Stem Cell Treatment

Most patients are interested in stem cell treatments because of their potential for tissue regeneration. Although this is an exciting treatment field, it’s an emerging and rapidly developing one, so far mainly driven by idealized outcomes that have not been widely realized in clinical practice.  Stem cells are a group of cells from your own body that have the possibility to become any type of cell in the future depending on the signals they receive. When you are conceived, you are composed of many stem cells that end up forming your organs and different tissues. This group of cells is powerful when you are born, and at that time their healing potential is strong. Throughout life, organs and tissues are constantly changing their cells; dead cells are replaced by new cells derived from your own stem cells. As you grow up, the number of stem cells you have diminishes, stem cells start to lose their potential to regenerate, and aging signs become evident. Besides having a regenerative potential, stem cells are powerful signaling cells: this means they can regulate the body’s inflammatory response, and they can organize which proteins are needed in each case. Because of this ability, stem cells have been proposed as a potential regenerative source for patients with osteoarthritis, which has yet to be proven in vivo.

For treatment purposes, stem cells can be extracted from blood, bone marrow, fat, muscle, and virtually every tissue in the body. Research efforts are currently focused on determining the ideal source for harvesting these cells.

Here it is important to differentiate between two methods of stem cell treatment. One is a single harvesting (known as an aspiration) of the cells, which can be further concentrated via a centrifugation process similar to the one described for PRPand injected. The other, culture-expanded stem cell therapy (aka true stem cell therapy), requires a scientist to isolate the cells, test them for their regenerative capacity, cultured for a couple of weeks so that they multiply, and then reimplanted in the injured area. For the first method, this is a same-day procedure in which the cells are extracted, concentrated, and then injected in the body. The most well-known procedure is a bone marrow concentrate. This procedure is FDA-approved and requires only minimal manipulation of the harvested cells (no chemical addition). The number and type of cells present within the aspiration, however, is generally not optimal; it has been found that in bone marrow aspirates the amount of cells present is 0.001%. Also, these cells may not have the best regenerative potential; the harvesting may yield a mix of stem cells with great, medium, and poor regenerative potential. Bone marrow aspirate has a potential to diminish inflammation even further (when compared to PRP) because of the presence of interleukin-1 receptor antagonist, which is a powerful blocker of inflammation within the joint, which could explain the relative speedy action after the bone marrow injection.

The second type, true stem cell therapy, may have more promise (limited evidence), but it is not FDA approved, and therefore it cannot be performed in the United States if it is not within a clinical trial. It involves harvesting and then isolating the stem cells with the greatest potential to grow and multiplying them by sequential culturing processes that will produce millions of stem cells with the greatest regenerative potential. All of these potential benefits have been proven mostly outside the body (in the laboratory), although the results and their safety profile have not been completely established in humans. That is the reason why they are not yet approved by the FDA as of now.

For both types of therapies, the mode of delivery of stem cells remains a challenge. As of now there are two main ways of implanting stem cells. The first mode is to deliver the stem cells via an injection with a fluid containing the cells. This is done when there is no specific injury, but rather a disseminated injury like osteoarthritis. The second is delivery of the cells through a scaffold that can be implanted (scaffolds are membranes where the cells are implanted so they stay in the  place of the injury). The potential benefits of using a scaffold is that the cells can be placed exactly where they’re wanted. However, these cells may not behave as intended. Recent research has reported that the stem cells that actually induce healing may not be the same stem cells that are injected: they might be coming from different parts of the body. The injected stem cells act as signaling cells, calling other cells in your body to repair the tissues. Also, since stem cells’ actions depend on signaling (they need a signal from the environment they are in to tell them where they are and how to behave), when they are encapsulated in a scaffold, they might not be able to pick up those signals and therefore may not function in the way they’re expected to, creating bone instead of cartilage, for example.

Despite the hype on stem cell use, the information available about stem cell injection outcomes in human patients is limited. The overall reported outcomes are decent, with a relatively safe profile. No major adverse events have been reported. Just a few randomized clinical trials have looked at the effectiveness of bone marrow aspirate (BMAC) for the treatment of osteoarthritis. A recent review identified six trials for osteoarthritis and cartilage defects. It reported that only modest improvement was found and that a placebo effect could not be ruled out with stem cell injections. In another example, researchers from the Mayo Clinic reported on twenty-five patients who had bilateral knee osteoarthritis. BMAC was injected in one knee, and saline (a harmless fluid and salt solution) in the other knee. They reported no difference in symptoms at six months or one-year postinjection between the groups. Reports on outcomes for culture-expanded stem cell therapies are also limited.

Reported side effects for bone marrow aspirate procedure were similar to the ones described for PRP above. The reported frequency of adverse effects after the procedure is 6 to 10 percent of patients. Self-limited pain and swelling are the most commonly reported adverse events. For culture-expanded stem cells, the most concerning adverse effect is that these cells can develop into unwanted tumoral cells. Furthermore, manipulation in the laboratory has risks of contamination of the cells. Researchers from Stanford and Colorado State University stated that unwanted tissues formed after the repair of a cartilage injury in a horse model—bone formed instead of cartilage.

Should I use stem cell injections to prevent getting osteoarthritis?

There is no evidence to support stem cells being used as a preventative treatment for knee arthritis. Current literature on the use of stem cells only provides evidence for diseased joints. Given the fact that no therapy is without risks, it is not recommended that these therapies be used for prevention of joint degenerative disease.

What is stem cell banking?

Adult stem cells are not as powerful as embryonic stem cells because younger cells have higher regenerative potential. Both private and public cord blood banks have been developed in response to the potential for embryonic stem cells (found in umbilical cord blood) to treat diseases of the blood and immune systems. Although there are several stem cell banking facilities, there are no current accepted indications for their use. The sample can later be retrieved only by that individual and for the use by such individual or, in many cases, by their first-degree blood relatives. Health conditions that might benefit from these stem cells include different types of blood diseases, such as myeloma and lymphomas. It is unclear if saving your child’s embryonic cells will be beneficial in the future and therefore is not currently recommended. Private cord blood banking can be costly, ranging from an initial fee of $500 to $2,500, with annual storage fees of $100 to $300 each year thereafter.

A clinical trial on stem cell treatment is offering to enroll me for free. Should I participate?

Because of the relatively safe profile reported in previous studies, enrolling in a clinical trial could be a good option for you if you fit the inclusion criteria for the study. All clinical trials have been screened by an institutional review board that protects patient rights and maximizes patient safety. Carefully read the informed consent form for potential advantages and complications, and make sure you ask all the questions you need answered before enrolling. Of note, you can leave the study at any point without any penalties.

We believe biological therapies will be increasingly used in the future not only in sports medicine and orthopedics but in medicine in general. Further clinical trials with long-term follow-up will help doctors determine how and when to use these therapies and if they are truly safe for patients suffering from arthritis. Several laboratories in the United States are working on biological replacements of joints (trying to regenerate cartilage, instead of using metals) after end-stage osteoarthritis, which could become the gold standard in the future.

The science on these treatments is constantly evolving. Significant changes for the most debated use of stem cells should be expected to occur in five to fifteen years. Their approval and widespread use could be accelerated, should researchers find the right therapy and timing for its use. Exciting times are coming in the field of orthopedics because these therapies can dramatically change the way we practice medicine.