What do we know about using stem cells?

What is the potential for Stem Cells?

Almost everyone would agree that we are just starting to understand the potential for using stem cells. Over the next few years to decades, we are looking at a probable explosion of uses in many areas of medicine. Disorders that currently require chronic management are likely to be cured, and no longer require ongoing medical care. Other disorders with poor or marginal alternatives for management will see the quality of the care improve dramatically. Sports medicine may well see a revolution in management of injuries, with shortened recoveries and improved results. But these things are in the future. What do we know about using stem cells NOW? The following is a brief overview.

Where do Stem Cells come from?

Any discussion of the use of stem cells has to address the origin of the cells themselves. The first identified stem cells were embryonic. This means they come from cells early in the development of an infant. Another origin of stem cells is newborn infant cord blood. Stem cells obtained from adults include hematopoietic (blood or bone marrow) and adipose (fat tissue) derived. Most tissues in the body have some stem cells, but these are the tissues that provide a large enough number of available stem cells for medical use. If stem cells that are used come from another person, they are called allogeneic. If stem cells that are used come from the person using them, they are called autologous. In the United States, embryonic stem cells are considered controversial and face significant restrictions in their use. We will not discuss them further here. Some clinicians and companies are storing cord blood in newborn for potential future use. This has not yet become widespread and the cells currently have rare usage. We will not further discuss them here. The rest of the discussion will center on the use of adult stem cells.

How are Stem Cells used right now in the United States?

In the United States, bone marrow transfer has become the preferred treatment for many blood disorders such as leukemia and myelodysplasia. The cells that result in a life-saving response are hematopoietic stem cells. These are typically allogeneic, but increasing are becoming autologous. The vast majority of US studies have been done using hematopoietic cells. Outside of blood disorders, stem cells are viewed almost solely as in investigational treatment. The United States Food and Drug Administration (FDA) has not approved stem cells for the treatment of any disorder. Put simply, the only area of widely accepted use of stem cells in the US is in certain blood disorders.

Is there a difference in Stem Cells?

The short answer to this question is probably not – stems cells have the same potential no matter where they come are harvested. Unfortunately, there is some controversy over whether hematopoietic or adipose derived stem cells work better for certain uses. Sometimes this controversy can become quite heated. More recent studies (1,2) have shown that hematopoietic and adipose cells share the same characteristics. Studies have also shown that adipose derived stem cells do not decrease very much in number with age. Hematopoietic stem cells do decrease in number and availability with age. Since adipose derived cells are more abundant, easily acquired and remain available with age, we will discuss their use for the rest of this article.

What is an autologous adipose derived Stem Cell?

These are some unfamiliar words used to describe some familiar concepts. Autologous means simply – you. Cells or tissues that come from your own body are autologous when given back to you. Adipose is also something we are all familiar with – fat. Adipose derived means simply coming from fat. So, autologous adipose derived stem cells means stem cells coming from your fat. It’s that simple. We are giving you back to you. In the literal sense as in your cells, and figuratively when the deployment has good results. However, since we never like anything simple in medicine, the final product we have when we process autologous adipose derived fat cells (your stem cells from your fat) is not just stem cells. It is a mixture of stem cells and special body chemicals called growth factors. This final product is known as the stromal vascular fraction (SVF)

What is the Stromal Vascular Fraction?

Stromal vascular fraction (SVF) is the name given to the final product present when fat is harvested to obtain stem cells. SVF contains stem cells, other tissue cells like pre-endothelial (blood vessel) cells, macrophages (white blood cells) and growth factors. Of these, it appears the stem cells and growth factors play the most important roles. Growth factors are one of the primary methods that our cells talk to each other. Growth factors are very powerful. They can tell stem cells to turn on and start making new cells in a tissue. They can make an area inflamed or decrease inflammation in an area. They cause many types of cells to move, multiply and activate all in the cause of promoting healing. The combination of growth factors and stem cells in SVF give it an amazing potential for healing and regeneration. Our primary purpose is the study the safety and efficacy of deploying SVF in a high quality and consistent manner for a number of clinical disorders.

How is SVF deployed?

We refer to using the Stromal Vascular Fraction (SVF) as deployment. SVF can be deployed in several ways. The most commonly used deployment methods are:

  1. Into a specific joint such as a knee for arthritis in that joint. Most patients with osteoarthritis and other joint disorders are familiar with steroid injections in the joint. This process is similar.
  2. Into a specific joint under image guidance. This involves using x-ray, ultrasound, MRI or other imaging tools to insure the SVF is deployed directly into the joint. This is most commonly used in deep joints like the back, neck or shoulder.
  3. Directly into an area of soft tissue. This is common with disorders such as neuropathy or non-healing ulcers. It can also be done with imaging for muscle or ligament/tendon injuries.
  4. Intravenous (IV) deployment is common. This is used in many neurologic and auto-immune disorders along with others.
  5. More than one of these may combined in the same patient for diseases like rheumatoid arthritis or multiple disorders.

As we learn more, additional deployment methods may be added.

