Читать книгу The SAGE Encyclopedia of Stem Cell Research - Группа авторов - Страница 63

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Adipose: Existing or Potential Regenerative Medicine Strategies

A stem cell is a cell that has the ability to self-renew and differentiate into one or more types of cells. Therefore, stem cells hold great promise for regeneration and repair of tissues. Recent study has focused on their use for the treatment of Parkinson disease, Alzheimer disease, cancer, myocardial infarction injuries, breast reconstruction, diabetes mellitus, autoimmune diseases, and much more. Unlike the embryologic stem cells that aroused much controversy, adipose-derived stem cells (ASCs) are derived from adults and are noncontroversial. Furthermore, research suggests ASCs are a better stem cell source than the conventional mesenchymal stem cells—the bone marrow stem cells (BMSCs).

Shift From BMSCs to the ASCs

Historically, BMSCs were the most frequently used mesenchymal stem cell pool. However, ASCs are more advantageous in several respects. The pool of ASCs is larger than that of BMSCs. They can be collected by liposuction with local anesthesia, whereas bone marrow acquisition is more invasive, requires general anesthesia, and carries a greater risk for mortality. Furthermore, clinical data show that ASCs have a higher proliferation rate than BMSCs. ASCs can grow to 90 percent confluence within three days compared to BMSCs, which can take a week to reach the same mark.

Potential of ASCs

ASCs are multipotent and mesenchymal in origin. Initially, ASCs were studied for differentiation into chondrogenic, myogenic, and osteogenic cell types. However, further research showed transdifferentiation capacity extending beyond the traditional mesenchymal lineage. ASCs are now known to be capable of skeletal myogenesis, cardiac myogenesis, neurogenesis, and angiogenesis.

ASC use in regenerative therapy involves redirection from normal reparative function to generation of new tissue in areas that are diseased or received trauma. In addition to their proliferative capacity, ASCs also decrease inflammation and release growth factors, allowing focused healing. Their anti-inflammatory nature suggests potential for treating autoimmune and inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, and graft-versus-host disease.

Clinical Applications and Published Clinical Trials

ASC therapy is gaining popularity. Most studies report no adverse effects and the majority of outcomes were beneficial. However, rigorous trials are lacking and most publications are case reports and noncontrolled studies.

The clinical applications of ASCs discussed in this article are spinal cord injury; diabetes mellitus; breast reconstruction and augmentation; facial lipoatrophy; rheumatoid arthritis; multiple sclerosis; hematologic and immunologic disorders; complex perianal or enterocutaneous fistulas and tracheomediastinal fistula; bone tissue repair; cardiovascular disease; cancer; and musculoskeletal regeneration.

Spinal Cord Injury

Stem cells have been studied intensely for spinal cord injury because the damaged axons and neurotransmitter-producing neurons cannot be regenerated by the human body. As a result, individuals with spinal cord injury suffer loss of sensory and motor function below the site of injury. Scientists started working with stem cells with the hope that they would promote new regeneration of neurons to promote healing. Indeed, in 2011, eight patients with spinal cord injury who were treated with intravenous infusions of autologous ASCs were shown to have improved motor function after 12 weeks.

Type 1 Diabetes Mellitus

Type 1 diabetes mellitus occurs because of autoimmune attack on pancreatic cells. The number of beta islet cells is reduced as a result, leading to decrease in insulin and C-peptide production. ASCs were studied for their ability to regenerate pancreatic beta islet cells. In a study of ASC therapy administered to five patients with diabetes, results showed a 30% to 50% decrease in insulin requirements and increase in serum C-peptide levels during a follow-up period of 2.9 months. No adverse effects were noted.

Breast Reconstruction and Augmentation and Facial Lipoatrophy

It should come as no surprise that ASCs have the potential for adipose tissue regeneration. In 2008, ASCs were used successfully for breast augmentation. Normally, the body resorbs injections of unprocessed adipose tissues. However, when patients were injected with a mixture of ASCs and unprocessed adipose tissue, they retained the volume over the next 12 months. Similar success was shown in facial lipoatrophy.

