Papers by Natacha Agabalyan
iScience, 2020
The adult hair follicle (HF) undergoes successive regeneration driven by resident epithelial stem... more The adult hair follicle (HF) undergoes successive regeneration driven by resident epithelial stem cells and neighboring mesenchyme. Recent work described the existence of HF dermal stem cells (hfDSCs), but the genetic regulation of hfDSCs and their daughter cell lineages in HF regeneration remains unknown. Here we prospectively isolate functionally distinct mesenchymal compartment in the HF (dermal cup [DC; includes hfDSCs] and dermal papilla) and define the transcriptional programs involved in hfDSC function and acquisition of divergent mesenchymal fates. From this, we demonstrate cross-compartment mesenchymal signaling within the HF niche, whereby DP-derived R-spondins act to stimulate proliferation of both hfDSCs and epithelial progenitors during HF regeneration. Our findings describe unique transcriptional programs that underlie the functional heterogeneity among specialized fibroblasts within the adult HF and identify a novel regulator of mesenchymal progenitor function during tissue regeneration.
British Journal of Oral and Maxillofacial Surgery, 2019
Stem Cell Reports, 2019
Following full-thickness skin injuries, epithelialization of the wound is essential. The standard... more Following full-thickness skin injuries, epithelialization of the wound is essential. The standard of care to achieve this wound ''closure'' in patients is autologous split-thickness skin grafting (STSG). However, patients living with STSGs report significant chronic impairments leading to functional deficiencies such as itch, altered sensation, fragility, hypertrophic scarring, and contractures. These features are attributable to the absence of functional dermis combined with the formation of disorganized fibrotic extracellular matrix. Recent work has demonstrated the existence of dermal progenitor cells (DPCs) residing within hair follicles that function to continuously regenerate mesenchymal tissue. The present work examines whether cultured DPCs could regenerate dermis within an STSG and improve overall graft function. Adult human DPCs were transplanted into a full-thickness skin wound in immune-compromised mice and closed with a human STSG. At 3 months, human DPCs (hDPCs) had successfully integrated into the xenograft and differentiated into various regionally specified phenotypes, improving both viscoelastic properties of the graft and mitigating pruritus.
Experimental Dermatology, 2017
Understanding the cellular interactions and molecular signals underlying hair follicle (HF) regen... more Understanding the cellular interactions and molecular signals underlying hair follicle (HF) regeneration may have significant implications for restorative therapies for skin disease that diminish hair growth, whilst also serving to provide fundamental insight into the mechanisms underlying adult tissue regeneration. One of the major, yet underappreciated, players in this process is the underlying HF mesenchyme. Here, we provide an overview of a mesenchymal progenitor pool referred to as hair follicle dermal stem cells (hfDSCs), discuss their potential functions within the skin and their relationship to skin-derived precursors (SKPs), and consider unanswered questions about the function of these specialized fibroblasts. We contend that dermal stem cells provide an important reservoir of renewable dermal progenitors that may enable development of novel restorative therapies following hair loss, skin injury or disease.
