Mesenchymal stem cells, or MSCs, are multipotent stromal cells that can differentiate into a variety of cell types,[1] including: osteoblasts (bone cells),[2]chondrocytes (cartilage cells),[3]myocytes (muscle cells)[4] and adipocytes (fat cells). This phenomenon has been documented in specific cells and tissues in living animals and their counterparts growing in tissue culture.

While the terms mesenchymal stem cell and marrow stromal cell have been used interchangeably, neither term is sufficiently descriptive:

The youngest, most primitive MSCs can be obtained from the umbilical cord tissue, namely Wharton's jelly and the umbilical cord blood. However the MSCs are found in much higher concentration in the Whartons jelly compared to the umbilical cord blood, which is a rich source of hematopoietic stem cells. The umbilical cord is easily obtained after the birth of the newborn, is normally thrown away, and poses no risk for collection. The umbilical cord MSCs have more primitive properties than other adult MSCs obtained later in life, which might make them a useful source of MSCs for clinical applications.

An extremely rich source for mesenchymal stem cells is the developing tooth bud of the mandibular third molar. While considered multipotent, they may prove to be pluripotent. The stem cells eventually form enamel, dentin, blood vessels, dental pulp, and nervous tissues, including a minimum of 29 different unique end organs. Because of extreme ease in collection at 810 years of age before calcification, and minimal to no morbidity, they will probably constitute a major source for personal banking, research, and multiple therapies. These stem cells have been shown capable of producing hepatocytes.

Additionally, amniotic fluid has been shown to be a rich source of stem cells. As many as 1 in 100 cells collected during amniocentesis has been shown to be a pluripotent mesenchymal stem cell.[9]

Adipose tissue is one of the richest sources of MSCs. There are more than 500 times more stem cells in 1 gram of fat than in 1 gram of aspirated bone marrow. Adipose stem cells are actively being researched in clinical trials for treatment of a variety of diseases.

The presence of MSCs in peripheral blood has been controversial. However, a few groups have successfully isolated MSCs from human peripheral blood and been able to expand them in culture.[10] Australian company Cynata also claims the ability to mass-produce MSCs from induced pluripotent stem cells obtained from blood cells using the method of K. Hu et al.[11][12]

Mesenchymal stem cells are characterized morphologically by a small cell body with a few cell processes that are long and thin. The cell body contains a large, round nucleus with a prominent nucleolus, which is surrounded by finely dispersed chromatin particles, giving the nucleus a clear appearance. The remainder of the cell body contains a small amount of Golgi apparatus, rough endoplasmic reticulum, mitochondria, and polyribosomes. The cells, which are long and thin, are widely dispersed and the adjacent extracellular matrix is populated by a few reticular fibrils but is devoid of the other types of collagen fibrils.[13][14]

The International Society for Cellular Therapy (ISCT) has proposed a set of standards to define MSCs. A cell can be classified as an MSC if it shows plastic adherent properties under normal culture conditions and has a fibroblast-like morphology. In fact, some argue that MSCs and fibroblasts are functionally identical.[15] Furthermore, MSCs can undergo osteogenic, adipogenic and chondrogenic differentiation ex-vivo. The cultured MSCs also express on their surface CD73, CD90 and CD105, while lacking the expression of CD11b, CD14, CD19, CD34, CD45, CD79a and HLA-DR surface markers.[16]

MSCs have a great capacity for self-renewal while maintaining their multipotency. Beyond that, there is little that can be definitively said. The standard test to confirm multipotency is differentiation of the cells into osteoblasts, adipocytes, and chondrocytes as well as myocytes and neurons. MSCs have been seen to even differentiate into neuron-like cells,[17][18] but there is lingering doubt whether the MSC-derived neurons are functional.[19] The degree to which the culture will differentiate varies among individuals and how differentiation is induced, e.g., chemical vs. mechanical;[20] and it is not clear whether this variation is due to a different amount of "true" progenitor cells in the culture or variable differentiation capacities of individuals' progenitors. The capacity of cells to proliferate and differentiate is known to decrease with the age of the donor, as well as the time in culture. Likewise, whether this is due to a decrease in the number of MSCs or a change to the existing MSCs is not known.[citation needed]

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