Autoimmune Diseases

ASCs have potential for treatment of autoimmune diseases. In 2010, there was a case report of ASC use in a 67-year-old woman with rheumatoid arthritis. She was treated with autologous ASCs isolated from liposuction; subsequently, she reported reduced joint pain and stiffness. Additionally, authors measured the levels of rheumatoid factor as a more objective measurement and noted a decrease after treatment. The patient had no side effects.

ASCs have also been used for the treatment of multiple sclerosis, another autoimmune disease. Three patients with multiple sclerosis received intravenous infusions of ASCs, allogeneic CD34+ cells, and mesenchymal cells. Patients reported significant improvement of symptoms.

Hematologic and Immunologic Disorders

Researchers have also studied ASCs for the treatment of graft-versus-host disease, idiopathic thrombocytopenic purpura, and pure red-cell aplasia. Patients were given intravenous infusion of allogeneic ASCs. Treatment was successful in graft-versus-host disease and pure red-cell aplasia; in idiopathic thrombocytopenic purpura, remission was achieved. However, the effect of ASCs on alloreactivity in patients who have undergone solid-organ transplantation is not yet known.

Fistulas

Potential use of ASCs for fistulas has been demonstrated in treatment of perianal, enterocutaneous, and tracheomediastinal fistulas. To study the effect of ASCs on perianal and enterocutaneous fistulas, the fistulas of the patients were injected with autologous ASCs mixed with proteinaceous fibrin glue. Results of phase 1 and 2 clinical trials showed four times the healing compared to the control group. Again, no adverse effects were reported.

To study the effect of ASCs on a patient with lung cancer-induced tracheomediastinal fistula, the patient’s fistula was injected with autologous ASCs mixed with fibrin glue. Epithelialization of the fistula was observed three months later and was completely closed one year after treatment. This case is particularly encouraging, as fistula progression into blood vessels occurs frequently and is often fatal. No side effect was noted.

Bone Tissue Repair

In 2004, there was a case report on a seven-year-old girl who had a calvarial defect from a severe head injury. The first attempt at treatment, fixation of calvarial fragments via titanium miniplates, was unsuccessful. She was then treated with a mixture of autologous ASCs and autologous bone from the iliac crest. Three months after the surgery, computed tomography scan confirmed successful calvarial bone formation.

Cardiovascular Diseases and Cancer

Not all studies with ASCs have shown positive results. Study of ASCs for treatment of acute myocardial infarction and cancer are two examples where results have been inconsistent.

Musculoskeletal Regeneration (Clinical Study on Animal Models)

Musculoskeletal regeneration is an area of intense research because there is a limited pool of muscle progenitor cells, called satellite cells. Therefore, ASCs were used as a potential therapy for muscular disorders. In 2006, intravenous injection of allogeneic ASCs was shown to restore muscle function in murine muscular dystrophy. Successful use of ASCs in intervertebral disc regeneration has been also reported. In addition, topical administration of adipose stem cells on rabbits’ tendons accelerated tendon repair rate and tensile strength was increased, supporting the transdifferentiation potential of the ASCs in vivo and in vitro.

Conclusion

Though their effectiveness is still unproven, treatment with ASCs in regenerative medicine appears promising. However, their benefit in the treatment of cancer is particularly weak and presents a major concern, since ASCs secrete cytokines that may affect cancer metastases. More research is needed for conclusive evidence, and further work will be required to determine the safety of ASCs.

Likewise, standard protocols for ASC studies do not exist yet. The ideal procedure for acquiring ASCs, the optimal number of stem cells that should be used for each procedure, and the safe number of stem cells that can be injected into different organs will have to be determined.

Krishna S. Vyas

Kristine Song

University of Kentucky College of Medicine

See Also: Adipose: Development and Regeneration Potential; Bone: Existing or Potential Regenerative Medicine Strategies; Pancreatic Islet Transplant; Spinal Cord Injury.