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Stem cells help to create new cells in existing healthy tissues, and may help repair tissues in areas that are injured or damaged. They are the basis for the specific cell types that make up each organ in the body.
Stem cells are distinguished from other cells by a few important characteristics: they have the ability to self-renew; they have the ability to divide for a long period of time; and, under certain conditions, they can be induced to differentiate into specialized cells with distinct functions (phenotypes) including, but not limited to, cardiac cells, liver cells, fat cells, bone cells, cartilage cells, nerve cells, and connective tissue cells. The ability of cells to differentiate into a variety of other cells is termed multipotency.
What scientists learn about controlling stem cell differentiation can become the basis for new treatments of many serious diseases and injuries.
Scientists primarily work with two main types of stem cells: adult stem cells and embryonic stem cells. Adult stem cells are used in research for orthopaedic conditions.
Embryonic stem cells are more basic cells obtained in the laboratory. Unlike adult stem cells, which are obtained from living human tissue, embryonic stem cells are removed from human embryos that have been fertilized in the laboratory or in vitro. They are typically removed 4 to 5 days after fertilization and then grown in culture.
Embryonic cells are pluripotent and can develop into almost any type of cell in the body. Adult stem cells are more tissue-specific and are therefore more useful to orthopaedic surgeons who are attempting to repair bone, muscle, and cartilage. Orthopaedic surgeons who use cell therapy typically work with adult stem cells.
The most common (and probably the most studied) source for adult stem cells is the bone marrow, which contains two types: hematopoietic (blood forming cells) and mesenchymal stem cells. Of particular interest in orthopaedic research are bone marrow stromal cells. These are mesenchymal stem cells that, in the proper environment, can differentiate into cells that are part of the musculoskeletal system. They can help to form trabecular bone, tendon, articular cartilage, ligaments, and part of the bone marrow.
Researchers in the last 10 years have reported the presence of adult stem cells in several other tissues aside from bone marrow, including the brain, hair follicles, dental pulp, skin, liver, skeletal muscle, blood vessel walls, pancreas, and intestine.
Another stem cell that has been studied recently is the cancer stem cell. Researchers believe that a stem cell proliferates to give rise to tumors in a growing list of cancers. Such cells regenerate the tumor after cycles of cancer therapy and surgery. Comparative studies of the signaling pathways of normal and cancer stem cells could provide information on what specific molecules can be targeted to screen for and to prevent the formation of cancers.
Adult stem cells are most commonly obtained from the outside part of the pelvis, the iliac crest. A needle is inserted in the iliac bone and bone marrow is withdrawn or aspirated through the needle. Several samples may be obtained from one area in this manner.
The stem cells may then be separated from other cells in the marrow and grown or expanded in the laboratory. This may take from 7 to 21 days.
When stem cells are placed in a specific tissue environment, such as bone, they become activated. As they divide, they create new stem cells and second generation, progenitor cells. It is the progenitor cells which may differentiate into newer cells with the same phenotype as the host tissue.
Stem cell researchers are hopeful that, in the future, a wide range of diseases and traumatic injuries will be cured by some application of cell therapy using stem cells.
Currently, donated organs and tissues are used to replace lost or damaged tissue in many disorders. The great regenerative potential of stem cells has created intense research involving experiments aimed at replacing tissues to treat Parkinson's and Alzheimer's diseases, osteoarthritis, rheumatoid arthritis, spinal cord injury, stroke, burns, heart disease, and diabetes.
While some success has been achieved with laboratory animals, a very limited number of experiments have been conducted on humans. These few experiments, however, have shown the great potential for stem cells. Scientists believe that a deep understanding of the complex phenomenon of stem cell differentiation will lead to a potential cure for serious medical conditions that are caused by abnormal cell division and differentiation, such as cancer and several growth and development disorders.
Another reason why stem cell biologists are excited about this field is that human stem cells could also be used to test new drugs. For example, new medications could be tested for safety by applying them to specialized cells differentiated from a stem cell clone. Cancer treatment, for instance, could benefit tremendously if anti-tumor drugs could be tailored to target the tumor stem cell.
At this point, most musculoskeletal treatments using stem cells are performed at research centers as part of controlled clinical trials. Stem cell procedures are being developed to treat bone fractures and nonunions, regenerate articular cartilage in arthritic joints, and heal ligaments or tendons. These are detailed below.
Bone fractures and nonunions: In bone, progenitor cells may give rise to osteoblasts, which become mature bone cells, or osteocytes. Osteocytes are the living cells in mature bone tissue. Stem cells may stimulate bone growth and promote healing of injured bone.
Traditionally, bone defects have been treated with solid bone graft material placed at the site of the fracture or nonunion. Stem cells and progenitor cells are now placed along with the bone graft to stimulate and speed the healing.
Articular cartilage: The lining of joints is called the articular cartilage. Damage to the articular cartilage can frequently lead to degeneration of the joint and painful arthritis. Current techniques to treat articular cartilage damage use grafting and transplantation of cartilage to fill the defects. It is hoped that stem cells will create growth of primary hyaline cartilage to restore the normal joint surface.
Ligaments and tendons: Mesenchymal stem cells may also develop into cells that are specific for connective tissue. This would allow faster healing of ligament and tendon injuries, such as quadriceps or Achilles tendon ruptures. In this instance, stem cells would be included as part of a primary repair process.
In a recently reported Canadian study, stem cell therapy was successfully used to treat urinary incontinence in 25 patients.
Treatment involved injecting muscle stem cells into the neck of the urinary bladder to strengthen the weak valve. Most interestingly, the stem cells utilized were the patients' own cells (autologous) obtained from biopsies of the skeletal muscle from their arms.
It is noteworthy that the research used to furnish data for this therapy came from several years of work examining the potential uses of muscle-derived stem cells in treating musculoskeletal disease.
Musculoskeletal stem cell researchers are conducting numerous studies.
One recent study examined the ability of muscle-derived stem cells to repair articular cartilage and promote restoration.
Drs. Kuroda and Huard (University of Pittsburgh) and their team cultured muscle stem cells derived from newborn mice for two weeks and mixed them with fibrin glue. When applied to cartilage defects in 12-week-old athymic rats, the genetically engineered cells enhanced new cartilage formation and improved articular cartilage repair.
Dr. Lieberman (UCLA) conducted a similar study, which showed that using genetically engineered bone marrow cells from rats can significantly help heal large leg bone defects in rats.
The results of studies like these provide proof-of-concept that such methods could be used to treat osteoarthritis, nonunion fractures, and bone defects in humans.
Stem cells for cell therapies are still in the experimental phases for several diseases, conditions, and disabilities, including Type 1 diabetes (diabetes mellitus); Parkinson's and Alzheimer's diseases; muscle disorders, including dystrophies like Duchenne and Becker; multiple sclerosis; spinal cord injuries; ischemic brain strokes; burns; heart disease; osteoarthritis; and, rheumatoid arthritis.
Moreover, cancer therapy and detection is likely to be revolutionized by advances and greater understanding gained through stem cell science.
Another area that holds great promise for the future is the area of in utero stem cell therapy for congenital, hematological, metabolic, and immunological disorders. For many of these diseases, early intrauterine management is an ideal choice, as the immune system has not completely developed.
The American Academy of Orthopaedic Surgeons
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