Stem Cell Basics
Stem cells are basic cells that can give rise to almost any type of specialized cell in the human body. If a stem cell is in an area where there are damaged tendons, they will give rise to cells that can make new tendons. In Musculoskeletal Medicine (MSK Medicine), we are most interested in mesenchymal stem cells that make and repair the supporting tissues of the body: tendons, ligaments, cartilage, and the spinal discs. Up to now, mesenchymal stem cells were mostly obtained from bone marrow, but fat has 500 times the mesenchymal stem cells found in bone marrow, so it is now the preferred source. The use of stem cells and similar tissue is called Regenerative Medicine.
Regenerative Medicine is the use of substances from the patient’s own body to restore or establish function. This allows the treatment of damaged tissues and organs by stimulating the body’s own repair mechanisms to heal tissues or organs previously not repairable. Simply put, Regenerative Medicine is the use of your own body to heal itself.
The newest advances in regenerative medicine was first the use of platelet rich plasma (PRP), and now the use of adult mesenchymal stem cells. Both are taken form the patient’s own body and used the same day, so there is no chance of rejection or getting an infection from a donor. Since they are taken from the patient, they are adult stem cells and not embryonic stem cells, so there is none of the controversy that is associated with embryonic cells. To be legal in the United States, stem cells cannot be cultured to increase their numbers. That is why using adipose tissue derived stem cells works better than stem cells from bone marrow, which have to be cultured to work best.
Platelet Rich Plasma (PRP) is made by drawing blood from the patient and then the whole blood is centrifuged to concentrate the platelets. Platelets are responsible for the initiation of clotting, but also the initiation of healing. To get stem cells from fat (adipose tissue), a small amount of fat is obtained by syringe liposuction and then the stem cells are harvested from the fat. The stem cells are then suspended in PRP, so you get both at the same treatment. The stem cells are then administered by injection.
All tissues break down and are repaired by restorative cells. How do stem cells work? We can look at degenerative disc disease (DDD) as an example. The disc is made up of a wall and a gel-like center. In the center are the cells that repair the disc wall as it breaks down. In DDD, the wall breaks down faster than the disc cells can repair it, and the number of disc cells diminishes with time. By adding stem cells which turn into disc cells, the wall can be repaired and if done early enough, the disc may become nearly normal.
More on Regenerative Medicine and Musculoskeletal Medicine (MSK Medicine) in future installments.
Stem Cells in Neck and Low Back Pain
In my last article, I talked a little about the use of regenerative medicine in the treatment of low back pain. Today, we will go into spine pain in more detail. This pertains to pain in the low back, mid back and the neck.
The spinal disc is responsible for most low back pain and we will concentrate on it here. The disc is made up of a strong outer wall, the annulus, and a gel-like center, the nucleus. It is located between the vertebral bodies. The outer annulus allows strength and motion. The inner gel contains the cells that repair the disc wall as it breaks down and strong chemicals that are very irritating if they get outside the disc. Degenerative disc disease is caused in most, if not all cases, by a genetic abnormality where the amino acid building block sequence is abnormal. This causes the disc wall to break down faster than the disc cells can repair it, leading to cracks, fissures and tears. The central gel material can protrude into and through these cracks and tears. The chemicals in the gel can irritate the ligaments and nerves causing buttock and leg pain. The tear itself can be a source of pain. There can also be mechanical pressure on the nerves, causing leg pain.
The Treatment Of Spinal Disc Pain
Placing steroid medication in the space around the disc (the epidural space) can calm down the chemical irritation that is due to the chemicals that have leaked outside the disc. If there is no chemical leakage, the epidural is not very helpful. Typically, the epidural steroid injections work well at first, then become less effective.
To Treat The Tears Inside The Disc, Medications Have To Be Placed Inside The Disc.
More recently platelet rich plasma (PRP) is being injected into the disc. Platelets are in blood and they stop bleeding, but also initiate healing. The exact mechanism of action is not understood, but PRP injected into the disc usually works better and lasts longer than chondroitin and glucosamine injections. The most powerful treatment for degenerative disc disease is the injection of stem cells into the disc. In degenerative disc disease, the naturally occurring disc cells die off. The stem cells injected replace the cells that have died off. (See the article in the June issue for more on how stem cells work.)