Scientific Reports, 2017
Cell-based therapies have recently been the focus of much research to enhance skin wound healing.... more Cell-based therapies have recently been the focus of much research to enhance skin wound healing. An important challenge will be to develop vehicles for cell delivery that promote survival and uniform distribution of cells across the wound bed. These systems should be stiff enough to facilitate handling, whilst soft enough to limit damage to newly synthesized wound tissue and minimize patient discomfort. Herein, we developed several novel modifiable nanofibre scaffolds comprised of Poly (ε-caprolactone) (PCL) and gelatin (GE). We asked whether they could be used as a functional receptacle for adult human Skin-derived Precursor Cells (hSKPs) and how naked scaffolds impact endogenous skin wound healing. PCL and GE were electrospun in a single facile solvent to create composite scaffolds and displayed unique morphological and mechanical properties. After seeding with adult hSKPs, deposition of extracellular matrix proteins and sulphated glycosaminoglycans was found to be enhanced in composite grafts. Moreover, composite scaffolds exhibited significantly higher cell proliferation, greater cell spreading and integration within the nanofiber mats. Transplantation of acellular scaffolds into wounds revealed scaffolds exhibited improvement in dermal-epidermal thickness, axonal density and collagen deposition. These results demonstrate that PCL-based nanofiber scaffolds show promise as a cell delivery system for wound healing. Besides providing a physical barrier that prevents pathologic infection, skin also performs a range of vital functions that maintain hydration, thermoregulation and body metabolism. Severe skin injury, such as burns and chronic non-healing wounds, result in lifelong functional impairment and, due to their need for chronic medical care, represent a substantial burden on healthcare. It is estimated that there are 6.5 million patients with chronic wounds in the United States alone, costing US$25 billion annually 1. In particular, full thickness burns, in which both the epidermal and dermal compartments are damaged, are unable to repair to their full capacity 2. Mammalian wound healing has evolved in favor of rapid closure, resulting in dysfunctional fibrotic scars. One promising approach to promote regeneration whilst minimizing scar is to engineer the local environment to promote coordinated cellular infiltration, organized deposition of extracellular matrix (ECM) and to provide instructive cues to promote regeneration of neodermis and appendage formation when combined with competent dermal cells. An ideal cell scaffold should resemble the native extracellular matrix and be capable of supporting cell adhesion, proliferation and maturation. Electrospun mats have the potential to mimic the dermal ECM and
Burns : journal of the International Society for Burn Injuries, Aug 25, 2017
Stem Cells Translational Medicine, 2016
Endogenous dermal stem cells (DSCs) reside in the adult hair follicle mesenchyme and can be isola... more Endogenous dermal stem cells (DSCs) reside in the adult hair follicle mesenchyme and can be isolated and grown in vitro as self-renewing colonies called skin-derived precursors (SKPs). Following transplantation into skin, SKPs can generate new dermis and reconstitute the dermal papilla and connective tissue sheath, suggesting they could have important therapeutic value for the treatment of skin disease (alopecia) or injury. Controlled cell culture processes must be developed to efficiently and safely generate sufficient stem cell numbers for clinical use. Compared with static culture, stirred-suspension bioreactors generated fivefold greater expansion of viable SKPs. SKPs from each condition were able to repopulate the dermal stem cell niche within established hair follicles. Both conditions were also capable of inducing de novo hair follicle formation and exhibited bipotency, reconstituting the dermal papilla and connective tissue sheath, although the efficiency was significantly r...
Journal of burn care & research : official publication of the American Burn Association, Jan 20, 2016
Marjolin's ulcer (MU) is an aggressive malignancy arising within chronic wounds. A major caus... more Marjolin's ulcer (MU) is an aggressive malignancy arising within chronic wounds. A major cause is unhealed burn injuries. This results in well-differentiated squamous cell carcinoma (SCC). This study aimed to elucidate transcriptional changes leading to malignancy by investigating differentially expressed genes in squamous cells present in a SCC compared with MU. MU tumor cells were isolated from histologically confirmed biopsy of SCC within an unhealed burn scar. Epithelial cells (ECs) adjacent to the tumor were co-isolated and a SCC cell line was commercially purchased. mRNA from all three samples was isolated and its expression was quantified using RNASeq. Threshold of log2fold change >2-fold in either direction was considered "differentially expressed." Gene expression analysis revealed distinct differences in gene expression in MU cells compared with EC (665 genes), EC and SCC (1673 genes). Enrichment analysis confirmed that pathways most affected included 1) e...
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society, Mar 7, 2016
The gold standard treatment for full thickness injuries of the skin is autologous split-thickness... more The gold standard treatment for full thickness injuries of the skin is autologous split-thickness skin grafting. This involves harvesting the epidermis and superficial dermis from healthy skin and transplanting it onto the prepared wound bed. The donor site regenerates spontaneously, but the appendages and cellular components from the dermal layer are excluded from the graft. As a result, the new tissue is inferior; the healed graft site is dry/itchy, has decreased elasticity, increased fragility and altered sensory function. Because this dermal layer is composed of collagen and other extracellular matrix proteins, our aim was to characterize the changes in the dermal collagen after split thickness grafting that could contribute to a deficit in functionality. This will serve as a baseline for future studies designed to improve skin function using pharmacological or cell-based therapies for skin repair. We used a xenograft model whereby human split-thickness grafts were implanted int...
