Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contact Us Login 
An Official Publication of the Indian Association of Oral and Maxillofacial Pathologists

  Table of Contents    
Year : 2011  |  Volume : 15  |  Issue : 2  |  Page : 247-250

Heterogenecity of fibroblasts

Department of Oral Pathology, Vishnu Dental College and Hospital, Bhimavaram, India

Date of Web Publication5-Sep-2011

Correspondence Address:
Manyam Ravikanth
Department of Oral Pathology, Vishnu Dental College, Bhimavaram
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-029X.84516

Rights and Permissions



Fibroblasts are a major stromal cell type present in human connective tissue maintaining the structural integrity in health. Depending on the situation, location and various conditions, fibroblasts exhibit considerable variation in morphology, size and shape that suggest the existence of discrete cellular subsets. The purpose of this short communication is to provide information regarding the heterogenecity of fibroblasts and its variability in physiological and pathological conditions.

Keywords: Fibroblasts, fibrocytes, giant cell fibroblasts, myofibroblasts

How to cite this article:
Ravikanth M, Soujanya P, Manjunath K, Saraswathi T R, Ramachandran C R. Heterogenecity of fibroblasts. J Oral Maxillofac Pathol 2011;15:247-50

How to cite this URL:
Ravikanth M, Soujanya P, Manjunath K, Saraswathi T R, Ramachandran C R. Heterogenecity of fibroblasts. J Oral Maxillofac Pathol [serial online] 2011 [cited 2022 Dec 3];15:247-50. Available from: https://www.jomfp.in/text.asp?2011/15/2/247/84516

   Introduction Top

Mesenchymal cells are precursors for a varied group of connective tissue cells including endothelial cells, smooth muscle cells, pericytes, chondroblasts, adipocytes, osteoblasts, odontoblasts, and fibroblasts. Fibroblasts are a heterogeneous population of cells found in numerous tissues. The interrelationships between cell lineages and differentiation potential contribute to wide range of synthetic products, rates of product synthesis, reaction to regulatory molecules, cellular turnover rates and morphological features leads to fibroblast diversity. The tissue distribution and relative proportion of fibroblast subpopulations have a considerable impact on the regulation of connective tissue function in health and disease. [1]

   Fibroblasts Top

The fibroblasts are predominant stromal cell type seen in soft connective tissues. They appear as plump spindle shaped or stellate shaped cells (active fibroblasts) with centrally placed oval or round nucleus [Figure 1]. These cells and their extracellular matrix products i.e. fibers and amorphous ground substance play pivotal roles in maintaining the structural integrity of connective tissues in health, healing processes, and in pathological alterations. In addition to well-described structural and functional similarities (e.g. collagen and fibronectin synthesis, vimentin intermediate filaments [Figure 2], β-actin), fibroblasts exhibit considerable variation of cytoskeletal proteins (e.g. α-smooth muscle actin expression), surface markers and size, that suggests the existence of discrete cellular subsets. Fibroblast variants can be seen both within a localized site (e.g. gingiva) and also between sites from various locations. The central hypotheses proposed that fibroblasts are phenotypically stable but exhibit heterogeneous subpopulations, which regulate tissue form and function. Fibroblasts exhibit change in morphology and appear as elongated cells with thin flat/wavy nuclei (inactive fibroblasts) in the areas of dense collagen fibre formation [Figure 3]. Fibroblasts can also undertake other functions (e.g., as immune accessory cells), which extend their utility as "architects and caretakers of connective tissues". [1] Fibrosarcoma [Figure 4], a malignant mesenchymal neoplasm of fibroblasts or fibrohistiocytic lesions derived from a peculiar type of fibroblastic mesenchymal cell that show histiocytic areas and many other neoplasms can develop from fibroblasts.
Figure 1: Active fibroblasts, 20×

