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The myofibroblast, multiple origins for major roles in normal and pathological tissue repair.

Micallef L, Vedrenne N, Billet F, Coulomb B, Darby IA, Desmoulière A - Fibrogenesis Tissue Repair (2012)

Bottom Line: Myofibroblasts originate from different precursor cells, the major contribution being from local recruitment of connective tissue fibroblasts.However, local mesenchymal stem cells, bone marrow-derived mesenchymal stem cells and cells derived from an epithelial-mesenchymal transition process, may represent alternative sources of myofibroblasts when local fibroblasts are not able to satisfy the requirement for these cells during repair.These diverse cell types probably contribute to the appearance of myofibroblast subpopulations which show specific biological properties and which are important to understand in order to develop new therapeutic strategies for treatment of fibrotic and scarring diseases.

View Article: PubMed Central - HTML - PubMed

Affiliation: Facultés de Médecine et de Pharmacie, Université de Limoges, EA 6309 "Maintenance Myélinique et Neuropathies Périphériques", FR 3503, Limoges F-87025, France.

ABSTRACT
Myofibroblasts differentiate, invade and repair injured tissues by secreting and organizing the extracellular matrix and by developing contractile forces. When tissues are damaged, tissue homeostasis must be re-established, and repair mechanisms have to rapidly provide harmonious mechanical tissue organization, a process essentially supported by (myo)fibroblasts. Under physiological conditions, the secretory and contractile activities of myofibroblasts are terminated when the repair is complete (scar formation) but the functionality of the tissue is only rarely perfectly restored. At the end of the normal repair process, myofibroblasts disappear by apoptosis but in pathological situations, myofibroblasts likely remain leading to excessive scarring. Myofibroblasts originate from different precursor cells, the major contribution being from local recruitment of connective tissue fibroblasts. However, local mesenchymal stem cells, bone marrow-derived mesenchymal stem cells and cells derived from an epithelial-mesenchymal transition process, may represent alternative sources of myofibroblasts when local fibroblasts are not able to satisfy the requirement for these cells during repair. These diverse cell types probably contribute to the appearance of myofibroblast subpopulations which show specific biological properties and which are important to understand in order to develop new therapeutic strategies for treatment of fibrotic and scarring diseases.

No MeSH data available.


Related in: MedlinePlus

Schematic illustration showing the evolution of the (myo)fibroblast phenotype. The myofibroblastic modulation of fibroblastic cells begins with the appearance of the proto-myofibroblast, whose stress fibers contain only β- and γ-cytoplasmic actins and evolves, but not necessarily always, into the appearance of the differentiated myofibroblast, the most common variant of this cell, with stress fibers containing α-smooth muscle actin. The myofibroblast may disappear by apoptosis; the deactivation leading to a quiescent phenotype has not been clearly demonstrated at least in vivo. TGF-β1: transforming growth factor-β1; ECM: extracellular matrix. Modified from [38].
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Figure 1: Schematic illustration showing the evolution of the (myo)fibroblast phenotype. The myofibroblastic modulation of fibroblastic cells begins with the appearance of the proto-myofibroblast, whose stress fibers contain only β- and γ-cytoplasmic actins and evolves, but not necessarily always, into the appearance of the differentiated myofibroblast, the most common variant of this cell, with stress fibers containing α-smooth muscle actin. The myofibroblast may disappear by apoptosis; the deactivation leading to a quiescent phenotype has not been clearly demonstrated at least in vivo. TGF-β1: transforming growth factor-β1; ECM: extracellular matrix. Modified from [38].