Sox2, 2016
Abstract The skin provides the body with a protective enclosure capable of repelling pathogens an... more Abstract The skin provides the body with a protective enclosure capable of repelling pathogens and other environmental insults. It can be divided into two developmentally distinct layers: the outermost epithelium called the epidermis and the inner mesenchyme called the dermis. Maintenance of this dynamic organ requires local stem/progenitor cells to provide a continuous and coordinated turnover of cells. Not surprisingly, several stem cell populations have been identified in the basal epidermis and the hair follicle, which are responsible for maintaining the skin. Sox2 is a crucial cell fate determinant in embryonic stem cells and in various tissue-resident stem cells and more specifically in maintaining adult stem cells in several epithelial tissues. Similarly in skin, epidermal Sox2 expression is found in basal epidermal keratinocytes as well as in nerve terminal cells and mechanosensory cells called Merkel cells. In the dermis, Sox2 is exclusively expressed in specialized mesenchymal cells that comprise the hair follicle dermal papilla during morphogenesis and throughout adulthood. Here we summarize our current understanding of Sox2 during development and maturation of skin, hair follicle regeneration, and cancer, and after cutaneous injury.
Journal of tissue engineering and regenerative medicine, Jan 8, 2017
Peripheral nerve injury affects 2.8% of trauma patients with severe cases often resulting in long... more Peripheral nerve injury affects 2.8% of trauma patients with severe cases often resulting in long-lived permanent disability, despite nerve repair surgery. Autologous Schwann cell (SC) therapy currently provides an exciting avenue for improved outcomes for these patients, particularly with the possibility to derive SCs from easily-accessible adult skin. However, due to current challenges regarding the efficient expansion of these cells, further optimization is required before they can be seriously considered for clinical application. Here, a microcarrier-based bioreactor system is proposed as a means to scale-up large numbers of adult skin-derived SCs for transplantation into the injured nerve. Bioprocessing parameters that allow for the expansion of adult rodent SCs have been identified, whilst maintaining similar rates of proliferation (as compared to static-grown SCs), expression of SC markers, and, importantly, their capacity to myelinate axons following transplant into the inju...
Understanding the cellular interactions and molecular signals underlying hair follicle (HF) regen... more Understanding the cellular interactions and molecular signals underlying hair follicle (HF) regeneration may have significant implications for restorative therapies for skin disease that diminish hair growth, whilst also serving to provide fundamental insight into the mechanisms underlying adult tissue regeneration. One of the major, yet under appreciated, players in this process is the underlying HF mesenchyme. Here, we provide an overview of a mesenchymal progenitor pool referred to as hair follicle dermal stem cells (hfDSCs), discuss their potential functions within the skin and their relationship to skin-derived precursors (SKPs), and consider unanswered questions about the function of these specialized fibroblasts. We contend that dermal stem cells provide an important reservoir of renewable dermal progenitors that may enable development of novel restorative therapies following hair loss, skin injury or disease.
Endogenous dermal stem cells (DSCs) reside in the adult hair follicle mesenchyme and can be isola... more Endogenous dermal stem cells (DSCs) reside in the adult hair follicle mesenchyme and can be isolated and grown in vitro as self-renewing colonies called skin-derived precursors (SKPs). Following trans-plantation into skin, SKPs can generate new dermis and reconstitute the dermal papilla and connective tissue sheath, suggesting they could have important therapeutic value for the treatment of skin disease (alopecia) or injury. Controlled cell culture processes must be developed to efficiently and safely generate sufficient stem cell numbers for clinical use. Compared with static culture, stirred-suspension bioreactors generated fivefold greater expansion of viable SKPs. SKPs from each condition were able to repopulate the dermal stem cell niche within established hair follicles. Both conditions were also capable of inducing de novo hair follicle formation and exhibited bipotency, reconstituting the dermal papilla and connective tissue sheath, although the efficiency was significantly reduced in bioreactor-expanded SKPs compared with static conditions. We conclude that automated bioreactor processing could be used to efficiently generate large numbers of autologous DSCs while maintaining their inherent regenerative function. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:1–10 SIGNIFICANCE Recent work has demonstrated the existence of dermal stem cells (DSCs) that reside within adult hair follicles and might serve as a renewable source of inductive dermal cells to regenerate dermis or rejuvenate dermal papilla to restore follicle growth. In order to realize this clinical potential, it is essential that in vitro bioprocesses are developed to rapidly and safely expand DSCs. The present study showed that computer-controlled stirred suspension bioreactors can be used to efficiently and safely generate large numbers of DSCs while maintaining their phenotype and at least some of their inherent inductive function. This builds on a foundation of research supporting automated bioprocessing as an effective approach for culturing stem cells. The bioprocess described has important implications for ex vivo expansion of inductive dermal stem/progenitor cells that could be used for composite skin engineering strategies, drug screens related to hair growth, and the regeneration of dermis within severe skin wounds.
