Stem Cell Prolotherapy: The New Frontier of Pain Management

Stem Cell Prolotherapy is the most exciting addition to the regenerative medicine field of Prolotherapy.  A person’s own healing cells are obtained from bone marrow, fat, and blood (in various combinations or alone) and then injected into the area which has a cellular deficiency. The goal is to stimulate the repair of injured tissues just like dextrose prolotherapy and PRP.

Dextrose Prolotherapy and Platelet Rich Plasma (PRP) Prolotherapy are designed to stimulate the repair of injured tissues. However, they are both dependent on the body having a sufficient amount of repair cells available at the site of the injury.  "Cellular depletion" occurs if a joint area has been chronically injured and inflamed over an extended period of time.  There are fewer repair cells available as they have been used up over time.   If cellular depletion has occurred, local repair stem cells will not be available and/or the available ones will be used up quicker after a few treatments of dextrose prolotherapy and/or PRP. Stem Cell Prolotherapy as it can be more effective than dextrose prolotherapy or PRP when cellular depletion occurs. It involves taking good repair cells from either the bone marrow or the adipose (fat) tissue, both known to contain adult stem cells, and injecting them into the injury site. Despite this difference in effectiveness when cellular depletion occurs , the common goal of Dextrose Prolotherapy, Platelet Rich Plasma Prolotherapy and Stem Cell Prolotherapy is the stimulation of the injured tissues to repair and regain their strength.

A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework stroma for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells of connective tissue in animals.Chondrocytes are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans.

Stem Cell Prolotherapy assists in fibroblastic proliferation as well as chondrocyte proliferation. In stem cell prolotherapy, the tissues which are being targeted to stimulate to repair can include articular cartilage in addition to soft tissues structures such as ligaments and tendons. Needle placement of the stem cells will determine which tissues are being targeted.

Autologous stem cells are the stem cells that your bodies produce. Autologous stem cells are not embryonic stem cells. They are adult “Mesenchymal Stem Cells” (MSC’s). Stem cells may exist in every tissue, with bone marrow and adipose tissue serving as the body’s main sources from which extra repair stem/stromal cells are mobilized when needed.   For close to twenty years, researchers have been studying the use of adult "Mesenchymal Stem Cells" (MSC's) in tendon repair. They have discovered that the use of implanted adult stem cells delivered to tendon defects improves the biomechanics, structure, and function of the injured tendon.  MSC's were deemed to be safe for human use in 1995 which led to increased research efforts.  The use of minimally manipulated autologous stem cells for orthopedic conditions is FDA-cleared, therefore it is neither controversial nor dangerous. The use of MSC’s is legal and safe.

MSC’s can be harvested and injected into our own degenerated joints and ligaments. As stated above, these cells upon contact with damage joint surfaces or other damaged tissue are able to determine which cells are damaged and which are not. These repair cells target and repair areas of tissue injury, including osteoarthritis and other injured types of tissue such as ligaments and tendons.  In certain degenerative diseases such as osteoarthritis, an individual's stem cell potency appears depleted, with reduced proliferative capacity and ability to differentiate. MSC’s target these cells resulting in the creation of new cell tissue.

Stem Cell Prolotherapy is the next frontier for prolotherapy aimed at creating joint regeneration and/or spine regeneration. It is a minor medical and surgical procedure in which stem cells are taken from bone marrow aspiration and/or adipose tissue (fat cells). The procedure is very innovative but it only takes about an hour with conscious sedation.

CONDITIONS CONSIDERED FOR TREATMENT WITH STEM CELL PROLOTHERAPY INCLUDE:

1. Lower Back Pain

2. Joint Osteoarthritis

3. Shoulder Pain

4. Joint Pain

5. Hip Pain

6. Knee pain

Bone Marrow Derived Stems

Our bone marrow contains stem cells, also termed adult “mesenchymal stem cells” and progenitor cells, among other names. These immature cells have the ability to become tissues like cartilage, bone, and ligaments.

Concentration of the bone marrow is an important element of efficacy and there are FDA approved devices which concentrate the bone marrow into what is called “Bone Marrow Aspirate Concentrate” (BMAC).   This autologous bone marrow aspirate contains not only adult “mesenchymal stem cells” (MSC’s) but also accessory cells that support angiogenesis and vasculogenesis through the production of growth factors and cytokines.

Bone marrow is harvested from the hip using local anesthetic and a specialized needle. Bone marrow harvesting for Bone Marrow Aspirate Concentrate (BMAC) is  different from bone marrow harvesting for transfusion for cancer therapies. In bone marrow harvesting for transfusion, a hematologist, oncologist, or surgeon removes a very large amount of bone marrow. BMAC requires only a very small amount of bone marrow. The BMAC procedure is not painful and causes only mild soreness after completion. This procedure takes 10 mintes or less and has an outstanding safety profile with very low morbidity.

Degenerative osteoarthritis is typically progressive, degenerative, and the joint has a limited ability to heal itself. The joint physiology is in a catabolic state thus breaking down. The goal with BMAC is to make the joint physiology convert to an anabolic state so that it is in a building mode as opposed to breaking down. Stem Cell Prolotherapy, using bone marrow, is stimulating the body to repair the area and strengthen it. The cells in the extracellular matrix that articular cartilage is composed of are called chondrocytes. BMAC’s proposed mechanisms include the following:

• Reduces the joint instability that originally led to the degenerative arthritis.

