cardiac troponin-I, spontaneous beating, and cell morphology (binucleated, striated cells). While transplantation of ASCs may improve cardiac function by differentiating and replenishing injured or lost myocytes, no studies have been evaluated in vivo.
The Future of ASCs
Deriving stem cells from adipose tissue has proven to be an efficacious, safe, and simple process with little donor site morbidity. Furthermore, stem cell yields from adipose tissue are far greater than most stem cell reservoirs in the human body. While they may be suitable candidates in regenerative medicine, various limitations still remain. One of the major concerns with the use of ASCs is that very few in vivo clinical trials have been conducted compared to the large number of in vitro preclinical studies. In addition, many scientific questions remain unclear. Firstly, the specific transcription factors and key molecular events that allocate ASCs to a particular lineage have not been identified. Secondly, evidence implies that the ability for ASCs to differentiate may depend on the anatomic source and the donor’s age and gender. Furthermore, methods for large-scale manufacturing with appropriate quality control and quality assurance have yet to be developed. To fulfill expectations and to determine if ASC-based therapies can be successfully implemented in treatment, further investigation is required.
Krishna S. Vyas
Nicholas Chien
University of Kentucky College of Medicine
See Also: Adipose: Current Research on Isolation or Production of Therapeutic Cell; Adipose: Existing or Potential Regenerative Medicine Strategies; Heart Disease; Tissue Engineering (Scaffold); Tissue Regeneration: Humans.
Further Readings
Agarwal, Anil K., and Abhimanyu Garg. “Genetic Disorders of Adipose Tissue Development, Differentiation, and Death.” Annual Review of Genomics and Human Genetics, v.7 (2006).
Gimble, Jeffrey M., Adam J. Katz, and Bruce A. Bunnel. “Adipose-Derived Stem Cells for Regenerative Medicine.” Circulation Research, v.100 (2007).
Mizuno, Hiroshi, Morkiuni Tobita, and Cagri Uysal. “Concise Review: Adipose-Derived Stem Cells as a Novel Tool for Future Regenerative Medicine.” Stem Cells, v.30 (2012).
Zachar, Vladimir, Jeppe G. Rasmussen, and Trine Fink. “Isolation and Growth of Adipose Tissue-Derived Stem Cells.” Methods in Molecular Biology, v.698 (2011).
Zuk, Patricia A., Min Zhu, Peter Ashjian, et al. “Human Adipose Tissue Is a Source of Multipotent Stem Cell.” Molecular Biology of the Cell, v.13 (2002).
Adipose: Existing or Potential Regenerative Medicine Strategies
Adipose: Existing or Potential Regenerative Medicine Strategies
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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