Mentions: Immediately after wounding, the healing process allowing restoration of injured tissue occurs. Wound healing proceeds in three interrelated dynamic phases with overlapping time courses. According to morphological changes in the course of the healing process, these phases are described as an inflammatory phase, a proliferative phase for the development of granulation tissue, and a regeneration phase for maturation, scar formation and re-epithelialisation [3]. The inflammatory phase begins with damage to the capillaries, which triggers the formation of a blood clot consisting of fibrin and fibronectin. This provisional matrix will fill in the lesion and will allow the various recruited cells to migrate into wound. Platelets present in the blood clot release multiple chemokines which participate in the recruitment not only of inflammatory cells (neutrophils and macrophages), but also fibroblasts and endothelial cells. The second stage of wound healing is the proliferative phase. Active angiogenesis which is critical for the wound healing process, allows new capillaries to deliver nutrients including oxygen to the wound, and contributes to the proliferation of fibroblasts. In the granulation tissue, fibroblasts become activated and acquire a smooth muscle cell-like phenotype; they are consequently called myofibroblasts. These myofibroblastic cells synthesize and deposit the extracellular matrix components which will replace the provisional matrix. These cells also exhibit contractile properties, due to the expression of α-smooth muscle actin in microfilament bundles or stress fibers, playing a major role in the contraction and in maturation of the granulation tissue [4] (Figure 1). Presently, it is accepted that the myofibroblastic modulation of fibroblastic cells begins with the appearance of the protomyofibroblast, whose stress fibers contain only β- and γ-cytoplasmic actins. Protomyofibroblasts evolve in most cases into differentiated myofibroblasts, the most common variant of this cell, with stress fibers containing α-smooth muscle actin (for review, see [5]) (Figure 1). Myofibroblasts can, depending on the experimental or clinical situation, express other smooth muscle cell specific contractile proteins, such as smooth muscle-myosin heavy chains or desmin; however, the presence of α-smooth muscle actin represents the most reliable marker of the myofibroblastic phenotype [6]. The third phase of healing, scar formation, involves a progressive remodelling of the granulation tissue. During this remodelling process, proteolytic enzymes, essentially matrix metalloproteinases (MMPs) and their inhibitors (TIMPs for tissue inhibitor of metalloproteinases) play a major role [7]. In the resolution phase of healing, the cell number of vascular cells and myofibroblasts is dramatically reduced by the process of apoptosis [8] (Figure 1). To date, it has not been clearly shown that myofibroblasts can reacquire a quiescent phenotype.


The myofibroblast, multiple origins for major roles in normal and pathological tissue repair.

Micallef L, Vedrenne N, Billet F, Coulomb B, Darby IA, Desmoulière A - Fibrogenesis Tissue Repair (2012)

Schematic illustration showing the evolution of the (myo)fibroblast phenotype. The myofibroblastic modulation of fibroblastic cells begins with the appearance of the proto-myofibroblast, whose stress fibers contain only β- and γ-cytoplasmic actins and evolves, but not necessarily always, into the appearance of the differentiated myofibroblast, the most common variant of this cell, with stress fibers containing α-smooth muscle actin. The myofibroblast may disappear by apoptosis; the deactivation leading to a quiescent phenotype has not been clearly demonstrated at least in vivo. TGF-β1: transforming growth factor-β1; ECM: extracellular matrix. Modified from [38].
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3368789&req=5

