active after cleavage. Levels of TNFα positively correlate with obesity and insulin resistance. Induction of insulin resistance can be achieved in vitro and in vivo via chronic TNFα exposure.4 Interleukin-6 (IL-6) is similar to TNFα in that it is a cytokine produced by adipose tissue that also is associated with obesity and insulin resistance, and circulating levels have been shown to decrease with weight loss. It also serves as a predictor of type 2 diabetes as well as cardiovascular disease.
Adipose tissue excess (obesity). Associations of obesity are referred to as metabolic syndrome and are characterized by insulin resistance, hyperglycemia, dyslipidemia, hypertension, and prothrombotic and proinflammatory states.
Adipose tissue deficiency (lipodystrophy). A deficiency of adipose is also associated with characteristics of metabolic syndrome.
Krishna S. Vyas
Christopher Areephanthu
University of Kentucky College of Medicine
See Also: Adipose: Cells Types Composing the Tissue; 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.
Further Readings
Cannon, B. and Jan Nedergaard. “Brown Adipose Tissue: Function and Physiological Significance.” Physiological Reviews, v.84/1 (January 1, 2004).
Kershaw, E. E. and J. S. Flier. “Adipose Tissue as an Endocrine Organ.” Journal of Clinical Endocrinology and Metabolism, v.89 (2004).
Trayhurn, P. and J. H. Beattie. “Physiological Role of Adipose Tissue: White Adipose Tissue as an Endocrine and Secretory Organ.” Proceedings of the Nutrition Society, v.14/3 (2001).
Adult Stem Cells: Overview
Adult Stem Cells: Overview
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Adult Stem Cells: Overview
About 65 years ago, a team of researchers discovered that red bone marrow was composed of two types of stem cells: hematopoietic stem cells (HSCs) described as mesoderm-derived blood cells, and stromal stem cells. Cells of the mesoderm form one of the three primary germ cell layers of an embryo in its early stages of development, and give rise to other blood cells. Stromal stem cells, on the other hand, constitute the so-called skeletal or mesenchymal layer. The role of these stem cells, which only make up a fraction of all stromal cells, is to generate cartilage, bone, and fat cells able to support the formation of fibrous connective tissue and blood.
Despite these findings, most scientists remained convinced for a long time that the adult human brain was unable to produce new nerve cells. In the 1990s, however, researchers reached the conclusion that the matured brain did contain stem cells, capable of generating star-shaped glial cells called astrocytes, located in the spinal cord and the brain, and oligodendrocytes, which provide insulation and support to axons, long nerve fiber extensions present in the central nervous system (CNS) of some vertebrates.
While hematopoietic stem cells only produce white blood cells, red blood cells, and platelets, adult stem cells, in contrast, mutate into different kinds of cells susceptible of dividing and reproducing indefinitely.
What are adult stem cells (ASCs) all about? And more specifically, how do they differ from pluripotent stem cells, or rapidly dividing progenitor transit amplifying cells (TACs)? Why are they so important to science and regenerative medicine? What are the challenges, if any, associated to their use?
By definition, “adult stem cells are undifferentiated cells, found throughout the body after embryonic development, that multiply by cell division to replenish dying cells and regenerate damaged tissue.” They are also known as somatic stem cells, found in young and adult animals, and humans.
Many different types of stem cells arise at different locations in the human body, from adult or tissue-specific stem cells, to embryonic stem cells that exist only briefly in the early stages of tissue development. In addition to these, researchers have recently created induced pluripotent stem cells, or iPSCs. These are undifferentiated cells engineered from specialized cells, with characteristics almost identical to those of embryonic stem cells.
Adult or tissue-specific stem cells are deemed to be multipotent, that is, capable of giving rise to a few mature cell types.
Adult stem cells are present in many different tissues and organs, including brain, blood, vessels, skin, skeletal muscle, heart, testis, ovarian epithelium, and bone marrow. In the bone marrow, several millions of new blood cells arise every day from blood-forming stem cells. Scientists have not been able to determine whether every mature organ includes stem cells. Tissue-specific stem cells are rare and often difficult to grow in culture and isolate. Of those, the blood-forming and hematopoietic stem cells residing in the bone marrow are the most studied.
Induced pluripotent stem cells (iPSCs) are cells engineered to become pluripotent, that is, capable of forming multiple types of cell types. Although human iPSCs open up an exciting window into stem cell research, this technology is still in its infancy, and many related crucial questions remain unanswered.
A promising avenue of stem cell research resides in the replacement of affected or damaged cells with healthy ones, an approach defined as regenerative medicine. This field has prompted scientists to investigate the use of fetal, embryonic, and adult stem cells derived from various specialized cell types—muscle, nerve, blood, and skin cells—to assess their use as potential treatment for various conditions.
However, it is important to keep in mind that in some instances, the immune system itself may be the source of so-called autoimmune diseases that damage vital cells, such as the ones producing insulin in type 1 diabetes patients.
The end goal of stem cell–based regenerative medicine—the restoration of the function of damaged or lost tissues and organs—can be achieved through different means such as the injection of stem cells engineered in the laboratory, or the administration of drugs susceptible of coaxing existing stem cells into carrying out a more efficient repair.
However, in spite of the encouraging prospects presented by potential stem cell therapies, there are challenges in the use of stem cells for regenerative purposes. In adult individuals, tissue-specific stem cells are rare and tend to be difficult to isolate. Additionally, while adult stem cells hold the promise of self-regeneration in animals and humans, the fact that they only exist in minute quantities creates some hurdles in the sense that they must be identified in sufficient numbers in order to be usable for therapy. All this makes it harder to conduct effective clinical studies. Researchers from various laboratories are currently attempting to find ways to grow and collect large enough quantities of adult stem cells susceptible to generate specific cell types.
Blood-forming stem cells make up only a tiny fraction of the bone marrow. Although, they can be isolated in the laboratory, these cells cannot be conserved for a long time. Some cells, such as skin stem cells, offer better expansion capabilities in the laboratory and are used for specific treatments like burns. Other types of stem cells, such as bone marrow cells, can be infused in the blood stream. Mesenchymal muscle and neural stem cells, on the other hand,
