Stem Cells

Stem cells are a specialized subset of cells within the body that are capable of dividing for the purpose of replenishing themselves and differentiating into specialized cells of the body, which are able to complete certain tasks (Bellehsen, Nagler, & Levi-Schaffer, 2008). For example, a stem cell might divide to create new stem cells, or to create a cell capable of undergoing biological transformation into a heart, lung, skin or other type of cell needed within the body.

For decades, researchers have investigated the means by which stem cells could be harnessed in medicine. Perhaps the most notable application of stem cells in medicine are the use of bone marrow and blood stem cell transplants to restore stem cells lost to chemotherapy in the treatment of cancers (ExitCare, LLC, 2011). Investigators are finding other potential uses for stem cells as well. The following are some of the conditions for which stem cells are being investigated as a potential medical treatment:

  • Spinal Cord Injury (SCI)
    • Animal studies have shown promise for stem cell therapy in preventing and treating pain associated with spinal cord injury (Hendricks, et al., 2006).
  • Multiple Sclerosis
    • Stem cell transplantation has also shown promise in the treatment of patients with multiple sclerosis, an autoimmune inflammatory disease in which the conductive coating of neurons degenerates in the central nervous system causing disability (Olek, 2012)
  • Inter-vertebral disc degeneration
    • The spine consists of a column of bones, known as vertebrae, which are stacked atop one another from the pelvis to the base of the skull, protecting the spinal cord. Each of these vertebrae are separated by cartilaginous, inter-vertebral discs composed of a tough, fibrous outer layer and filled with a soft, gelatinous inner layer. These discs support the vertebrae and allow them to shift across one another, facilitating movement of the spine. When these discs degenerate, they can cause nerve compression and chronic low back pain (Drazin, et al., 2012). Inter-vertebral disc degeneration, one of the major causes of low back pain, has shown particular promise as a target for stem cell therapy. In 2003, animal studies showed that stem cells slowed the rate of disc degeneration and preserved disc structure (Sakai, et al., 2003). Two years later, these researchers were able to show that transplanted stem cells differentiated into cells resembling the inter-vertebral disc (Sakai, et al., 2005). In one case report, researchers were able to shown regeneration of meniscus cartilage in a patient experience debilitating pain from osteoarthritis (Centeno, et al., 2008). Trials in humans are expected in the near future.

Stem cells are being investigated for many other medical applications as well, including ACL reconstruction, muscular dystrophies and more (Bagaria, et al., 2006). Stem cells are also currently used in cosmetic medical procedures. Even more exciting, however, are the stem cell therapies currently available for the treatment of conditions causing chronic pain. Many stem cell therapies have shown benefits and good outcomes during clinical studies, most of which are for the treatment of soft tissue and bony injuries. Research has shown that stem cells can aid in the recovery and replenishment of tendon, bone, cartilage and muscle tissue (Centeno, et al., 2008). Examples of painful conditions currently treated with stem cells by pain management specialists include osteoarthritis and other cartilage and tendon injuries.

Anatomy and Physiology

There are two basic types of stem cells, embryonic and adult (Bellehsen, Nagler, & Levi-Schaffer, 2008):

  • Embryonic stem cells are isolated from a structure in a four- to five-day-old embryo, termed a blastocyst. Embryonic stem cells are capable of differentiation into nearly any type of cell in the body, ranging from neurons to heart cells, a condition termed pluripotency. Embryonic stem cells are harvested from embryos, usually surplus embryos from reproductive in-vitro fertilization procedures.
  • Adult stem cells are isolated from specific tissues within the body of consenting, adult individuals. These cells are most commonly harvested from bone marrow, teeth, adipose tissue (fat cells) and blood. Adult stem cells tend to be unipotent or multi-potent, in that they can divide, but only differentiate into one, or a few, related types of specialized cells. An example would be a stem cell giving rise to both keratinocytes and melanocytes, each of which is a skin cell found in the skin. Rarely, these stem cells can be pluripotent in cases of umbilical cord blood harvesting. In recent years, researchers have discovered ways to induce pluripotency in some adult stem cells to circumvent the ethical and moral issues associated with embryonic stem cell collection and use.