• Stimulates the growth of new cells that create the extracellular matrix which is causing the chronic pain and/or instability.

• Stimulates the cells already present to make extracellular matrix.

• Injected precursor cells (stem cells) will differentiate into adult articular cartilage cells (chondrocytes).

Adipose Derived Stem/Stromal Cells

Human adipose tissue (fat) is a rich source of adult stem cells. It possesses a population of cells with extensive proliferative capacity, and the capability of differentiating into multiple cell lineages. It is common for many individuals to electively undergo liposuction procedures, which yield large volumes of useable adipose tissue. For this reason, human adipose tissue may be more appealing to remove for most compared to bone marrow.  Adipose-Derived Stem/Stromal Cells (ADSC) can differentiate to ligaments, tendon, muscle, cartilage, bone or fat.  Fat grafting is common in cosmetic procedures and this lipoaspirate is now being used in musculoskeletal pain management either with or without PRP to stimulate the growth of new cells as well as stimulate the growth of cells already present in the joint area. ADSC are similar but not identical to bone marrow cells.  

Lipoaspirates are an abundant stem cell source with a tremendous therapeutic potential for the repair and regeneration of acute and chronically damaged musculoskeletal tissues. Adipose (fat) stem cells can be retrieved in high numbers from liposuction aspirates and then used as the proliferant for Stem Cell Prolotherapy. Lipoaspirates can be combined with other proliferants including platelet rich plasma and bone marrow concentrates, for instance, to augment the healing effect of Prolotherapy. As with other types of Prolotherapy, injecting the proliferants into the correct area(s) is the major determinant in healing. Injections must be provided to the area(s) that are the the pain generators.

ADSC have been used with PRP and/or BMAC in the treatment of many musculoskeletal  disorders. Because of the increased simplicity of fat harvesting versus bone marrow aspiration, the use of autologous adipose tissue is gaining popularity for office use. Also, the yield of stem cells from adipose tissue is 500 to 1,000 times higher than with bone marrow.

Fat harvesting for Adipose Derived Stem Cells (ADSC) therapy is done with a very simple process called lipoaspiration. Lipoaspiration is very different from liposuction. Liposuction is performed by a plastic surgeon in an operating room using general anesthesia or sedation. Liposuction removes a very large volume of fat for cosmetic reasons while lipoaspiration  removes a very small amount of fat (10 – 20cc), and does not render any visible change in appearance. Instead of general anesthesia, lipoaspiration uses a small amount of local anesthetic and a small instrument similar to a hypodermic needle The fat is then concentrated using a simple, sterile gravity method. The lipoaspiration procedure is painless and can be performed in less than ten minutes.

Lipoaspirate Prolotherapy is a form of stem cell therapy that uses a person’s own fat cells by itself or occassionally with PRP and/or bone marrow as the primary proliferant in the Prolotherapy solution. It is a short and painless procedure with very low morbidity which is often performed with only local anesthesia .

Summary

In Stem Cell Prolotherapy, the formula then is autologous tissue either from adipose (ones’ own fat) and/or bone marrow and/or PRP. If the fat is used, this is called “Lipoaspirate Prolotherapy” because the procedure used to obtain the fat is a type of liposuction.  If the bone marrow is the formula, the term used is “Bone Marrow Prolotherapy”.  Both are forms of Stem Cell Prolotherapy.  With Stem Cell Prolotherapy cells are not manipulated, and no additives are used.  The cells are taken from the same patient and put back in the same patient on the same day in the same procedure.

Dr Jose Veliz MD performs Stem Cell Prolotherapy at Palomar Pain Management Center which is located in San Diego County. Dr. Veliz is a member in good standing of the International Cellular Medicine Society.

Bibliography

1. Veronesi F, Giavaresi G, Tchon M, Borsari V, Nicoli Aldini N, Fini M. Clinical Use of Bone Marrow, Bone Marrow Concentrate, and Expanded Bone Marrow Mesenchymal Stem Cells in Cartilage Disease.Stem Cells Dev. 2012 Nov 16.

2. Chen FH, Tuan RS. Mesenchymal stem cells in arthritic diseases.Arthritis Res Ther 2008, 10:223.

3. Zuk PA. The Adipose-derived stem cell: looking back and looking ahead. Mol Biol Cell. 2010; 21(11): 1783-1787.

4. Caplan A. Mesenchymal stem cells. J Orthop Res. 1991; 9(5):641-650.

5. Izadpanah R, Trygg C, Patel B, et al. Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue. J Cell Biochem. 2006;99(5): 1285-1297.

6. Wakitani S, Imoto K, Yamamoto T, Salto M, Murata N, Yoneda M. Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthrits Cartilage. 2002;10(3):199-206.

7. Mizuno H. Adipose-derived stem cells for tissue repair and regeneration: ten years of research and a literature review. J Nippon Med Sch. 2009:76(2):56-66.

Kyphoplasty

kyphoplasty

Spinal Cord Stimulation

spinal stimulator

Facet Joint Injections

facet joint injection

Epidural Nerve Block

epidural nerve block

Radiofrequency

radiofrequencyablation