FIBROBLASTS: CHARACTERISTICS, FUNCTIONS, HISTOLOGY, CULTURE - BIOLOGY - 2025

The fibroblasts are a heterogeneous group of cells, also called fibroblast cells. These cell subpopulations include "classical fibroblasts" and other specialized fibroblast types such as myofibroblasts, lipofibroblasts, the contractile interstitial cell (CIC), and pericytes.

Classic fibroblasts are the main cells that are part of the connective tissue structure of the body, but they are also responsible for maintaining this tissue.

Fibroblasts

Their morphology will depend on the site where they are found and they are mainly responsible for synthesizing fibers and a collagen precursor, as well as maintaining the extracellular matrix of the tissues.

Basically they are the cells that form the supporting structure of the organs in living beings (animals and humans). By synthesizing fibers, collagen, mucopolysaccharides (glycosaminoglycan) and glycoproteins (fibronectin), they play a fundamental role in the repair of tissues, being protagonists in the healing processes.

During wound healing, fibroblasts migrate to the injury site where they proliferate to restore collagen.

General characteristics

The structure of fibroblasts varies according to the state in which the cell is, in addition, these cells will be different according to their function and the place where they are located.

Fibroblasts are characterized by presenting two states; one active and one inactive. Therefore, in the active condition they are called fibroblasts and in the inactive condition fibrocytes.

Fibroblasts and fibrocytes are also known as young cell and mature cell respectively. However, they are generally called fibroblasts interchangeably, to refer to either state.

Fibroblasts

The active cell (fibroblast), as its name indicates, has high secretory activity.

These are large cells (50 to 100 microns long and 30 wide), flat (3 microns thick), and spindle-shaped (spindle-shaped, wide in the center and thin toward the ends).

In addition, they present a variety of irregular cytoplasmic processes, which can be short and wide, or elongated, thin and highly branched. These branches help you maintain a relationship with other fibroblasts through simple physical connections or contacts.

They are also related to the rest of the cells that surround it in the connective tissue, including: muscle cells, neurons, endothelial cells, leukocytes, among others.

Communication occurs through direct physical friction, using the extracellular matrix as an intermediary or through the secretion of substances.

On the other hand, the nucleus of fibroblasts is clear, flat and oval. It also has one or two prominent nucleoli that disappear in the fibrocyte.

These cells possess a group of organelles characteristic of high synthetic and secretory activity: abundant rough endoplasmic reticulum, a well-developed Golgi complex, secretory vesicles rich in tropocollagen, ribosomes and mitochondria.

Another characteristic that stands out in these cells is the presence of a complex cytoskeleton. It is made up of a system of microtubules and microfilaments, formed mainly by the expression of F, β and γ actins, plus α actinin.

These elements are grouped in the cell periphery contiguous to myosin.

This structure is typical of a multifunctional cell. It also provides the ability to move at a speed of 1 µm / min, accumulating at the ends of wounds to repair tissue and form scars.

Fibrocytes

Fibrocytes are smaller, spindle-shaped cells with sparser cytoplasm, few organelles and fewer cytoplasmic processes. Its nucleus is dark, elongated and smaller.

Although the fibrocyte is in a resting (non-secreting) form and does not usually divide frequently, it can go into mitosis and re-synthesize fibers if connective tissue injury occurs.

Features

In the past it was thought that the function of fibroblasts was very simple, since it was only classified as a support tissue for other cell types. But today it is known that fibroblasts are very dynamic cells and their functions are complex.

The specific function of each fibroblast, as well as its morphology, will depend on its location in the body, the lineage to which it belongs, and the perceived stimuli.

Fibroblasts, even being in the same place, can perform different functions, according to the stimulus they receive from the cells that surround them.

Maintenance and remodeling of connective tissue

Its main function is related to the maintenance of connective tissue, which is made up of fibers (collagen, reticular and elastic) and the extracellular matrix.

Fibroblasts maintain the extracellular matrix of tissues, synthesizing certain compounds that compose it, in the state of precursors and also some fibers. But they not only synthesize them, they are also capable of engulfing some of these components in tissue remodeling processes.

Among the compounds that make up the extracellular matrix are: fibrous proteins and the amorphous ground substance, made up mainly of hyaluronic acid and interstitial plasma.

The process of synthesis and remodeling of the extracellular matrix carried out by fibroblasts is carried out through the production of a wide variety of enzymes belonging to the family of metalloproteinases.

These enzymes are interstitial collagenase, gelatinase A, proteoglycanases, glycosaminoglycanases, and tissue inhibitors of metalloproteinase.

These enzymes participate in the synthesis of various substances such as type I and III collagenases, elastic fibers, fibronectin, proteoglycans, glycoproteins, proteins, and proteases.

