fibrocyte, mesenchymal stem cell, fibroblast

[문형철]

고등학교때 물리와 지구과학을 선택과목으로 공부했다. 

이후 생물학, 분자생물학 등의 기초개념 부족으로 힘든 과정을 거쳐오고 있다. 

또 다시 생물학, 분자생물학의 기초, 기초개념부터 해야하는 불편함이 있다. 

모든 과학, 의학, 뇌과학, 문학, 철학을 통합해야하는 시대에 살면서 탐구의 끝이 없음을 온몸으로 느낀다.

panic bird...

fibrocyte = inactive mesenchymal stem cell과 동의어

fibroblast는 콜라겐과 섬유기질을 합성하는 활성화된 결합조직 세포

myo-fibroblast는 액틴의 형태를 포함한 섬유아세포.

A fibrocyte is an inactive mesenchymal cell, that is, a cell showing minimal cytoplasm, limited amounts of rough endoplasmic reticulum and lacks biochemical evidence of protein synthesis.

The term fibrocyte contrasts with the term fibroblast. Fibroblasts are activated connective tissue cells characterized by synthesis of proteins of the fibrous matrix, particularly the collagens. 

When tissue is injured, the predominant mesenchymal cells, the fibroblast, have been believed to be derived from the fibrocyte or possibly from smooth muscle cells lining vessels and glands. Commonly, fibroblasts express smooth muscle actin, a form of actin first found in smooth muscle cells and not found in resting fibrocytes. Fibroblasts expressing this form of actin are usually called "myo-fibroblasts."

Recently, the term "fibrocyte" has also been applied to a blood borne cell able to leave the blood, enter tissue and become a fibroblast. As part of the more general topic of stem cell biology, a number of studies have suggested that the blood contains marrow derived cells that can differentiate into fibroblasts. These cells have been reported to express the hematopoietic cell surface markers CD34+, CD45+, as well as collagen. These cells can migrate to wound sites, suggesting a role in wound healing. There are several studies suggesting that fibrocytes mediate wound healing and fibrotic tissue repair.

mesenchymal stem cell

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] and adipocytes(fat cells). This phenomenon has been documented in specific cells and tissues in living animals and their counterparts growing in tissue culture.

Characteristics[edit]

Morphology[edit]

Human bone marrow derived Mesenchymal stem cell showing fibroblast like morphology seen under phase contrast microscope (carl zeiss axiovert 40 CFL) at 63 x magnification

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, andpolyribosomes. 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.^[14][15]

Detection[edit]

The 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.^[16] 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-DRsurface markers. ^[17]

Differentiation capacity[edit]

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,^[18] [19] but there is lingering doubt whether the MSC-derived neurons are functional.^[20] The degree to which the culture will differentiate varies among individuals and how differentiation is induced, e.g., chemical vs. mechanical;^[21] 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]}

Immunomodulatory effects[edit]

Numerous studies have demonstrated that human MSCs avoid allorecognition, interfere with dendritic cell and T-cell function, and generate a local immunosuppressive microenvironment by secreting cytokines.^[22] It has also been shown that the immunomodulatory function of human MSC is enhanced when the cells are exposed to an inflammatory environment characterised by the presence of elevated local interferon-gamma levels.^[23] Other studies contradict some of these findings, reflecting both the highly heterogeneous nature of MSC isolates and the considerable differences between isolates generated by the many different methods under development.^[24]

섬유아세포 

A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen,^[1] the structural framework (stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells of connective tissue in animals.

Background information[edit]

Fibroblasts and fibrocytes are two states of the same cells, the former being the activated state, the latter the less active state, concerned with maintenance and tissue metabolism. Currently, there is a tendency to call both forms fibroblasts. The suffix "blast" is used in cellular biology to denote astem cell or a cell in an activated state of metabolism.

Fibroblasts are morphologically heterogeneous with diverse appearances depending on their location and activity. Though morphologically inconspicuous,ectopically transplanted fibroblasts can often retain positional memory of the location and tissue context where they had previously resided, at least over a few generations. This remarkable behavior may lead to discomfort^{[clarification needed]} in the rare event that they stagnate there excessively.

Embryologic origin[edit]

The main function of fibroblasts is to maintain the structural integrity of connective tissues by continuously secreting precursors of the extracellular matrix. Fibroblasts secrete the precursors of all the components of the extracellular matrix, primarily the ground substance and a variety of fibers. The composition of the extracellular matrix determines the physical properties of connective tissues.

Like other cells of connective tissue, fibroblasts are derived from primitive mesenchyme. Thus they express the intermediate filament protein vimentin, a feature used as a marker to distinguish their mesodermal origin. However, this test is not specific as epithelial cells cultured in vitro on adherent substratum may also express vimentin after some time.

In certain situations epithelial cells can give rise to fibroblasts, a process called epithelial-mesenchymal transition (EMT).

Conversely, fibroblasts in some situations may give rise to epithelia by undergoing a mesenchymal to epithelial transition (MET) and organizing into a condensed, polarized, laterally connected true epithelial sheet. This process is seen in many developmental situations (e.g. nephron and notocorddevelopment), as well as in wound healing and tumorigenesis.

Structure and function[edit]

Microfilaments, Mitochondria, and Nuclei in Fibroblast Cells

Fibroblasts have a branched cytoplasm surrounding an elliptical, speckled nucleus having two or more nucleoli. Active fibroblasts can be recognized by their abundant rough endoplasmic reticulum. Inactive fibroblasts, which are also called fibrocytes^{[citation needed]}, are smaller and spindle shaped. They have a reduced rough endoplasmic reticulum. Although disjointed and scattered when they have to cover a large space, fibroblasts, when crowded, often locally align in parallel clusters.

Fibroblasts make collagens, glycosaminoglycans, reticular and elastic fibers, glycoproteins found in theextracellular matrix, and cytokine TSLP. Growing individuals' fibroblasts are dividing and synthesizing ground substance. Tissue damage stimulates fibrocytes and induces the mitosis of fibroblasts.

Unlike the epithelial cells lining the body structures, fibroblasts do not form flat monolayers and are not restricted by a polarizing attachment to a basal lamina on one side, although they may contribute to basal lamina components in some situations (e.g. subepithelial myofibroblasts in intestine may secrete the α-2 chain carrying component of the laminin which is absent only in regions of follicle-associated epithelia which lack the myofibroblast lining). Fibroblasts can also migrate slowly over substratum as individual cells, again in contrast to epithelial cells. While epithelial cells form the lining of body structures, it is fibroblasts and related connective tissues which sculpt the "bulk" of an organism.

The life span of a fibroblast, as measured in chick embryos, is 57 ± 3 days.^[2]

Secondary actions[edit]

Mouse embryonic fibroblasts (MEFs) are often used as "feeder cells" in human embryonic stem cell research. However, many researchers are gradually phasing out MEFs in favor of culture media with precisely defined ingredients of exclusively human derivation^{[citation needed]}. Further, the difficulty of exclusively using human derivation for media supplements is most often solved by the use of "defined media" where the supplements are synthetic and achieve the primary goal of eliminating the chance of contamination from derivative sources.