The Role of Stem Cells in Dupuytren’s Disease: A Review

Tan, Kirin; Withers, Aaron H. J.; Tan, Swee T.; Itinteang, Tinte

doi:10.1097/gox.0000000000001777

Cited by 9 publications

(8 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These aberrant fibroblasts and myofibroblasts may originate from mesenchymal stem cells (MSCs) through a process of epithelial-to-mesenchymal transition or endothelial-to-mesenchymal transition (EndoMT), or from bone marrow mesenchymal precursors, as proposed for Dupuytren’s disease. 27,28…”

Section: Fibroblasts and Myofibroblastsmentioning

confidence: 99%

Stem Cells in Keloid Lesions: A Review

Lim

Itinteang

Davis

et al. 2019

Plastic and Reconstructive Surgery - Global Open

Self Cite

View full text Add to dashboard Cite

Summary: Keloid disorder (KD) is a fibroproliferative condition caused by dysregulated wound healing following wounding of the skin. The pathogenesis of KD has not been fully elucidated and current treatment is unsatisfactory. There is increasing evidence of the role of stem cells in KD. This review discusses the role of embryonic stem (ESC)-like cells and mesenchymal stem cells in the pathogenesis of KD. It is proposed that dysfunction of the ESC-like population localized to the endothelium of the microvessels and perivascular cells within the keloid-associated lymphoid tissues may give rise to the aberrant fibroblasts and myofibroblasts via a mesenchymal stem cell intermediate in keloid lesions, by undergoing an endothelial-to-mesenchymal transition. We also discuss the role of the renin-angiotensin system (RAS), the immune system, and the inflammatory response, on stem cell proliferation and differentiation. The understanding of the precise roles of these stem cells and interplay of the associated regulatory pathways could lead to the development of targeted therapy for this enigmatic and challenging condition. The demonstration of the expression of components of the RAS and cathepsins B, D, and G that constitute bypass loops of the RAS, by the ESC-like population, suggests that the primitive population may be a therapeutic target by modulation of the RAS, using existing medications.

show abstract

Section: Fibroblasts and Myofibroblastsmentioning

confidence: 99%

Stem Cells in Keloid Lesions: A Review

Lim

Itinteang

Davis

et al. 2019

Plastic and Reconstructive Surgery - Global Open

Self Cite

View full text Add to dashboard Cite

show abstract

“…Aberrant keloid fibroblasts and myofibroblasts may be derived from an ESC-like population in keloid-associated lymphoid tissues (KALTs) (25) through a mesenchymal stem cell intermediate, by the process of endo-MT and epithelial-tomesenchymal transition (EMT) (Figure 2), or from bone marrow mesenchymal precursors as proposed for Dupuytren's disease (29,37,38).…”

Section: Fibroblasts and Myofibroblasts In Keloid Disordermentioning

confidence: 99%

The Role of the Renin-Angiotensin System and Vitamin D in Keloid Disorder—A Review

et al. 2019

Self Cite

View full text Add to dashboard Cite

Keloid disorder (KD) is a fibroproliferative condition characterized by excessive dermal collagen deposition in response to wounding and/or inflammation of the skin. Despite intensive research, treatment for KD remains empirical and unsatisfactory. Activation of the renin-angiotensin system (RAS) leads to fibrosis in various organs through its direct effect and the resultant hypertension, and activation of the immune system. The observation of an increased incidence of KD in dark-skinned individuals who are predisposed to vitamin D deficiency (VDD) and hypertension, and the association of KD with hypertension and VDD, all of which are associated with an elevated activity of the RAS, provides clues to the pathogenesis of KD. There is increasing evidence implicating embryonic-like stem (ESC) cells that express ESC markers within keloid-associated lymphoid tissues (KALTs) in keloid lesions. These primitive cells express components of the RAS, cathepsins B, D, and G that constitute bypass loops of the RAS, and vitamin D receptor (VDR). This suggests that the RAS directly, and through signaling pathways that converge on the RAS, including VDR-mediated mechanisms and the immune system, may play a critical role in regulating the primitive population within the KALTs. This review discusses the role of the RAS, its relationship with hypertension, vitamin D, VDR, VDD, and the immune system that provide a microenvironmental niche in regulating the ESC-like cells within the KALTs. These ESC-like cells may be a novel therapeutic target for the treatment of this enigmatic and challenging condition, by modulating the RAS using inhibitors of the RAS and its bypass loops and convergent signaling pathways.