Interaction with other cells and participation in the immune response

Another function that stands out in fibroblasts is their ability to interact with local cells and intervene in the early stages of the immune response, as they are capable of initiating the inflammation process in the presence of invading pathogens.

In this sense, they provoke the synthesis of chemokines through the presentation of receptors on their surface, as well as other chemical mediators such as interleukins, neuropeptides and various growth factors.

They can sometimes participate as antigen-presenting cells to T cells, although this function is not as common.

Other functions

On the other hand, fibroblasts provide the ability for connective tissue to adhere to surrounding tissues.

They also present contractility and motility used in the structural organization of connective tissue, primarily during embryogenesis.

In addition, fibroblasts will perform their functions depending on the site where they are found and the characteristics of each cell lineage. For example, gingival fibroblasts cement the soft connective tissue that surrounds the alveolar bone (gingiva).

Meanwhile, the fibroblasts of the periodontal ligament surround the root portion of the tooth, producing and maintaining the implantation of the connective tissue that provides a stable anchoring of the same inside the alveolus.

Likewise, the fibroblasts in the skin are very diverse, one of their functions being to keep the skin smooth and silky due to the synthesis of collagen, elastin or proteoglycans.

With age the function of these cells decreases and this causes typical signs of aging such as wrinkles to appear. They are also attributed the induction of hair follicles, sweat glands, among others.

Histology

Fibroblasts originate from primitive and pluripotent mesenchymal cells.

In some emergency occasions, the organism, through a process called epithelial-mesenchymal transition (EMT), is capable of forming fibroblasts from epithelial cells.

The opposite process of transformation of fibroblasts to epithelial cells is also possible through the mesenchymal-epithelial transition process (MET).

Therefore, it is possible that fibroblasts can differentiate into specialized epithelial cells such as adipocytes, chondrocytes, among others.

This process is useful in tissue repair, but it also occurs in malignant processes such as tumor growth.

Culture

The dynamism of this cell has made it an attractive target for research and since it has been relatively easy to manipulate at the in vitro level, it has been studied through cell cultures in the laboratory.

These investigations have revealed important data, for example:

In cultures of fibroblasts from embryonic tissue, it has been observed that they are capable of making up to 50 divisions before they age and degenerate.

This characteristic has made them ideal cells to study the human karyotype.

However, the capacity for division is considerably decreased in fibroblasts from adult tissue, in which approximately 20 divisions are observed.

Likewise, the cosmetic industry currently uses the cultivation of fibroblasts to obtain molecules that can be introduced into the skin, to combat the typical signs of aging.

In this sense, they have proposed a regenerative treatment, currently used in the US The treatment consists of filling in wrinkles by injecting autologous (own) fibroblasts directly.

To do this, they take a small piece of tissue extracted from the back of the patient's ears. As they are their own fibroblasts, they do not generate rejection and in this way the autogeneration of collagen, elastin, among other substances, is reactivated.

Fibroblast-related diseases

The malfunction of these cells is related to some pathologies. The most important ones are mentioned below:

Venous ulcers

Venous ulcers are low in collagen and fibronectin.

Specifically, it has been seen that the capacity for collagen production by fibroblasts in the lesion is decreased, while fibronectin production is normal.

It is believed that the low production of collagen is due to the presence of a low oxygen level (hypoxia) in the tissues, and the scarcity of fibronectin to a greater degradation of the same in the ulcer.

Scleroderma

It is a fairly rare and chronic autoimmune disease that consists of the accumulation of diffuse fibrotic tissue.

It also causes degenerative changes and abnormalities manifested in the skin, the walls of small arteries, joints and internal organs.

The pathological fibrosis that occurs in this disease is characterized by uncontrolled activation of fibroblasts, which unleashes excessive and constant accumulation and remodeling of the extracellular matrix.

Rheumatoid arthritis

It is a chronic autoimmune disease that affects the joints, characterized by inflammation of the joints, which causes deformation and a lot of pain.

Synovial fibroblasts, the main cellular component of the joint synovium, play an important role in the development of rheumatoid arthritis. In this pathology, synovial fibroblasts increase in number (hyperplasia).

They also show an atypical phenotype, related to the activation of certain intracellular signaling pathways, which provoke cell growth and the expression of multiple pro-inflammatory substances.

All of this contributes to the chemotaxis, accumulation and activation of inflammatory cells, angiogenesis and the deterioration of bone and cartilage.

References

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3. Acosta A. The fibroblast: its origin, structure, functions and heterogeneity within the periodontium. Universitas Odontológica, 2006; 25 (57): 26-33
4. Sriram G, Bigliardi PL, Bigliardi-Qi M. Fibroblast heterogeneity and its implications for engineering organotypic skin models in vitro. European journal of cell biology. 2015; 94: 483-512.
5. Izquierdo E, Pablos J. Synovial fibroblasts. Seminars of the Spanish Foundation of Rheumatology. 2013; 14 (4): 95-142