A stem cell is a very primitive type of cell that has the capability of multiplying and reproducing itself as well being able to turn into other tissues. Most of the time, we discuss mesenchymal stem cells, which have the ability to turn into bone, cartilage, ligament/tendon, or fat tissue, depending upon their own local environment. In general, stem cells are the cells that help us to repair injured tissue, and the number of stem cells that we have in our body is very small. In addition, as we age, the number of stem cells that we have continues to decline over time. Because the number of stem cells that we have in our own body is very small, they must be carefully separated away from other tissues in our body when they are harvested. After they are separated away, they need to be grown in Petri dishes or other types of culture dishes to try to expand the number of cells present to be able to have a sufficient number of stem cells to be a viable treatment option.
The United States Food and Drug Administration (FDA) carefully regulates the treatment of tissues that are obtained from our body and how they can be treated after they are harvested. The FDA requires that any biologic treatment be minimally manipulated. In general, other than carefully controlled and monitored studies, stem cells are not allowed to be used in our country, and if one wishes to obtain stem cell treatment, this must be done outside the United States, most commonly in countries like Chile, Spain and Germany.
The stem cell injections that most patients believe they are obtaining in the United States are actually not true stem cell injections. In fact, the number of stem cells that are present in the injected material is less than 0.01%. The general hype about the benefits of “stem cell” injections is generally not based on good science.
When one obtains a “stem cell” injection in the United States, most of the time it is bone marrow aspirate from the iliac crest, which has been centrifuged and concentrated. As I mentioned earlier, the true number of stem cells present is very small in this injection. While they may serve as a homing mechanism for other stem cells to enter the area where they are injected, the number of stem cells that are injected has almost no chance to be able to effect a healing process and allow one to have healing of a torn ACL, a meniscus tear, or to restore cartilage surfaces.
This is different than the stem cell injections that are obtained outside the U.S. where pure stem cells may be obtained through growing them in culture dishes and multiplying them into the millions. The literature suggests that there may be a potential, note that this is a potential, for healing of some damaged tissues, and the studies all note that patient’s pain is significantly diminished after these true stem cell injections.
Stem cell injections obtained in the United States from bone marrow aspirate or from adipose (fat) tissue does not significantly improve healing, although it may help to augment healing in a surgery where there is not a good blood supply, such as a meniscus repair.
While the amount of stem cells in a bone marrow or adipose tissue sample, which is centrifuged down or separated and reinjected back into a knee, is very minimal and probably does not have much of an effect on healing, there are some growth factors in other tissues, such as cytokines, which can affect the environment in the knee, which does make a knee feel better. This is especially true for a structure called interleukin-1 receptor antagonist. One of the worse enzymes that can cause a catabolic state in the knee, which makes it sore and angry, is interleukin-1. Interleukin-1 receptor antagonist effectively neutralizes this bad cytokine and can make a knee feel better. It is becoming clear that the centrifugation of bone marrow aspirate significantly increases the amount of interleukin-1 receptor antagonist in some patients. Thus, it is probably this one specific factor which helps to quiet down a knee and makes it feel better, rather than any true benefit from a stem cell effect on healing. In other words, it is probably more a biologic natural neutralizer of the bad enzymes in a knee which makes one feel better from this type of treatment rather than from one having their own cartilage grow back or having a meniscus tear miraculously heal.
The benefits of a bone marrow concentrate injection which has been centrifuged generally takes a few days to up to a week to work. This is because the bad enzymes in the knee can be particularly bothersome and cause a knee’s joint lining to become irritated. Thus, the interleukin-1 receptor antagonist in the bone marrow concentrate injection may help to neutralize the bad enzymes (cytokines) in the knee, which are causing cartilage breakdown, but it may take a few days for the bad effects on the joint lining to quiet down.
