Stem Cell Therapy

Stem cell prolotherapy is the most exciting addition to the regenerative medicine field of Prolotherapy.  A person’s healing cells are obtained from bone marrow, fat, and blood (in various combinations or alone) and then injected into the area with 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 stimulate the repair of injured tissues. However, they are both dependent on the body having enough 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.  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 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 in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans.

Stem cell prolotherapy assists in fibroblastic proliferation and chondrocyte proliferation. In stem cell prolotherapy, the tissues being targeted to stimulate to repair can include articular cartilage besides 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 using 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. Using minimally manipulated autologous stem cells for orthopedic conditions is FDA-cleared. Using MSC’s is legal and safe.

MSC’s can be harvested and injected into our own degenerated joints and ligaments. These cells upon contact with damage joint surfaces or other damaged tissue can 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 creating 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:

  • lower back pain,
  • joint osteoarthritis,
  • shoulder pain,
  • joint pain,
  • hip pain, and
  • 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 can become tissues like cartilage, bone, and ligaments.

The concentration of the bone marrow is an important element of efficacy, and there are FDA approved devices which concentrate the bone marrow into “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) differs 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 small amount of bone marrow. The BMAC procedure is not painful and causes only mild soreness after completion. This procedure takes ten minutes or less and has an outstanding safety profile with 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 comprises are called chondrocytes. BMAC’s proposed mechanisms include

  • reducing the joint instability that originally led to the degenerative arthritis,
  • stimulating the growth of new cells that create the extracellular matrix causing the chronic pain and/or instability,
  • stimulating the cells already present to make an extracellular matrix, and
  • injected precursor cells (stem cells) differentiating 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 into 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 and 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 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 of healing. Injections must be provided to the area(s) that are 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, using 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 differs greatly 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 small amount of fat (10 – 20cc), and renders no visible change in appearance.

Instead of general anesthesia, lipoaspiration uses a little 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 fat cells by itself or occasionally with PRP and/or bone marrow as the primary proliferant in the prolotherapy solution. It is a short and painless procedure with low morbidity often performed with only local anesthesia.

Summary

In stem cell prolotherapy, the formula then is autologous tissue either from adipose (ones’ 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.

Jose Veliz MD is the medical director of Palomar Spine & Pain, in Escondido, CA (North San Diego County). Dr. Veliz is a member in good standing of the International Cellular Medicine Society.


Bibliography

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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.

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