Click here to view
Figure 2: Vimentin positive, 20×

Click here to view
Figure 3: Inactive fibroblasts, 20×

Click here to view
Figure 4: Fibrosarcoma, 20×

Click here to view

   Fibrocytes Top

Fibroblasts found in the wound are considered essential for the healing process. The concept that wound fibroblasts originating from peripheral blood cells goes back almost 100 years. Since then, numerous studies have reported the differentiation of peripheral mononuclear cells into fibroblast-like cells. In 1994, a distinct population of blood-borne fibroblast-like cells that rapidly enter sites of tissue injury was described and were termed fibrocytes. [2] These cells comprise 0.1 - 0.5% of non-erythrocytic cells in peripheral blood and show an adherent, spindle-shaped morphology. Fibrocytes express collagen (Col) I, Col III, and fibronectin, as well as the leukocyte common Ag (CD45RO), the pan-myeloid Ag (CD13), and the hemopoietic stem cell Ag (CD34). In addition, fibrocytes express MHC class II and costimulatory molecules (CD80 and CD86). Morphology, growth properties and cell surface markers of fibrocytes appear to be distinct from monocytes/macrophages, dendritic cells, and other antigen presenting cell types. [3]

Based on their presence in wounds and their secretion of proinflammatory cytokines, chemokines, and extracellular matrix proteins, fibrocytes have been postulated to play a role in connective tissue formation in wound healing.

   Myofibroblasts Top

Myofibroblasts (MF) are modified fibroblasts with smooth muscle like features characterized by the presence of contractile apparatus. Myofibroblasts disclose several typical histologic traits characterized by large, spindle shaped stellate cells with long cytoplasmic extensions, amphophillic cytoplasm and indented nucleus with conspicuous nucleoli. These are extremely heterogenous and multifunctional cell population exhibiting a different phenotype and first discovered by electron microscopy in experimental granulation tissue. MF plays a key role in extracellular matrix synthesis, reorganization and tissue contraction during both physiologic process and pathologic process like wound healing and tumorigenesis. [4]

Ultrastructurally these cells disclose irregular, stellate cellular outlines with numerous long cytoplasmic connections connected by intermediate or adherens junctions and are connected to the extracellular matrix by cell-to-stroma attachment sites through fibronexus. They contain bundles of cytoplasmic filaments arranged parallel to the long axis of the cell, a well developed rough endoplasmic reticulum, golgi and indented nucleus with prominent nucleoli. [5]

Myofibroblasts discloses five cytoskeletal immuno phenotypes: Phenotype V, represented by cells expressing only vimentin; phenotype VA represented by cells expressing vimentin and alpha smooth muscle actin (α-SMA); phenotype VAD represented by cells expressing vimentin, α-SMA and desmin; phenotype VD represented by cells expressing vimentin and desmin; phenotype VAM represented by cells expressing vimentin, α-SMA and myosin. Most of the MF expresses alpha smooth muscle actin (α-SMA), an actin isoform found in vascular smooth muscle cells and regulated by TGF-β and is considered as main immunohistochemical marker of myofibroblastic differentiation. [6]

   Myofibroblasts in Oral Tissues Top

In the oral cavity these MF were reported in the human palatal mucosa and granulation tissue during wound healing. The process of wound healing is highly orchestrated sequence of events in which myofibroblasts appear to be key cells. Prostaglandins derived from myofibroblast are key factors in promoting healing by restitution and reconstitution of the epithelium. Another important event in wound healing is the contraction of the wound which is due to the myofibroblasts because of the presence of alpha smooth muscle actin filaments in the cytoplasm of these cells. The extra cellular matrix complex is a mixture of collagens, glycoproteins and proteoglycans that form a scaffold for tissue formation. Type I, III, IV and VIII collagens, fibronectin, tenascin are secreted by the myofibroblasts and tissue remodelling following injury which is mediated mainly by the matrix metalloproteinases, which are also secreted by the myofibroblasts. [7]

Myofibroblasts have been reported in many locally aggressive odontogenic lesions like odontogenic keratocyst [Figure 5] and solid ameloblastomas. In oral submucous fibrosis there was significant increase of myofibroblasts when compared to that of the normal control and could be used as markers for evaluating the severity of oral submucous fibrosis. The abundant myofibroblasts at the invasion front of oral squamous cell carcinomas [Figure 6] contribute in growth of the tumor cells by secreting angiogenic molecules, growth factors and invasion by secretion of matrix metalloproteinases and suppression of host immune response. [8]
Figure 5: α SMA positive myofibroblasts in odontogenic keratocyst, 10×