One class of adult stem cells in particular, mesenchymal stem cells (MSC’s), are important in emerging treatments for chronic pain. Unlike most adult stem cells, MSC’s are pluripotent, thus gaining the advantages of embryonic stem cells without the ethical questionability surrounding embryonic stem cell harvesting. MSC’s can be easily collected and grafted to injured tissue, thus serving as a primary source of stem cells in therapeutic applications for chronic pain (Drazin, et al., 2012).

A third type of stem cell currently gaining traction for the treatment of pain due to wounds and soft tissue and bony injuries are amniotic stem cells, which are largely comprised of MSC’s (Steed, et al., 2008). These cells are harvested from the amniotic fluid that cushions and nourishes a fetus while to develops within the womb during pregnancy. These stem cells can also differentiate into a variety of different cell lines such as bone, nerve, muscle and skin.

Procedure

Prior to a stem cell therapy procedure, the cells themselves must be acquired. Stem cells can originate from the patient themselves (autologous) or a close donor match (homologous or allogenic) (ExitCare, LLC, 2011). For procedures involving autologous transplant, the stem cells are first harvested from a patient, and then spun down in a centrifuge to allow gravity to separate the stem cells by weight. These stem cells can be collected via needle from blood, bone marrow or adipose tissue depending upon the procedure to be performed. For allogenic transplants, this same harvesting procedure is done with a donor, and the stem cells are stored for later use. For treatments involving amniotic stem cells, the cells are harvested from amniotic fluid during cesarean section and frozen for later use (Applied Biologics, 2011). Also, depending upon the procedure, before injection the stem cells collected may be supplemented with platelet-rich plasma (PRP). PRP consists of blood plasma concentrated to include higher than normal numbers of platelets, a cell that provides a multitude of protein growth factors involved in many other biological responses involved in healing and tissue repair (Mishra & Pavelko, 2006).

The source of stem cells may differ depending upon the type of procedure being performed. For most orthopedic applications, and procedures for the treatment of chronic musculoskeletal pain, bone marrow or peripheral blood serves as the best source of stem cells (Regenexx, 2010). For cosmetic applications of stem cells or procedures using stem cells for the treatment of nerve degeneration, adipose or fat tissue is often the best source.

The procedure for stem cell treatments differ depending upon the nature of the treatment and goals for therapy. However, all stem cell therapy procedures follow a basic outline. A patient is informed of all benefits, risks and alternatives to a stem cell therapy, before the procedure is scheduled. If harvesting of the stem cells is required, it is usually done in the morning before the procedure, such that the stem cells can be prepared before the patient returns in the afternoon. Harvesting involves using a needle to draw stem cells from the blood, adipose tissue or bone marrow by direct puncture of a flat bone, such as the hip.

Once the stem cells are prepared and available, a patient is comfortably positioned on a procedural table such that an injection or operative site is accessible to the physician (Centeno, et al., 2008). The site is then cleaned and sterilized, and the patient may be given local or general anesthesia to prevent any discomfort associated with the procedure. Once preparations are complete, a needle is guided to the target site of degenerated tissue, and the stem cell solution is injected directly to the area (Centeno, et al., 2008). The needle is often guided with radiographic assistance, such as ultrasound or fluoroscopy, a type of real-time x-ray.

For outpatient procedures, such as stem cell therapy for low back pain or soft tissue injuries, patients are often able to return home following a short period in which medical staff can monitor a patient for any adverse reactions. Any extra stem cells collected for the procedure can be cryo-stored (frozen) for future use.

Benefits

Based on very early, but very promising case studies in which stem cells are used for the treatment of osteoarthritis and cartilage and tendon injuries, patients receiving stem cell therapy for chronically painful conditions can expect to see improvement in pain and in quality of life following the procedure. A major benefit of utilizing stem cell therapy for the treatment of chronic pain is that if successful, it can delay or even replace the need for surgical intervention.

Risks

As with any medical procedure involving injection or access through the protective skin barrier, infection and bleeding are a risk. These risks are minimal however, and stem cell therapy for the treatment of chronic pain associated with muscle, bone, tendon and cartilage disorders is considered very safe.

Patients should monitor their injection/operative site closely following the procedure, observing for any increased pain, redness, swelling or discharge which may require immediate medical attention. Patients can follow up with their pain management physician for any concerns.

