Mesenchymal stem cells | EBSCO Research Starters

Treatment

Also known as: Bone marrow stromal stem cells, multipotent stromal cells

Anatomy or system affected: Arms, bones, cells, circulatory system, feet, hands, immune system, joints, knees, legs, ligaments, muscles, musculoskeletal system, spine, tendons

Definition: A self-renewing population of multipotent stem cells present in bone marrow and many other adult tissues.

bone marrow: the soft, highly vascular, fatty tissue inside most bone cavities, which is the source of red and white blood cells

bone marrow aspirate: the removal of a small quantity of bone marrow through a needle

cytokines: small proteins secreted by immune cells that affect cell activity and inflammation

fluoroscope: an instrument that can visualize the form and motion of the deep structures of the body by means of X-ray shadows projected on a fluorescent screen

meniscus: the crescent-shaped cartilage pads between the bottom of the thighbone (femur) and the top of the shinbone (tibia)

multipotent: the ability of particular progenitor cells to differentiate into multiple, but limited cell types

stem cells: undifferentiated cells from a multicellular organism that can self-renew and whose progeny can differentiate into other cell types

Mesenchymal stem cells (MSCs) are multipotent stem cells that have the ability to differentiate into bone-making cells (osteoblasts), cartilage-making cells (chondrocytes), and fat-making cells (adipocytes). They are found in bone marrow (although MSCs constitute only 0.0010.01 percent of total cells), fat, umbilical cord, muscle, connective tissue skin, and several other tissues. When grown in culture, MSCs adhere to plastic, are spindle-shaped, and express specific cell-surface proteins (CD73, CD90, and CD105).

Because of the ability of MSCs to make cartilage and bone, physicians have used them to treat joint problems that affect the knee, hip, shoulder, back, hand, and ankle, and nonunion fractures. MSC-based treatments begin with the isolation of bone marrow cells from a bone marrow aspirate. This aspirate is collected from the crest of the ilium of the pelvis with an elongated hollow alignment needle, after which the bone marrow stem cells are concentrated in the laboratory through centrifugation. After concentration, these stem cells are re-injected into the injured area in combination with growth factors from blood platelets taken from peripheral blood. The stem cell injections are not done blindly. Magnetic resonance images (MRIs) of the joint show exactly where the stem cells should go and the injections themselves are guided by means of real-time fluoroscopy or musculoskeletal ultrasound. By placing MSCs directly at the site of the injury, the MSCs can replace damaged cartilage or heal partially torn tendons.

Fat-derived MSCs and associated fat cells (adipocytes) are also being used in plastic surgery to treat facial, breast, and body contour deformities for both reconstructive and aesthetic purposes. Fat for plastic surgery is harvested by means of liposuction and processed by centrifugation. The processed fat is then injected into the desired space.

For orthopedic purposes, MSCs can be used to treat osteoarthritis of the knees, hips, shoulders, ankles, and hands. They can also be used to treat partially, but not completely, torn, ligaments, meniscus tears of the knee, and labrum tears and rotator cuff injuries of the shoulder. Generally, MSC administration causes few side effects. Swelling and pain at the site of injection and discomfort from the bone marrow aspiration are some of the most common side effects. Also, if MSCs donated by someone else are injected, there is the possibility that the patient's immune system might reject them. Tumor formation as a result of MSC treatment has not been observed in humans.

Fat-based MSCs and adipocytes for plastic surgery are used to reestablish body contours after injury, surgery, or disease, or to reconstruct the face after an accident or corrective surgery or the breasts after mastectomies. For aesthetic treatments, fat transplantations can remove wrinkles, augment the size of the breast or buttocks, or create new body contours. Complications associated with fat transplantation include infections, and if the fat-based MSCs are mixed with the wrong materials, they can form ectopic bone. Fat transplantation into the breast can cause lumps that calcify. Also, the death of transplanted fat cells (fat necrosis) can produce small calcifications and palpable lumps, which can increase the opacity of the breast and interfere with mammographic scans. No evidence exists to support the concern that transplanting fat into the breast increases the risk of breast cancer, but animal experiments suggest that MSCs can augment the growth of preexisting tumors.

Because MSCs have the ability to suppress the function of immune cells and inflammation through the secretion of cytokines, they have been used to treat autoimmune diseases on an experimental basis. Autoimmune diseases result from an inappropriate immune response against normal cells. Such diseases as Crohn's disease, multiple sclerosis, systemic lupus erythematosis, scleroderma, and graft-versus-host disease have all been treated experimentally with MSCs administered either intravenously or injected directly into damaged tissues. The rationale behind the use of MSCs to treat these diseases, which are characterized by chronic inflammation, is to suppress inflammation so that the damaged tissues and organs can heal and regain their normal level of function.

Experiments that demonstrated the bone-making capacity of bone-free bone marrow date from the nineteenth century; Tavassoli and Crosby in 1968 and Friedenstein and others in the 1960s and 70s confirmed these results and showed that a bone marrow stem cell population distinct from blood-making stem cells synthesized bone.

Many clinical trials to evaluate the safety and efficacy of MSC treatments are underway. In such trials, MSCs have been used to treat liver disease, fragile bone disease (osteogenesis imperfecta), heart disease, and several other maladies. Genetically engineered MSCs have also been successfully tested in animal models and show remarkable healing potential. MSCs presently represent one of the most fruitful areas of medical research.

Buratovich, Michael A. The Stem Cell Epistles: Letters to My Students about Bioethics, Stem Cells, and Fertility Treatments. Eugene: Cascade, 2013. Print.

Centeno, Christopher J., and Stephen J. Faulkner. The Use of Mesenchymal Stem Cells in Orthopedics. Stem Cells and Cancer Stem Cells. Vol. 1. Ed. M. A. Hayat. New York: Springer, 2012. Print.

Jones, Elena, Peter Giannoudis, Xuebin Yang, and Dennis McGonagle. Mesenchymal Stem Cells and Skeletal Regeneration. Waltham: Academic, 2013. Print.

Rosing, James H., Granger Wong, Michael S. Wong, David Sahar, Thomas R. Stevenson, and Lee L. Q. Pu. Autologous Fat Grafting for Primary Breast Augmentation: A Systematic Review. Aesthetic Plastic Surgery 35 (2011): 88290. Print.

"Stem Cell Basics: What Are Adult Stem Cells?" Stem Cell Information. Natl. Inst. of Health, 3 Mar. 2015. Web. 18 Mar. 2015.

Turksen, Kursad. Stem Cells: Curernt Challenges and New Directions. New York: Humana, 2013. Print.

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Mesenchymal stem cells | EBSCO Research Starters