Click here to view
Figure 6: α SMA positive myofibroblasts in squamous cell carcinoma, 20×

Click here to view

   Giant Cell Fibroblasts Top

Giant cell fibroma (GF) is characterized by the presence of many large stellate mono or multinucleate giant cells in a fibrous tissue containing abundant collagen and the degree of fibrosis varies from area to area within the fibrous tissue [Figure 7]. In Giant Cell Fibroma, the giant cells are located beneath the epithelium. The cytoplasmic borders of these cells are usually distinct with some fading at the apex of angular extension. The cytoplasm is basophilic, granular, containing some vacuoles [Figure 8]. Some of these cells, especially those located beneath the epithelium may contain small brown granules with the staining characteristics of melanin. An artefactual space separating the giant cells from the collagen fibers is sometimes present. The overlying epithelium is hyperplastic with thin elongated retepegs and the inflammatory infiltrate is usually minimal. Common irritation hyperplasias like fibrous hyperplasia, fibroepithelial polyp, fibroma show similar histologic features but the presence of numerous stellate giant cells differentiates giant cell fibroma from other lesions.
Figure 7: Giant cell fibroblasts in subepithelial region, 20×

Click here to view
Figure 8: Giant cell fibroblasts, 40×

Click here to view

Ultra structurally, giant fibroblasts appear as stellate cells with a large hyperchromatic nucleus, while the cytoplasm is well demarcated and frequently the cells show dendritic-like processes; multinucleated giant cells in giant cell fibroma are unusual fibroblasts. [9]

Immunohistochemical studies on giant fibroblasts showed positivity only for Vimentin and negative reactivity for cytokeratin, neurofilament, HHF, CD68, HLA DR, tryptase, leukocyte common antigen, S100 protein. [10]

   References Top

1.Lekic PC, Pender N, McCulloch CA. Is fibroblast heterogeneity relevant to the health, diseases and treatments of periodontal tissues? Crit Rev Oral Biol Med 1997;8:253-68.  Back to cited text no. 1
2.Bucala R, Spiegel LA, Chesney J, Hogan M, Cerami A. Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair. Mol Med 1994;1:71-81.  Back to cited text no. 2
3.Abe R, Donnelly SC, Peng T, Bucala R, Metz CN. Peripheral blood fibrocytes: Differentiation pathway and migration to wound sites. J Immunol 2001;166:7556-62.  Back to cited text no. 3
4.Majno G, Gabbiani G, Hirschel BJ, Ryan GB, Statkov PR. Contraction of granulation tissue in vitro: similarity to smooth muscle. Science 1971;173:548-50.  Back to cited text no. 4
5.Gabbiani G, Chaponnier C, Huttner I. Cytoplasmic filaments and gap junctions in epithelial cells and myofibroblasts during wound healing. J Cell Biol 1978;76:561-8.  Back to cited text no. 5
6.Schurch W, Seemayer TA, Gabbiani G. Myofibroblast. In: Sternberg SS, editor. Histology for Pathologists. Philadelphia: Lippincott-Raven Publishers; 1997. p. 129-65.  Back to cited text no. 6
7.Powell DW. Myofibroblasts: Paracrine cells important in health and disease. Trans Am Clin Climatol Assoc 2000;111:271-93.  Back to cited text no. 7
8.Vered M, Shohat I, Buchner A, Dayan D. Myofibroblasts in the stroma of odontogenic cysts and tumors can contribute to variation in the biologic behavior of lesions. Oral Oncol 2005;41:1028-33.  Back to cited text no. 8
9.Takeda Y, Kaneko R, Suzuki A, Niitsu J. Giant cell fibroma of the oral mucosa. Report of a case with ultrastructural study. Acta Pathol Jpn 1986;36:1571-6.  Back to cited text no. 9
10.Reibel J. Oral fibrous hyperplasias containing stellate and multinucleated cells. Scand J Dent Res 1982;90:217-26.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]