The gold standard treatment for full thickness injuries of the skin is autologous split-thickness... more The gold standard treatment for full thickness injuries of the skin is autologous split-thickness skin grafting. This involves harvesting the epidermis and superficial dermis from healthy skin and transplanting it onto the prepared wound bed. The donor site regenerates spontaneously, but the appendages and cellular components from the dermal layer are excluded from the graft. As a result, the new tissue is inferior; the healed graft site is dry/itchy, has decreased elasticity, increased fragility, and altered sensory function. Because this dermal layer is composed of collagen and other extracellular matrix proteins, the aim was to characterize the changes in the dermal collagen after split thickness grafting that could contribute to a deficit in functionality. This will serve as a baseline for future studies designed to improve skin function using pharmacological or cell-based therapies for skin repair. A xenograft model whereby human split-thickness grafts were implanted into full-thickness defects on immunocompromised (athymic Nu/Nu) mice was used. The grafts were harvested 4 and 8 weeks later. The collagen microstructure was assessed with second harmonic generation with dual-photon microscopy and light polarization analysis. Collagen fiber stiffness and engagement stretch were estimated by fitting the results of biaxial mechanical tensile tests to a histo-mechanical constitutive model. The stiffness of the collagen fibril–proteoglycan complex increased from 682 6 226 kPa/sr to 1016 6 324 kPa/sr between 4 and 8 weeks postgrafting. At the microstructural level there were significant decreases in both thickness of collagen fibers (3.60 6 0.34 lm vs. 2.10 6 0.27 lm) and waviness ratio (2.04 6 0.17 vs. 1.43 6 0.08) of the collagen fibers postgrafting.
Marjolin’s ulcer (MU) is an aggressive malignancy arising within chronic wounds. A major
cause is... more Marjolin’s ulcer (MU) is an aggressive malignancy arising within chronic wounds. A major
cause is unhealed burn injuries. This results in well-differentiated squamous cell carcinoma
(SCC). This study aimed to elucidate transcriptional changes leading to malignancy by
investigating differentially expressed genes in squamous cells present in a SCC compared
with MU. MU tumor cells were isolated from histologically confirmed biopsy of SCC
within an unhealed burn scar. Epithelial cells (ECs) adjacent to the tumor were co-isolated
and a SCC cell line was commercially purchased. mRNA from all three samples was isolated
and its expression was quantified using RNASeq. Threshold of log2fold change >2-fold in
either direction was considered “differentially expressed.” Gene expression analysis revealed
distinct differences in gene expression in MU cells compared with EC (665 genes), EC and
SCC (1673 genes). Enrichment analysis confirmed that pathways most affected included
1) elevation of genes associated with extracellular matrix organization/degradation, 2)
activation of DNA damage, and 3) activation of cytokine signaling. Our analysis revealed
two key insights about chronic wound microenvironment conducive to ulceration. First,
in EC vs MU comparison, downregulation of COL and MMP families suggests chronically
impaired extracellular matrix turnover giving rise to a fibrotic microenvironment. Second,
in SCC vs MU comparison, dysregulation of cadherin-mediated cell–cell adhesions is
suggestive of epithelial-to-mesenchymal transitions, similar to those during development.
Acquisition of epithelial-to-mesenchymal transition may underlie the high metastatic
rate in MU tumors. Taken together, this sheds light on mechanisms that underlie the
divergent clinical features of these cutaneous cancers.