Stem cells, in the purist form, can aid in the healing process by helping to heal a tissue back closer to its more normal form rather than forming scar tissue. In addition, stem cells can serve as a homing mechanism through a paracrine effect towards other stem cells which are attached to blood cell walls to migrate to an area of injury. Through this effect, stem cells can help the healing process and better restore tissue such as tendon, muscle, cartilage, bone, or other tissues to heal more effectively when they are injured.
In the United States, where the FDA regulates the processing of one’s biologic tissues to a minimal extent, the cost of processing primarily involves the processing kit, as well as the use of a centrifuge device to try to concentrate down the biologics to a more concentrated form. Thus, the cost of bone marrow aspirates or fat processing systems in the United States can range anywhere from $1,200 to $5,000. In countries where stem cells can be truly purified and multiplied in Petri dishes and processed over a period of weeks to where they are multiplied into the millions, the cost of these stem cell injections can range from $10,000 or more.
In the United States, where our stem cells are allowed to only be processed through minimally manipulated means, there is only a very small chance that a bone marrow aspirate or adipose-derived stem cell technique will assist in the “regrowth” of articular cartilage. While there are studies looking at whether these techniques can augment a microfracture or other cartilage resurfacing technique, these studies have not demonstrated any significant success to date. In European countries and other centers, such as in Chile, where pure stem cells can be grown outside the body and multiplied on Petri dishes, there is some data that show that patients have significant pain relief and that some regrowth of articular cartilage defects may be occurring. It is important to recognize in these studies that they are not pure level 1 studies and they are rather case-control or level 4 studies in the majority of circumstances, so they are not what we would consider definitive studies to demonstrate efficacy of stem cell injection treatment to treat articular cartilage lesions.
In the United States, the use of bone marrow aspirate or adipose-derived stem cell treatment probably helps with pain relief for those patients with pain through the modulation of pain with interleukin-1 receptor antagonist.
In the United States, where biologic products from our own body can only be minimally manipulated, the main purpose of “stem cell injections” for knee arthritis is to alleviate pain. Thus, they are a more biologic form of a corticosteroid or viscosupplementation injection. They should help a knee have less bad cytokines such as interleukin-1 within the knee, so it would help to alleviate pain, but it will not restore articular cartilage in people with bad arthritis and may or may not help people with their knee range of motion. In those patients who have significant swelling, and this is causing decreased motion, a decrease in the swelling may help improve the motion somewhat. However, in patients who have decreased motion because of bone spurs or joint contractures, the chance of a bone marrow aspirate or adipose-derived stem cell injection improving motion are minimal.
The harvesting of biologic products for “stem cell therapy” in the United States primarily involves a bone marrow aspirate from the iliac crest or harvesting fat cells from one’s abdominal area. In both of these circumstances, harvesting can be quite painful in spite of the use of local anesthetics. The pain present can probably be equated to have a dentist work on your teeth when the lidocaine injection has not quite worked as well. It can be uncomfortable for some and quite painful for others.
The injection of the biologic products should be about as painful as any other injection that you would receive within a joint, and it can depend upon whether one hits bone spurs when injecting the product or if one is thin or heavy. Heavier patients have less ability to differentiate along landmarks and may have more pain with these injections.
Does stem cell therapy injections for knees work for patients over 60 years old?
In the United States, where our biologic treatments can only be minimally manipulated per FDA rules, the main goals of “stem cell” therapy are to serve as a biologic alternative to corticosteroid or viscosupplementation injections to try to alleviate pain. Bone marrow aspirate in particular has higher levels of interleukin-1 receptor antagonist, which can bind to and neutralize the bad cytokine interleukin-1, which is known to cause a large amount of the pain associated with osteoarthritis. While the number of stem cells within one’s body declines significantly with ages over 60, it is important to recognize that the number of stem cells present in a bone marrow aspirate is less than 0.01%, and sometimes significantly less than this. So the decreased amount of stem cells that one has in their body with aging may be a moot point in older patients because the main biologic factor which helps with pain relief is the interleukin-1 receptor antagonist. Unfortunately, we do not know whether this particular biologic product changes with aging or not at this point in time.
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