This article has been cited by
1 ‘Youthful’ phenotype of c-Kit+ cardiac fibroblasts
Fareheh Firouzi, Oscar Echeagaray, Carolina Esquer, Natalie A. Gude, Mark A. Sussman
Cellular and Molecular Life Sciences. 2022; 79(8)
[Pubmed] | [DOI]
2 Role of Cultured Skin Fibroblasts in Regenerative Dermatology
Mohammad Ali Nilforoushzadeh, Ebrahim Khodaverdi Darian, Hamideh Afzali, Mohammad Amir Amirkhani, Mohammadreza Razzaghi, Reza Naser, Amir Behtash Amiri, Alimohammad Alimohammadi, Nahid Nikkhah, Sona Zare
Aesthetic Plastic Surgery. 2022;
[Pubmed] | [DOI]
3 Influence of poly(styrene sodium sulfonate) grafted silicone breast implant’s surface on the biological response and its mechanical properties
M. Lam, R. Vayron, R. Delille, V. Migonney, C. Falentin-Daudré
Materials Today Communications. 2022; : 103318
[Pubmed] | [DOI]
4 Wound healing, fibroblast heterogeneity, and fibrosis
Heather E. Talbott, Shamik Mascharak, Michelle Griffin, Derrick C. Wan, Michael T. Longaker
Cell Stem Cell. 2022; 29(8): 1161
[Pubmed] | [DOI]
5 Antifibrosis Efficacy of Apo-9-Fucoxanthinone-Contained Sargassum horneri Ethanol Extract on Nasal Polyp: An In Vitro and Ex Vivo Organ Culture Assay
Mi-Jin Yim, Jeong Min Lee, Seok-Chun Ko, Hyun-Soo Kim, Ji-Yul Kim, Seong Kook Park, Dae-Sung Lee, Il-Whan Choi
Current Issues in Molecular Biology. 2022; 44(11): 5815
[Pubmed] | [DOI]
6 Antioxidant Properties of Plant-Derived Phenolic Compounds and Their Effect on Skin Fibroblast Cells
Anna Merecz-Sadowska, Przemyslaw Sitarek, Ewa Kucharska, Tomasz Kowalczyk, Karolina Zajdel, Tomasz Ceglinski, Radoslaw Zajdel
Antioxidants. 2021; 10(5): 726
[Pubmed] | [DOI]
7 Fibroblasts: Heterogeneous Cells With Potential in Regenerative Therapy for Scarless Wound Healing
Ming-Li Zou, Ying-Ying Teng, Jun-Jie Wu, Si-Yu Liu, Xiao-Yu Tang, Yuan Jia, Zhong-Hua Chen, Kai-Wen Zhang, Zi-Li Sun, Xia Li, Jun-Xing Ye, Rui-Sheng Xu, Feng-Lai Yuan
Frontiers in Cell and Developmental Biology. 2021; 9
[Pubmed] | [DOI]
8 Landscape of extracellular vesicles in the tumour microenvironment: Interactions with stromal cells and with non-cell components, and impacts on metabolic reprogramming, horizontal transfer of neoplastic traits, and the emergence of therapeutic resistance
Daniel Xin Zhang, Luyen Tien Vu, Nur Nadiah Ismail, Minh T.N. Le, Andrew Grimson
Seminars in Cancer Biology. 2021; 74: 24
[Pubmed] | [DOI]
9 Stromal cell interplay in prostate development, physiology, and pathological conditions
Bruno D. A. Sanches, Juliana S. Maldarine, Patricia S. L. Vilamaior, Sergio L. Felisbino, Hernandes F. Carvalho, Sebastião R. Taboga
The Prostate. 2021; 81(13): 926
[Pubmed] | [DOI]
10 Label-Free Isolation and Single Cell Biophysical Phenotyping Analysis of Primary Cardiomyocytes Using Inertial Microfluidics
Hossein Tavassoli, Prunella Rorimpandey, Young Chan Kang, Michael Carnell, Chris Brownlee, John E Pimanda, Peggy P.Y. Chan, Vashe Chandrakanthan
Small. 2021; 17(8): 2006176