In PRP injections, blood is taken from the patient and the platelets are concentrated before they are injected back into the patient on the same day. Stem cells can be harvested from either bone marrow or adipose tissue (fat); however adipose tissue has 500 times the stem cells as bone marrow. As with PRP, stem cells must be harvested, concentrated but not cultured, and injected back into the same patient on the same day.
More on the treatment of other causes of spine pain in future articles.
– R K Silbert, M.D.
The Use of Mesenchymal Stem Cells and Platelet Rich Plasma in the Treatment of Sports Injuries
Many famous athletes have used either platelet rich plasma (PRP), mesenchymal stem cells or both, to treat injuries such as knee sprains and chronic tendon injuries. Examples include Tiger Woods, Payton Manning, Jeff Saturday, Rafael Nadal, Hines Ward, and many others. These types of conditions have typically been treated with medications, physical therapy, or even surgery. PRP and more recently mesenchymal stem cells have allowed these athletes to be able to return more quickly to competition. Pittsburgh Steelers’ Hines Ward and Troy Polamalu used it before winning Super Bowl XL. Presently, PRP use in tendon and ligament injuries has several potential advantages, including faster recovery and, possibly, a reduction in recurrence, with no adverse reactions described.
Sports injuries include injuries to the tendons, ligaments, joints and muscles. Rotator cuff injuries of the shoulder and tendon injuries of the elbow are very common, but any tendon or ligament can be involved. Sprains are ligament injuries, and involvement of the knee and ankle are common, as are hamstring injuries in runners. All of these injuries usually require the athlete to be out of action for a prolonged time.
In older, and sometimes not so old athletes, joint problems due to osteoarthritis can limit participation. Steroid injections can help temporarily, but are detrimental in the long run, so are limited to a few a year. PRP injections improved pain and function, and in up to 73% of patients, appeared to delay the progression of osteoarthritis, which is a progressive disease. Individuals treated with mesenchymal stem cells to the knee have had a 75% decrease in pain scores and a 75% improvement of lifestyle scores at six months after treatment. The injection of mesenchymal stem cells is the only treatment short of joint replacement for avascular necrosis, which is bone death. Mesenchymal stem cells injection is the only treatment, medical or surgical, that has shown enough increase in growth of both articular and meniscal cartilage of the knee for the increase to be seen on MRI.
Pain from the discs of the neck and back can also limit athletic performance and can be treated by stem cell therapy. There are ongoing studies that are very promising.
As explained in previous issues, platelets initiate healing and are found in the blood. PRP is made by spinning the blood to concentrate the platelets and then injecting the concentrated platelets into the injured tissue. Stem Cells can be derived from either the body fat or the bone marrow. Fat or adipose tissue has five hundred times the number of the type of stem cells needed to repair sports injuries, so it is preferred. The FDA will allow the use of stem cells for treatment if they are used in the same day in the same patient from which the are taken. Embryonic stem cells are not legal and are not used for sports injuries in the United States.
Effects of the Intradiscal Implantation of Stromal Vascular Fraction Plus Platelet Rich Plasma in Patients With Degenerative Disc Disease
Stromal vascular fraction (SVF) can easily be obtained from a mini-lipoaspirate procedure of fat tissue and platelet rich plasma (PRP) can be obtained from peripheral blood. The SVF contains a mixture of cells including ADSCs and growth factors and has been depleted of the adipocyte (fat cell) population. We evaluated the safety and efficacy of administering SVF and PRP intra-discally into patients with degenerative disc disease.
A total of 15 patients underwent a local tumescent liposuction procedure to remove approximately 60 ml of fat tissue. The fat was separated to isolate the SVF and the cells were delivered into the disc nucleus of patients with degenerative disc disease. The subjects were then monitored for adverse events, range of motion, visual analog scale (VAS), present pain intensity (PPI), Oswestry Disability Index (ODI), Beck Depression Inventory (BDI), Dallas Pain Questionnaire and Short Form (SF)-12 scores over a period of 6 months. Safety events were followed for 12 months.
No severe adverse events (SAEs) were reported during a 12 month follow up period with no incidences of infection. Patients demonstrated statistically significant improvements in several parameters including flexion, pain ratings, VAS, PPI, and short form questionnaires. In addition, both ODI and BDI data was trending positive and a majority of patients reported improvements in their Dallas Pain Questionnaire scores.
Overall, patients were pleased with the treatment results. More importantly, the procedure demonstrated a strong safety profile with no severe adverse events or complications linked to the therapy.