilage are trying to regenerate each other.

This special relationship between cartilage, meniscus and stem cells is discussed in research from the University of Iowa. The Iowa findings demonstrate that, much as in articular cartilage, injuries to the meniscus mobilize an intrinsic progenitor (stem cell) population with strong reparative potential.(12) The problem for patients is that despite the desire to heal and regenerate, as pointed out by the Iowa researchers, “Serious meniscus injuries seldom heal and increase the risk for knee osteoarthritis; thus, there is a need to develop new reparative therapies. In that regard, stimulating tissue regeneration by autologous stem/progenitor cells has emerged as a promising new strategy.”

In an animal study of rabbit knees with large meniscal defects researchers found that “(stem cells) injected into the knee adhered around the meniscal defect, and promoted meniscal regeneration in rabbits.” This meniscus regeneration lead to a preservation of the articular cartilage.(13)

PRP and stem cells for meniscus repair

A June 2021 paper (14) discusses the possibility of meniscus regeneration with PRP and stem cell injections. This is a case history.

“Conventional pharmacological and surgical treatments are effective in treating the condition; however, do not result in regeneration of healthy tissues. In this report, we highlight the role of cell-based therapy in the management of medial and lateral meniscal and anterior cruciate ligament tears in a patient who was unwilling to undergo surgical treatment. We injected autologous mesenchymal stem cells obtained from the bone marrow and adipose tissue and platelet-rich plasma into the joint of the patient at the area of injury, as well as intravenously. The results of our study corroborate with those previously reported in the literature regarding the improvement in clinical parameters and regeneration of meniscal tissue and ligament. Thus, based on previous literature and improvements noticed in our patient, cell-based therapy can be considered a safe and effective therapeutic modality in the treatment of meniscal tears and cruciate ligament injury.”

I want to point out that we do not offer intravenous stem cell therapy. This decision is based on more than 20 years of regenerative medicine experience.

PRP injections after meniscus surgery

I am going to return to the study (3) I mentioned above assessing if PRP injections would facilitate healing after a meniscus repair surgery. The authors of this research say:

“Vascularization and nutritional status of the injured meniscus area, as well as the type of meniscus tear, are important indicators for the success of meniscus reconstruction. The inner 2/3 of the meniscus (“white-white”) is nourished by diffusion of factors from the synovial fluid, while the peripheral “red-red zone” has a vascular supply. Between the white-white zone and the red-red zone is a red-white transition zone.

Due to its avascular nature, meniscal healing is a critical issue after injury. In the primary meniscal repair setting, some studies regarding isolated (meniscus) repair in ligament-stable knees observed variable clinical healing or success rates ranging between 33% and 76%. (This means the success was not achieved in 67% and 24% of patients in this range of studies). As many researchers suggest, concomitant ACL reconstruction surgery may improve the healing rates of a repaired meniscus compared to isolated repair. Research has focused on promoting healing with external stimulants, such as fibrin clots, fibrin glue, synovial grafts, periosteum and mesenchymal stem cells. PRP has been widely used in sports medicine with a variety of properties and applied methods.”

In this study, PRP injections were given to people after meniscus surgery and the results were compared to people who had meniscus surgery and no PRP injections. The researchers did not see any real difference. One reason the researchers speculated was PRP was not randomly assigned. The patients who received the PRP was decided on by the surgeon who may have had more extensive damage and who the researchers believed were not good candidates for PRP as “the healing potential in this group was lower.” They also noted on the positive that despite this, “the functional result and failure rate showed a trend that was better than that of the non-PRP group. “

Can stem cell therapy can help your meniscus related knee problems?

A March 2021 study (15) gave this assessment in a paper titled: “Cell-based treatment options facilitate regeneration of cartilage, ligaments and meniscus in demanding conditions of the knee by a whole joint approach.”

“Overall, cell-based regenerative cartilage therapy of the knee has shown tremendous development over the last years and has become the standard of care for large and isolated chondral defects. It has shown success in the treatment of traumatic, osteochondral defects but also for degenerative cartilage lesions in the demanding condition of early osteoarthritis. Future developments and alternative cell sources may help to facilitate cell-based regenerative treatment for all different structures around the knee by a whole joint approach.”

Researchers at the Osaka University Graduate School of Medicine in Japan teamed with the Mayo Clinic to release a January 2020 (16) paper outlining the current research on stem cell therapy for meniscus repair. In this study they wrote:

“Clinical studies evaluating the effects of MSC (stem cell) injections in the knee joint are limited, but early clinical data suggests encouraging results. Currently, there have not been any reported safety concerns or side-effects in the clinical use of MSC injections.

There is only one randomized double-blind controlled study to date studying the effects of MSC injections into the knee post medial meniscectomy (17). The study contained 55 subjects in 3 groups who underwent a percutaneous injection of allogeneic MSCs with one group receiving 50 × 106 cells another 150 × 106 cells and control receiving only hyaluronic acid. At 12 months follow up, MRI scan findings reported a significant increase in meniscal volume in 24% of patients receiving 50 × 106 cells and 6% receiving 150 × 106 cells. None of the control group patients demonstrated an increase in meniscal volume. The study is limited to MRI scan being the only objective outcome measure, but the study methodology is rigorous in that it has the advantage of being blinded and randomized.”

Do you have questions? Ask Dr. Darrow

 

Marc Darrow, MD. JD., discusses the treatment philosophy of the Darrow Stem Cell Institute. Transcript of video

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Platelet Rich Plasma Therapy | Meniscus Tear Injections


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References:

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