Given the nature of stem cell’s ability to differentiate, and the infancy of stem cells for medical therapy, there has been significant concern in the medical community as to whether or not stem cell therapies might become cancerous. Thus far however, studies performed to assess this possibility have reported no cancerous complications associated with stem cell therapy (Centeno, et al., 2011).

Outcomes

In one pilot study designed to evaluate the effectiveness of implanting stem cells to treat degeneration of bone, researchers found that when compared to controls, patients receiving autologous stem cell therapy reported greater improvement in pain and other symptoms and were less likely to progress to further bone degeneration (Greenspan & Gershwin, 2008). Follow up studies have shown that stem cells can halt progression of bone degenerative disease. Many case reports report similar findings for conditions ranging from tendon injuries to osteoarthritis.

Stem cell therapies are certainly in their infancy; However, early studies show great promise for the use of stem cells in the treatment of a variety of musculoskeletal conditions causing chronic pain. With time and research over the next few years, many more applications of stem cell therapy will undoubtedly arise. Patients experiencing chronic pain should consult with a pain management specialist to find out of stem cell therapy may be appropriate for pain management, or as an alternative to surgery.

References
Applied Biologics. (2011). Amniomatrix FAQ. Retrieved from Applied Biologics Website: http://www.appliedbiologics.com/index.php/frequently-asked-questions

Bagaria, V., & al., e. (2006). Stem cells in orthopedics: Current concepts and possible future applications. Ind J Med Sci , 162-169.

Bellehsen, L., Nagler, A., & Levi-Schaffer, F. (2008). Stem Cells: What Are They and Why Do We Need Them? Retrieved from MD Consult. Adkinson: Middleton’s Allergy: Principles and Practice, 7th ed.

Centeno, C., & al., e. (2008). Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physician , (11) 343-353.

Centeno, C., & al., e. (2008). Regeneration of meniscus cartilage in a knee treated with percutaneously implanted autologous mesenchymal stem cells. Med Hypo , (71) 900-908.

Centeno, C., & al., e. (2011). Safety and complications reporting update on the re-implantation of culture-expanded mesenchymal stem cells using autologous platelet lysate technique. Curr Stem Cell Res Ther , (6) 368-78.

Drazin, D., & al., e. (2012). Stem Cell Therapy for Degenerative Disc Disease. Advances in Orthopedics , 1-8.

ExitCare, LLC. (2011). Bone Marrow Transplantation & Peripheral Blood Stem Cell Transplantation: Q & A. Retrieved from MD Consult. Patient Education.

Greenspan, A., & Gershwin, M. (2008). Osteonecrosis. Retrieved from MD Consult. Firestein: Kelley’s Textbook of Rheumatology, 8th ed.

Gurtner, G., & al., e. (2007). Progress and Potential for Regenrative Medicine. Annu Rev Med , 299-312.

Hendricks, W., & al., e. (2006). Predifferentiated Embryonic Stem Cells Prevent Chronic Pain Behaviors and Restore Sensory Function Following Spinal Cord Injury in Mice. Mol Med , (12) 1-3.

Mishra, A., & Pavelko, T. (2006). Treatment of Chronic Elbow Tendinosis with Buffered Platelet-Rich Plasma. Am J Sports Med , 1774-1778.

Olek, M. (2012). Treatment of progressive multiple sclerosis in adults. Retrieved from In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA.

Regenexx. (2010). Having Many Stem Cell Sources in the Toolbox benefits the Patient. Retrieved from Regenexx: http://www.regenexx.com/2010/12/having-many-stem-cell-sources-in-the-toolbox-benefits-the-patient/

Sakai, D., & al., e. (2005). Differentiation of Mesenchymal Stem Cells Transplanted to a Rabbit Degenerative Disc Model: Potential and Limitations for Stem Cell Therapy in Disc Regeneration. Spine , (30) 2379-2387.

Sakai, D., & al., e. (2003). Transplantation of mesenchymal stem cells embedded in Atelocollagens gel to the intervertebral disc:a potential therapeutic model for disc degeneration. Biomaterials , (24) 3531-3541.

Steed, D., & al., e. (2008). Amnion-derived Cellular Cytokine Solution. Eplasty .