[Pubmed] | [DOI]
11 Biomarkers and heterogeneous fibroblast phenotype associated with incisional hernia
Finosh G. Thankam, Nicholas K. Larsen, Ann Varghese, Thao-Nguyen Bui, Matthew Reilly, Robert J. Fitzgibbons, Devendra K. Agrawal
Molecular and Cellular Biochemistry. 2021; 476(9): 3353
[Pubmed] | [DOI]
12 Al2O3 nanoparticle polymorphs: effects of Zn2+ doping on the structural, optical and cytotoxic properties
Jéssica de Lara Andrade, Angélica Gonçalves de Oliveira, Leonardo Sobreira Rodrigues, Mychelle Vianna Pereira Companhoni, Celso Vataru Nakamura, Sandro Marcio Lima, Luis Humberto da Cunha Andrade, Luiz Fernando Cótica, Ana Adelina Winkler Hechenleitner, Edgardo Alfonso Gómez Pineda, Daniela Martins Fernandes de Oliveira
Bulletin of Materials Science. 2021; 44(1)
[Pubmed] | [DOI]
13 New Gene Markers Involved in Molecular Processes of Tissue Repair, Response to Wounding and Regeneration Are Differently Expressed in Fibroblasts from Porcine Oral Mucosa during Long-Term Primary Culture
Artur Bryja, Patrycja Sujka-Kordowska, Aneta Konwerska, Sylwia Ciesiólka, Maria Wieczorkiewicz, Dorota Bukowska, Pawel Antosik, Rut Bryl, Mariusz T. Skowronski, Jedrzej M. Jaskowski, Paul Mozdziak, Ana Angelova Volponi, Jamil A. Shibli, Bartosz Kempisty, Marta Dyszkiewicz-Konwinska
Animals. 2020; 10(11): 1938
[Pubmed] | [DOI]
14 Transcriptomic and Morphological Analysis of Cells Derived from Porcine Buccal Mucosa—Studies on an In Vitro Model
Artur Bryja, Grzegorz Latosinski, Maurycy Jankowski, Ana Angelova Volponi, Paul Mozdziak, Jamil A. Shibli, Rut Bryl, Julia Spaczynska, Hanna Piotrowska-Kempisty, Krzysztof Krawiec, Bartosz Kempisty, Marta Dyszkiewicz-Konwinska
Animals. 2020; 11(1): 15
[Pubmed] | [DOI]
15 Understanding the impact of fibroblast heterogeneity on skin fibrosis
Michelle F. Griffin, Heather E. desJardins-Park, Shamik Mascharak, Mimi R. Borrelli, Michael T. Longaker
Disease Models & Mechanisms. 2020; 13(6)
[Pubmed] | [DOI]
16 Pengaruh Pemberian Salep Kolagen Hidrolisat Ikan Sebagai Penyembuhan Luka Bakar Derajat IIB Berdasarkan Ekspresi Fibroblast Growth Factor 2 (FGF-2) dan Fibroblas pada Tikus Putih (Rattus norvegicus)
Lutfiana Pratiwi
Media Kedokteran Hewan. 2020; 31(2): 52
[Pubmed] | [DOI]
17 Silk Sericin-Functionalized Bacterial Cellulose as a Potential Wound-Healing Biomaterial
Lallepak Lamboni, Ying Li, Jianfeng Liu, Guang Yang
Biomacromolecules. 2016; 17(9): 3076
[Pubmed] | [DOI]


Print this article  Email this article


    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
  Related articles
    Article in PDF (4,067 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  

    Myofibroblasts i...
    Giant Cell Fibro...
    Article Figures

 Article Access Statistics
    PDF Downloaded943    
    Comments [Add]    
    Cited by others 17    

Recommend this journal

© Journal of Oral and Maxillofacial Pathology | Published by Wolters Kluwer - Medknow
Online since 15th Aug, 2007