MSC：Mesenchymal Stem Cell or Multipotent Stromal Cell
Mesenchymal stem cells, or MSCs, are multipotent stromal cells that can differentiate into a variety of cell types, including：Osteoblasts (bone cells), Chondrocytes (cartilage cells), 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 as discussed below：
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.
Because the cells, called MSCs by many labs today, can encompass multipotent cells derived from other non-marrow tissues, such as umbilical cord blood, adipose tissue, adult muscle, corneal stroma or the dental pulp of deciduous baby teeth, yet do not have the capacity to reconstitute an entire organ, the term Multipotent Stromal Cell has been proposed as a better replacement.
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 Wharton’s 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, nervous tissues, including a minimum of 29 different unique end organs. Because of extreme ease in collection at 8–10 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 very rich source of stem cells. As many as 1 in 100 cells collected from and genetic amniocentesis has been shown to be a Pluripotent mesenchymal stem cell.
Adipose tissue is one of the richest sources of MSCs. When compared to bone marrow, there is more than 500 times more stem cells in 1 gram of fat when compared to 1 gram of aspirated bone marrow. Adipose stem cells are currently actively being researched in clinical trials for treatment in 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.
In 1924, Russian-born morphologist Alexander A. Maximow used extensive histological findings to identify a singular type of precursor cell within mesenchyme that develops into different types of blood cells.
Scientists Ernest A. McCulloch and James E. Till first revealed the clonal nature of marrow cells in the 1960s. An ex vivo assay for examining the clonogenic potential of multipotent marrow cells was later reported in the 1970s by Friedenstein and colleagues. In this assay system, stromal cells were referred to as colony-forming unit-fibroblasts (CFU-f).
Subsequent experimentation revealed the plasticity of marrow cells and how their fate could be determined by environmental cues. Culturing marrow stromal cells in the presence of osteogenic stimuli such as ascorbic acid, inorganic phosphate, and dexamethasone could promote their differentiation into Osteoblasts. In contrast, the addition of Transforming growth factor-beta (TGF-b) could induce Chondrogenic markers.
The mesenchymal stem cells can be activated and mobilized if needed. However, the efficiency is very low. For instance, damage to muscles heals very slowly. However, if there were a method of activating the mesenchymal stem cells, then such wounds would heal much faster.
Many of the early clinical successes using intravenous transplantation have come in systemic diseases like graft versus host disease and sepsis. However, it is becoming more accepted that diseases involving peripheral tissues, such as inflammatory bowel disease, may be better treated with methods that increase the local concentration of cells. Direct injection or placement of cells into a site in need of repair may be the preferred method of treatment, as vascular delivery suffers from a "Pulmonary first pass effect" where intravenous injected cells are Sequestered in the lungs. Clinical case reports in orthopedic applications have been published, though the number of patients treated is small and these methods still lack rigorous study demonstrating effectiveness. Wakitani has published a small case series of nine defects in five knees involving surgical transplantation of mesenchymal stem cells with coverage of the treated chondral defects.
留言列表
