lipid and glucose metabolism, serves as a storage depot for free fatty acids, and produces many cytokines and hormones involved in normal physiologic metabolism and pathologies, including lipodystrophy, obesity, diabetes mellitus, vascular disease, and metabolic syndrome. Understanding adipose tissue function and pathology can help to advance research and development for the management and prevention of human disease.
Krishna S. Vyas
Amanda Blau
University of Kentucky College of Medicine
See Also: Adipose: Cell Types Composing the Tissue; Adipose: Development and Regeneration Potential; Adipose: Stem and Progenitor Cells in Adults; Adipose: Tissue Function.
Further Readings
Berg, A. H. and P. Scherer. “Adipose Tissue, Inflammation, and Cardiovascular Disease.” Circulation Research, v.96/9 (2005).
Harjer, G. R., T. W. van Haeften, and F. L. J. Visseren. “Adipose Tissue Dysfunction in Obesity, Diabetes, and Vascular Disease.” European Heart Journal, v.29 (2008).
Payne, V. A., N. Grimsey, A. Tuthill, S. Virtue, S. L. Gray, E. D. Nora, and J. J. Rochford. “The Human Lipodystrophy Gene BSCL2/Seipin May Be Essential for Normal Adipocyte Differentiation.” Diabetes, v.57 (2008).
Adipose: Stem and Progenitor Cells in Adults
Adipose: Stem and Progenitor Cells in Adults
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Adipose: Stem and Progenitor Cells in Adults
Adipose tissues play major roles in storage and active regulation of metabolism. In addition to these functions, adipose tissue has properties that give it potential application for tissue regeneration or transfer. Adipose may be a source of unique, pluripotent (possessing the ability to form into cells originating from any of the three germ layers: ectoderm, mesoderm, endoderm) stem cells. The utilization of stem cells and cytokines can lead to tissue repair and the regeneration of damaged tissues. Other multipotent (possessing the ability to differentiate into multiple but limited cell types) progenitor cells can be drawn in an undifferentiated state. Progenitor cells are considered to have already committed to differentiation on a specific cellular pathway. There may be fewer political, legal, and ethical issues with adipose stem and progenitor cells as compared to embryonic stem cell use.
Multi-Lineage Potential
Stem cells must have the ability to continually divide (self-renewal), maintain viability long term, and have the potential to differentiate. Stem cells extracted from bone marrow (mesenchymal stem cells) have shown multi-lineage potential through extensive study and have been suggested as alternatives to embryonic stem cells in mesodermal defect repair and disease management. However, issues with pain, morbidity, and low cell number during extraction impede the practical use of bone marrow stem cells.
Like stems cells derived from bone marrow, adipose tissue is of mesodermal origin. Adipose-derived stem cells (ADSCs) can differentiate in vitro (isolated studies in experimental biology) toward osteogenic (bone), adipogenic (fat), myogenic (muscle), and chondrogenic (connective tissue) lineages when treated with established lineage-specific factors. Studies have shown that ADSCs show lineage-specific genes to distinctive cell lines such as osteocytes or myocytes when stimulated to develop into different cells.
ADSCs can differentiate into adipocytes, chondrocytes, and osteoblasts, a feature known as multipotency. A single ADSC is also capable of cloning itself and then further differentiating into multiple lineages, a capacity known as clonogenicity. For example, human ADSCs show in vitro evidence of differentiation along myocyte lineage pathways. When cultured with myocyte lineage factors, adipocytes fuse and express protein markers of skeletal myocyte lineage. This suggests that these cells have the potential to repair damaged skeletal muscle. ADSCs can also differentiate into osteoblast-like cells by depositing calcium phosphate mineral into their extracellular matrix and expressing osteogenic genes and proteins. Evidence suggests that these cells have the potential to accelerate repair at fracture sites.
The range of differentiation that ADSCs possess extends beyond bone, muscle, and connective tissue. There may be possibility of repairing gastrointestinal and urinary tract smooth muscle defects with ADSCs. Factors can also differentiate these cells along the cardiac myocyte pathway and may be a source of regeneration for cardiac tissues damaged from infarction or ischemic injury. Preliminary studies have also implicated ADSCs in the regeneration of the central and peripheral nervous system following traumatic injury.
Adhesion proteins associated with hematopoietic stem cells can form on ADSCs, which can also secrete cytokines (substances secreted by cells of the immune system) and promote differentiation along the B-cell, T-cell, and myeloid (white blood cell) lineages. This possible application can extend to conditions that weaken patients’ immune systems such as those patients undergoing high-dose chemotherapy or suffering from inborn errors of metabolisms.
Harvesting Adipose-Derived Stem Cells
Adipose tissue is an exciting resource for tissue regeneration and soft tissue repair because it houses one of the richest reservoirs of stem cells in the human body. Thus, stem cells collected from adipose tissue do not need to be cultured in order to obtain a therapeutically vital number of cells. Well-nourished humans store excess calories in adipose tissue that increase cell volume and expansion of the number of differentiated adipose cells, suggesting that adipose tissue progenitor cells exist within adult fat tissue. ADSCs can also be harvested easily with little harm to the patient through the process of liposuction, making adipose stem and progenitor cells much more accessible than bone marrow cells. ADSCs cultured in vitro have shown consistent profiles of cell-surface proteins, which include adhesion proteins, receptor molecules, surface enzymes, extra-cellular matrix proteins and glycoproteins, skeletal proteins, hematopoietic (involved in blood formation) cell markers, complement regulatory proteins, and histocompatibility antigens (immune system components).
Diagram showing stem cells and progenitor cells. Stem cells are undifferentiated biological cells that can differentiate into specialized cells that can replicate indefinitely to produce more stem cells. A progenitor cell has a tendency to differentiate into a specific type of cell—its “target” cell. (Wikimedia Commons)
The immunophenotype of ADSCs resemble other adult stem cells from bone marrow and skeletal muscle. Methods of harvesting the tissue have dramatic effects on the ability of the cells to proliferate and differentiate in culture. Several studies report a negative correlation between patient age and the yield of donor cells and proliferation. Many concerns remain for the standardization and optimization of methods for cell isolation, culture, and application.
Future Development
ADSCs may prove to be an ideal option for tissue engineering in regenerative medicine since they are self-renewable, plentiful, and easily accessible through minimally invasive procedures. Studies suggest that ADSCs can be used in the treatment of type 1 diabetes mellitus, obesity, cardiovascular disease, lipodystrophy, and neurodegenerative diseases. For example, ADSCs have the ability to be carriers for gene delivery vehicles through transduction, the process by which foreign DNA is introduced into another