For what disorders are stem cells (SVF) used that reap benefits of stem cell therapy?

As stated above, stem cells are used for certain blood disorders in the United States. All other use of stem cells or SVF in the United States is considered investigational. Many disorders have investigational protocols. We can group them like this:

  1. Orthopedic problems such as osteoarthritis, post traumatic arthritis and soft tissue injuries.
  2. Auto-immune or connective tissue disorders such as rheumatoid arthritis and scleroderma.
  3. Neurologic disorders such as multiple sclerosis, Parkinson’s disease or stroke.
  4. Lung problems such as chronic obstructive pulmonary disease (COPD).
  5. Gastrointestinal disease such as Crohn’s disease or auto-immune hepatitis.
  6. Cardiac disease such as congestive heart failure (CHF).
  7. Urinary disease such as interstitial cystitis or erectile dysfunction.
  8. Eye disease such as macular degeneration, retinitis pigmentosa and diabetic retinopathy.
  9. Dermatologic conditions such as hair loss and lichen sclerosis.

In the near future, new investigational protocols will be added to this list. We will next talk about each of these deployments.

How are stem cells (SVF) used in arthritis?

Orthopedic uses will probably see the most rapid advance of any area over the next few years. A number of high profile individuals such as governors and professional athletes have had effective stem cell deployment in the last year or two. The knee has probably been the most frequently done. Unpublished results show patients who have been recommended to have knee have an 85% reduction in pain and a similar improvement in function. So far, less than 5% have gone on to have knee replacement. It is important to remember that these are early results and will probably change over time, but they are encouraging. Other joints have included:

  1. Hip
  2. Shoulder
  3. Elbow
  4. Ankle
  5. Wrist
  6. Fingers
  7. Back and spine
  8. Neck

Although encouraging, results are still too early to discuss on these joints. Some of these joints like the knee, hip and elbow can be done in the physician’s office using ultrasound or no visualization. Other joints such as the back and neck, are best done at an imaging center using CT or other techniques to assure the SVF is placed within the joint.

Soft tissue injuries are also seeing rapid expansion of stem cell (SVF) use. Soft tissue refers to things like muscles, ligaments and tendons that do not involve the bone or joint. Soft tissue deployments are being used in:

  1. Tendon injuries such as the Achilles tendon.
  2. Muscle injuries or tears such as a torn or sprained hamstring.
  3. Chronic tendonitis.
  4. Overuse injuries.

Soft tissue use also is too early along to report. Veterinary work is much more advance in the US due to fewer restrictions in use. The results of use in animals, especially horses, are very encouraging.

How are stem cells (SVF) used in auto-immune (connective tissue) disorders?

Auto-immune or connective tissue disorders are an exciting area for the use of stem cells or SVF. Many of these disorders have only a moderate or poor response to traditional treatments.
Deployment protocols are available for:

  1. Rheumatoid arthritis.
  2. Scleroderma.
  3. Systemic Lupus Erythematosis.
  4. Relapsing polychrondritis
  5. Alopecia areata.
  6. Myasthenia Gravis.
  7. Fibromyalgia.

Some might classify the last two disorders elsewhere, but we have classified them here for deployment protocols. Results of treatment of these disorders have also been encouraging. Early results suggest that repeat treatments may be required every 6-12 weeks. It has been postulated that this may be due to the anti-inflammatory effects of the growth factors present in SVF. This area has several types of deployment use. All of them use IV deployment. However, inflamed localized joints can receive joint injections. Localized soft tissue injections can also be done in areas of involved skin, muscular trigger points or scalp.

How are stem cells (SVF) used in neurologic diseases?

Perhaps the area that has generated the most interest in stem cells (SVF) is their use in neurologic disease. The ability to treat spinal cord injuries, Parkinson’s disease or multiple sclerosis is truly exciting. The neurologic diseases with a SVF deployment protocol available are:

  1. Parkinson’s disease.
  2. Multiple Sclerosis.
  3. Stoke.
  4. Muscular dystrophy.
  5. Neuropathy
  6. Spinal cord injuries.

Most of these disorders receive IV deployment. In addition, neuropathy and spinal cord injuries receive soft tissue injections into the area of concern/injury. In the case of spinal cord injury, this is usually done under CT imaging. Early results are encouraging but no numbers are available. Many studies are underway to determine the most effective method to treat these disorders using stem cells. We will continue to see advances in the neurologic use of stem cells for years to come. Some patients require repeat treatments in 6-12 weeks depending upon response.

Bibliography

1. Cell Tissue Res. 2012 Nov;350(2):277-87. doi: 10.1007/s00441-012-1453-1. Epub 2012 Jun 5.
The comparition of biological characteristics and multilineage differentiation of bone marrow and adipose derived Mesenchymal stem cells. Zhu X, Shi W, Tai W, Liu F.

2. Clin Lab. 2012;58(9-10):897-903.
The comparison of multilineage differentiation of bone marrow and adipose-derived mesenchymal stem cells. Zhu X, Du J, Liu G.