The SAGE Encyclopedia of Stem Cell Research. Группа авторов
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.
Further Readings
Gir, P., et al. “Human Adipose Stem Cells: Current Clinical Applications.” Plastic and Reconstructive Surgery, v.129/6 (2012).
Lindroos, B., et al. “The Potential of Adipose Stem Cells in Regenerative Medicine.” Stem Cell Review, v.7/2 (2011).
Tobita, M., et al. “Adipose-Derived Stem Cells: Current Findings and Future Perspectives.” Discovery Medicine, v.11/7 (2011).
Zhu, Y., et al. “Adipose-Derived Stem Cell: A Better Stem Cell Than BMSC.” Cell Biochemistry and Function, v.26/6 (2008).
Adipose: Major Pathologies
Adipose: Major Pathologies
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Adipose: Major Pathologies
Adipose tissue consists of adipocytes, a dynamic and highly regulated population of cells, and a stromal vascular fraction, which includes preadipocytes. Adipogenesis results in the generation of adipocytes from preadipocytes, which arise from a multipotent stem cell of mesodermal origin. This article focuses on stem cells as they relate to adipogenesis and how the dysfunction of adipogenesis is responsible for the role of adipose cells in the development of pathology.
Lipodystrophy
Patients with lipodystrophy have a variable lack of adipose tissue, with the severity of the pathology being determined by the magnitude of fat absence. Lipodystrophies are categorized as genetic or inherited. Genetic lipodystrophies are monogenetic disorders caused by mutations in a gene. Inherited lipodystrophies have several identified genes as a cause, with congenital generalized lipodystrophy and familial partial lipodystrophy being the two main subtypes. Some of these mutations responsible for these diseases code for genes in pathways involved in the development of multipotent mesodermal stem cells to preadipocytes, as well as for the differentiation of these preadipocytes to adipocytes. Consequently, failed adipogenesis from stem cells can be responsible for the development of this disease in some cases. This lack of adipose tissue, due to failure of adipogenesis or another cause, results in inadequate storage of free fatty acids (FFA), which results in increased circulation of FFA and lipotoxicity. Lipotoxicity is characterized by ectopic fat deposition in non-adipose cells, including the pancreas. Ectopic deposition contributes to insulin resistance and deposition in the pancreas creates beta cell dysfunction; these two conditions are necessary for the development of type 2 diabetes mellitus.
Obesity
During positive caloric balance, adipocytes initially undergo hypertrophy. The body’s appropriate response to this is to trigger adipogenesis, which allows for the generation of additional fat cells. This maintains normal adipose tissue physiologic function while increasing the body’s energy stores. However, if this adipogenesis is impaired, the hypertrophied adipocytes have pathogenic potential due to the resulting adipose tissue dysfunction. This leads to a state of hypersecretion of pro-artherogenic, pro-inflammatory, and pro-diabetic adipocytokines, which is accompanied by a decreased production of adiponectin, a protein involved in the regulation of glucose levels as well as fatty acid breakdown. Therefore, obesity can cause adipose tissue dysfunction, but not all obese individuals have a loss of adipose tissue architecture and function. The dysfunction depends on the failure of adipogenesis and the ensuing hypertrophy of the cells.
Hypertrophied adipocytes tend to expand to have a diameter that is greater than the diffusion limit of oxygen. This leads to hypoxia-induced expression of transcription factors prompting angiogenic factor expression. This decreases the adiponectin promoter and PPARg activity, reducing the stability of adiponectin mRNA, and decreasing adiponectin expression. At the same time, leptin and PA-1 gene transcription is induced in adipose tissue.
Leptin is one of the most important adipose-derived