Mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells or medicinal signaling cells, are multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts (bone-making cells), chondrocytes (cartilage cells), myocytes (muscle cells) and adipocytes (fat cells which give rise to marrow adipose tissue). The primary function of MSCs is to respond to injury and infection by secreting and recruiting a range of biological factors, as well as modulating inflammatory processes to facilitate tissue repair and regeneration. Extensive research interest has led to more than 80,000 peer-reviewed papers on MSCs.
Structure
Definition Mesenchymal stem cells (MSCs), a term first used (in 1991) by Arnold Caplan at Case Western Reserve University, are characterized morphologically by a small cell body with long, thin cell processes. The International Society for Cellular Therapy has identified a few criteria to define mesenchymal stem cell (MSC):
MSC must be plastic-adherent when maintained in standard culture conditions. MSC must express CD105, CD73 and CD90, and lack expression of CD45, CD34, CD14 or CD11b, CD79alpha or CD19 and HLA-DR surface molecules. MSC must differentiate to osteoblasts, adipocytes and chondroblasts in vitro. While the terms mesenchymal stem cell (MSC) and marrow stromal cell have been used interchangeably for many years, neither term is sufficiently descriptive:
Mesenchyme is embryonic connective tissue that is derived from the mesoderm and that differentiates into hematopoietic and connective tissue, whereas MSCs do not differentiate into hematopoietic cells. Stromal cells are connective tissue cells that form the supportive structure in which the functional cells of the tissue reside. While this is an accurate description for one function of MSCs, the term fails to convey the relatively recently discovered roles of MSCs in the repair of tissue. The term encompasses multipotent cells derived from other non-marrow tissues, such as placenta, umbilical cord blood, adipose tissue, adult muscle, corneal stroma, or the dental pulp of deciduous (baby) teeth. The cells do not have the capacity to reconstitute an entire organ. Evidence shows that MSCs originate from progenitor perivascular cells called pericytes that reside on vessels.
Morphology
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. These distinctive morphological features of mesenchymal stem cells can be visualized label-free using live cell imaging.
Classification Reviews have classified an MSC as having fibroblast-like structure, characterized by cell-surface markers and a potential to differentiate into bone, fat, or cartilage.
Location in the body MSCs are found throughout the human body.
Bone marrow Bone marrow was the original source of MSCs, and is still the most frequently utilized source. These bone marrow stem cells do not contribute to the formation of blood cells, and so do not express the hematopoietic stem cell marker CD34. They are sometimes referred to as bone marrow stromal stem cells.
Cord cells The youngest and most primitive MSCs may be obtained from umbilical cord tissue, namely Wharton's jelly and the umbilical cord blood. However, MSCs are found in much higher concentration in the Wharton's jelly compared to cord blood, which is a rich source of hematopoietic stem cells. The umbilical cord is available after a birth. It is normally discarded, and poses no risk for collection. These MSCs may prove to be a useful source of MSCs for clinical applications, due to their primitive properties and fast growth rate.
Adipose tissue Adipose-tissue-derived MSCs (AdMSCs), in addition to being easier and safer to isolate than bone-marrow-derived MSCs, can be obtained in larger quantities.
Molar cells The developing tooth bud of the mandibular third molar is a rich source of MSCs. While they are described as multipotent, it is possible that they are pluripotent. They eventually form enamel, dentin, blood vessels, dental pulp, and nervous tissues. These stem cells are capable of differentiating into chondrocytes, cardiomyocytes, melanocytes, and hepatocyte‐like cells in vitro.
Amniotic fluid Stem cells are present in amniotic fluid. As many as 1 in 100 cells collected during amniocentesis are pluripotent mesenchymal stem cells.
Function
Differentiation capacity MSCs have a great capacity for self-renewal while maintaining their multipotency. Recent work suggests that β-catenin, via regulation of EZH2, is a central molecule in maintaining the "stemness" of MSCs. The standard test to confirm multipotency is differentiation of the cells into osteoblasts, adipocytes and chondrocytes as well as myocytes. Doubt remains about whether the MSC-derived neurons are functional. The degree to which the culture will differentiate varies among individuals and how differentiation is induced, e.g., chemical vs. mechanical; 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.
… excerpt ends here. Continue reading the full article.