Figure 1: Schematic illustration showing the evolution of the (myo)fibroblast phenotype. The myofibroblastic modulation of fibroblastic cells begins with the appearance of the proto-myofibroblast, whose stress fibers contain only β- and γ-cytoplasmic actins and evolves, but not necessarily always, into the appearance of the differentiated myofibroblast, the most common variant of this cell, with stress fibers containing α-smooth muscle actin. The myofibroblast may disappear by apoptosis; the deactivation leading to a quiescent phenotype has not been clearly demonstrated at least in vivo. TGF-β1: transforming growth factor-β1; ECM: extracellular matrix. Modified from [38].
Mentions: Immediately after wounding, the healing process allowing restoration of injured tissue occurs. Wound healing proceeds in three interrelated dynamic phases with overlapping time courses. According to morphological changes in the course of the healing process, these phases are described as an inflammatory phase, a proliferative phase for the development of granulation tissue, and a regeneration phase for maturation, scar formation and re-epithelialisation [3]. The inflammatory phase begins with damage to the capillaries, which triggers the formation of a blood clot consisting of fibrin and fibronectin. This provisional matrix will fill in the lesion and will allow the various recruited cells to migrate into wound. Platelets present in the blood clot release multiple chemokines which participate in the recruitment not only of inflammatory cells (neutrophils and macrophages), but also fibroblasts and endothelial cells. The second stage of wound healing is the proliferative phase. Active angiogenesis which is critical for the wound healing process, allows new capillaries to deliver nutrients including oxygen to the wound, and contributes to the proliferation of fibroblasts. In the granulation tissue, fibroblasts become activated and acquire a smooth muscle cell-like phenotype; they are consequently called myofibroblasts. These myofibroblastic cells synthesize and deposit the extracellular matrix components which will replace the provisional matrix. These cells also exhibit contractile properties, due to the expression of α-smooth muscle actin in microfilament bundles or stress fibers, playing a major role in the contraction and in maturation of the granulation tissue [4] (Figure 1). Presently, it is accepted that the myofibroblastic modulation of fibroblastic cells begins with the appearance of the protomyofibroblast, whose stress fibers contain only β- and γ-cytoplasmic actins. Protomyofibroblasts evolve in most cases into differentiated myofibroblasts, the most common variant of this cell, with stress fibers containing α-smooth muscle actin (for review, see [5]) (Figure 1). Myofibroblasts can, depending on the experimental or clinical situation, express other smooth muscle cell specific contractile proteins, such as smooth muscle-myosin heavy chains or desmin; however, the presence of α-smooth muscle actin represents the most reliable marker of the myofibroblastic phenotype [6]. The third phase of healing, scar formation, involves a progressive remodelling of the granulation tissue. During this remodelling process, proteolytic enzymes, essentially matrix metalloproteinases (MMPs) and their inhibitors (TIMPs for tissue inhibitor of metalloproteinases) play a major role [7]. In the resolution phase of healing, the cell number of vascular cells and myofibroblasts is dramatically reduced by the process of apoptosis [8] (Figure 1). To date, it has not been clearly shown that myofibroblasts can reacquire a quiescent phenotype.

Bottom Line: Myofibroblasts originate from different precursor cells, the major contribution being from local recruitment of connective tissue fibroblasts.However, local mesenchymal stem cells, bone marrow-derived mesenchymal stem cells and cells derived from an epithelial-mesenchymal transition process, may represent alternative sources of myofibroblasts when local fibroblasts are not able to satisfy the requirement for these cells during repair.These diverse cell types probably contribute to the appearance of myofibroblast subpopulations which show specific biological properties and which are important to understand in order to develop new therapeutic strategies for treatment of fibrotic and scarring diseases.

View Article: PubMed Central - HTML - PubMed

Affiliation: Facultés de Médecine et de Pharmacie, Université de Limoges, EA 6309 "Maintenance Myélinique et Neuropathies Périphériques", FR 3503, Limoges F-87025, France.

ABSTRACT
Myofibroblasts differentiate, invade and repair injured tissues by secreting and organizing the extracellular matrix and by developing contractile forces. When tissues are damaged, tissue homeostasis must be re-established, and repair mechanisms have to rapidly provide harmonious mechanical tissue organization, a process essentially supported by (myo)fibroblasts. Under physiological conditions, the secretory and contractile activities of myofibroblasts are terminated when the repair is complete (scar formation) but the functionality of the tissue is only rarely perfectly restored. At the end of the normal repair process, myofibroblasts disappear by apoptosis but in pathological situations, myofibroblasts likely remain leading to excessive scarring. Myofibroblasts originate from different precursor cells, the major contribution being from local recruitment of connective tissue fibroblasts. However, local mesenchymal stem cells, bone marrow-derived mesenchymal stem cells and cells derived from an epithelial-mesenchymal transition process, may represent alternative sources of myofibroblasts when local fibroblasts are not able to satisfy the requirement for these cells during repair. These diverse cell types probably contribute to the appearance of myofibroblast subpopulations which show specific biological properties and which are important to understand in order to develop new therapeutic strategies for treatment of fibrotic and scarring diseases.

No MeSH data available.


Related in: MedlinePlus