show abstract

“…There is accumulating evidence for the critical role of cells that possess embryonic stem cell (ESC) characteristics and the expression of components of the renin-angiotensin system (RAS), in different types of vascular anomalies (VAs) ( 1 ), cancer ( 2 – 6 ), and fibroproliferative conditions ( 7 – 9 ).…”

Section: Introductionmentioning

confidence: 99%

Insights Into Vascular Anomalies, Cancer, and Fibroproliferative Conditions: The Role of Stem Cells and the Renin-Angiotensin System

Kilmister

Tan

2022

Front. Surg.

Self Cite

View full text Add to dashboard Cite

Cells exhibiting embryonic stem cell (ESC) characteristics have been demonstrated in vascular anomalies (VAs), cancer, and fibroproliferative conditions, which are commonly managed by plastic surgeons and remain largely unsolved. The efficacy of the mTOR inhibitor sirolimus, and targeted therapies that block the Ras/BRAF/MEK/ERK1/2 and PI3KCA/AKT/mTOR pathways in many types of cancer and VAs, further supports the critical role of ESC-like cells in the pathogenesis of these conditions. ESC-like cells in VAs, cancer, and fibroproliferative conditions express components of the renin-angiotensin system (RAS) – a homeostatic endocrine signaling cascade that regulates cells with ESC characteristics. ESC-like cells are influenced by the Ras/BRAF/MEK/ERK1/2 and PI3KCA/AKT/mTOR pathways, which directly regulate cellular proliferation and stemness, and interact with the RAS at multiple points. Gain-of-function mutations affecting these pathways have been identified in many types of cancer and VAs, that have been treated with targeted therapies with some success. In cancer, the RAS promotes tumor progression, treatment resistance, recurrence, and metastasis. The RAS modulates cellular invasion, migration, proliferation, and angiogenesis. It also indirectly regulates ESC-like cells via its direct influence on the tissue microenvironment and by its interaction with the immune system. In vitro studies show that RAS inhibition suppresses the hallmarks of cancer in different experimental models. Numerous epidemiological studies show a reduced incidence of cancer and improved survival outcomes in patients taking RAS inhibitors, although some studies have shown no such effect. The discovery of ESC-like cells that express RAS components in infantile hemangioma (IH) underscores the paradigm shift in the understanding of its programmed biologic behavior and accelerated involution induced by β-blockers and angiotensin-converting enzyme inhibitors. The findings of SOX18 inhibition by R-propranolol suggests the possibility of targeting ESC-like cells in IH without β-adrenergic blockade, and its associated side effects. This article provides an overview of the current knowledge of ESC-like cells and the RAS in VAs, cancer, and fibroproliferative conditions. It also highlights new lines of research and potential novel therapeutic approaches for these unsolved problems in plastic surgery, by targeting the ESC-like cells through manipulation of the RAS, its bypass loops and converging signaling pathways using existing low-cost, commonly available, and safe oral medications.

show abstract

The Role of Stem Cells in Dupuytren’s Disease: A Review

Cited by 9 publications

References 59 publications

Stem Cells in Keloid Lesions: A Review

Stem Cells in Keloid Lesions: A Review

The Role of the Renin-Angiotensin System and Vitamin D in Keloid Disorder—A Review

Insights Into Vascular Anomalies, Cancer, and Fibroproliferative Conditions: The Role of Stem Cells and the Renin-Angiotensin System

Contact Info

Product

Resources

About