T-regulatory immune cells and macrophages are resident to the SVF. The T-regulatory cells (T-regs) are immune suppressive cells formed from the activation of T cells in the absence of costimulatory signals, and their presence in adipose tissue has shown to be induced by markers generated from MSCs in adipose. T-regs in turn help promote the presence of macrophages. The macrophages present in adipose tissue are interesting in that they possess markers for both pro- and anti-inflammatory processes. On a surface level, adipose tissue macrophages (ATMs) express markers and receptors similar to M2-type macrophages, which promote tissue repair. ATMs, like M2 macrophages, can also be induced to secrete anti-inflammatory proteins like IL-10 and IL-1 receptor antagonist.
However, these same ATMs also secrete inflammatory proteins such as TNF-α, IL-1, and IL-6 in quantities high enough to offset any anti-inflammatory activity by both the ATMs and T-regs. It is postulated that the ATM protein secretion is under the regulation of adipocytes, which also secrete these inflammatory proteins themselves, and both of these processes contribute to the low-grade inflammatory state often present in obesity.
Other cells
Vascular and extracellular matrix cells that are present throughout the body are also found in adipose tissue. Similar to vasculature throughout the body, the vessels of adipose tissue consist of endothelial and smooth muscle cells. These endothelial cells include both ordinary endothelial cells like those found elsewhere and also specialized endothelial cells that appear to be able to induce preadipocyte generation. Fibroblasts also help secrete collagen and other extracellular matrix components that help form the structure of adipose tissue.
Overall, many different cells in adipose tissue have vast potential for further research investigation. Especially with the rise of obesity, there has been a much greater international interest in learning more about the components of adipose tissue and how they can be altered. In particular, MSCs and preadipocytes show promise for future use both in treating obesity and a plethora of other disorders.
Both adipocytes and components of the stromal vascular function are integral parts of adipose tissue, and understanding their functions will be a critical cornerstone of future learning.
Krishna S. Vyas
Nazeeha Jawahir
University of Kentucky College of Medicine
See Also: Adipose: Current Research on Isolation or Production of Therapeutic Cells; Adipose: Development and Regeneration Potential; Adipose: Existing or Potential Regenerative Medicine Strategies; Adipose: Major Pathologies; Adipose: Stem and Progenitor Cells in Adults; Adipose: Tissue Function.
Further Readings
Esteve, Ràfols M. “Adipose Tissue: Cell Heterogeneity and Functional Diversity.” Endocrinol Nutr (July 5, 2013).
Majka, S. M., Y. Barak, and D. J. Klemm. “Concise Review: Adipocyte Origins: Weighing the Possibilities.” Stem Cells (July 2011).
Riordan, N. H., T. E. Ichim, W. P. Min, H. Wang, F. Solano, F. Lara, M. Alfaro, J. P. Rodriguez, R. J. Harman, A. N. Patel, M. P. Murphy, R. R. Lee, and B. Minev. “Non-Expanded Adipose Stromal Vascular Fraction Cell Therapy for Multiple Sclerosis.” Journal of Translational Medicine (April 24, 2009).
Rosen, E. D. and B. M. Spiegelman. “Adipocytes as Regulators of Energy Balance and Glucose Homeostasis.” Nature (December 14, 2006).
Zeyda, M., D. Farmer, J. Todoric, O. Aszmann, M. Speiser, G. Györi, G. J. Zlabinger, and T. M. Stulnig. “Human Adipose Tissue Macrophages Are of an Anti-Inflammatory Phenotype but Capable of Excessive Pro-Inflammatory Mediator Production.” International Journal of Obesity (London) (September 2007).
Adipose: Current Research on Isolation or Production of Therapeutic Cells
Adipose: Current Research on Isolation or Production of Therapeutic Cells
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Adipose: Current Research on Isolation or Production of Therapeutic Cells
Adipose-derived stem cells, or ASCs, are a unique population of stem cells isolated from adipose tissue. These multipotent stem cells present an alternative to the widely used embryonic and hematopoietic stem cell lineages for laboratory and clinical applications in regenerative medicine. Adipose tissue is abundant in the body and exists in several forms, including bone marrow, mammary tissue, and mechanical, brown (multilocular), and white (unilocular) adipose tissues.
Traditional methods of gathering stem cells include the controversial isolation of embryonic stem cells and the painful process of procuring stem cells from bone marrow. In contrast to these methods, an efficient manner of isolating and producing reliable stem cell populations from abundant, easily accessible adipose tissue presents an appealing alternative for clinical therapeutic applications. Thus far, adipose stem cells have been shown capable of multipotent mesodermal differentiation, as well as potential endodermal and ectodermal lineages in vitro.
Evidence for Adipocyte Precursor Cells
Progressive osseous heteroplasia (POH), a pathologic condition that leads to heterotopic bone formation within subcutaneous adipose and, eventually, muscle tissue, demonstrates the presence of adipocytes, osteoblasts, and chondrocytes upon histologic examination of the resultant lesions. Pathologic evidence from this rare, autosomal-dominant, inherited genetic defect suggests that ADCs are at least capable of differentiation into the aforementioned mesodermal lineages. Along with POH, lupus and Paget disease are also known to present with calcification of subcutaneous adipose, providing further evidence for the presence of multipotent ASCs within adipose tissue. Additionally, research using ligand-induced adipogenesis for the chemotherapeutic treatment of liposarcomas suggests that these cancers may derive from a stem cell progenitor; stimulation by both long-chain fatty acids and synthetic steroid compounds induces adipocyte formation from liposarcoma-derived cells. Furthermore, radioactive tracing to measure adipocyte turnover rates in obese patients indicates a lifespan of six to 15 months for these fully differentiated adult adipocytes, a value that seems to indicate the presence of a controlled replacement mechanism of mature cells by resident stem cell–adipocyte precursors. Evaluation of individuals who have undergone rapid weight loss through either metabolic or procedural means also supports this concept: Not only do existing adipocytes increase in volume but new adipocytes emerge in a homeostatic process to maintain a relatively constant level of adipose tissue within the organism.
Origin of ASCs
Adipose tissue is abundant in the body and exists in several forms, including bone marrow, mammary tissue, and mechanical, brown, and white adipose tissues. It is speculated that ASCs arrive in adipose tissue via distribution of circulating fibroblasts derived from the bone marrow that then colonize the respective adipose tissues throughout the body. Transplanted bone marrow-derived fibroblasts similar to the ones already discussed have been shown capable of differentiating into adipocytes upon proper chemical stimulation and in the presence of a lipid-rich diet; however, the exact origin and distribution of ASC populations remains unknown. Regarding the relative abundance of stem cell populations within the body’s various adipose depots, current evidence suggests that richer concentrations of progenitor cells exist in the arm and abdomen relative to samples taken from the thigh or breast. Further studies, along with effective