Objective: Current methods for evaluating scar tissue volume following burns have shortcomings. T... more Objective: Current methods for evaluating scar tissue volume following burns have shortcomings. The Vancouver Burn Scar scale is subjective, leading to a high variability in assessment. Although histological assessment via punch biopsy can discriminate between the different layers of skin, such an approach is invasive, inefficient, and detrimental to patient experience and wound healing. This study investigates the accuracy of high-frequency ultrasonography, a non-invasive alternative to histology, for measuring dermal and epidermal thickness in scar tissue. Methods: Scar thicknesses of 10 patients following burns were assessed using a 2-D high-frequency ultrasound probe. The scars were then biopsied using a circular 4mm punch biopsy for histological assessment. Dermal, epidermal, and total thickness of the scar tissue was measured using ultrasound and histology, and correlations between the two measurements were calculated. Results: There was not a strong correlation between ultrasound measurement and histological analysis for epidermal, dermal, and total thickness (Spearman's rank correlation of À0.1223, À0.6242, and À0.6242) of scar tissue. Conclusions: Measurements of scar thickness using high-frequency ultrasonography did not recapitulate the in vivo dermal, epidermal and total thickness. Based on these findings, strategies for further optimization of 2-D ultrasonography is discussed before clinical and research use.
RE: “Ultrasound is a reproducible and valid tool for
measuring scar height in children with burn ... more RE: “Ultrasound is a reproducible and valid tool for
measuring scar height in children with burn scars: A
cross-sectional study of the psychometric properties
and utility of the ultrasound and 3D camera” by
M. Simons, E. Gee Kee, R. Kimble, Z. Tyack [Burns,
(2017) In press]
Peripheral nerve injury affects 2.8% of trauma patients with severe cases often resulting in long... more Peripheral nerve injury affects 2.8% of trauma patients with severe cases often resulting in long-lived permanent disability, despite nerve repair surgery. Autologous Schwann cell (SC) therapy currently provides an exciting avenue for improved outcomes for these patients, particularly with the possibility to derive SCs from easily-accessible adult skin. However, due to current challenges regarding the efficient expansion of these cells, further optimization is required before they can be seriously considered for clinical application. Here, a microcarrier-based bioreactor system is proposed as a means to scale-up large numbers of adult skin-derived SCs for transplantation into the injured nerve. Bioprocessing parameters that allow for the expansion of adult rodent SCs have been identified, whilst maintaining similar rates of proliferation (as compared to static-grown SCs), expression of SC markers, and, importantly, their capacity to myelinate axons following transplant into the injured sciatic nerve. The same bioprocessing parameters can be applied to SCs derived from adult human skin, and like rodent cells, they sustain their prolif-erative potential and expression of SC markers. Taken together, this dataset demonstrates the basis for a scalable bioprocess for the production of SCs, an important step towards clinical use of these cells as an adjunct therapy for nerve repair.
Cell-based therapies have recently been the focus of much research to enhance skin wound healing.... more Cell-based therapies have recently been the focus of much research to enhance skin wound healing. An important challenge will be to develop vehicles for cell delivery that promote survival and uniform distribution of cells across the wound bed. These systems should be stiff enough to facilitate handling, whilst soft enough to limit damage to newly synthesized wound tissue and minimize patient discomfort. Herein, we developed several novel modifiable nanofibre scaffolds comprised of Poly (ε-caprolactone) (PCL) and gelatin (GE). We asked whether they could be used as a functional receptacle for adult human Skin-derived Precursor Cells (hSKPs) and how naked scaffolds impact endogenous skin wound healing. PCL and GE were electrospun in a single facile solvent to create composite scaffolds and displayed unique morphological and mechanical properties. After seeding with adult hSKPs, deposition of extracellular matrix proteins and sulphated glycosaminoglycans was found to be enhanced in composite grafts. Moreover, composite scaffolds exhibited significantly higher cell proliferation, greater cell spreading and integration within the nanofiber mats. Transplantation of acellular scaffolds into wounds revealed scaffolds exhibited improvement in dermal-epidermal thickness, axonal density and collagen deposition. These results demonstrate that PCL-based nanofiber scaffolds show promise as a cell delivery system for wound healing. Besides providing a physical barrier that prevents pathologic infection, skin also performs a range of vital functions that maintain hydration, thermoregulation and body metabolism. Severe skin injury, such as burns and chronic non-healing wounds, result in lifelong functional impairment and, due to their need for chronic medical care, represent a substantial burden on healthcare. It is estimated that there are 6.5 million patients with chronic wounds in the United States alone, costing US$25 billion annually 1. In particular, full thickness burns, in which both the epidermal and dermal compartments are damaged, are unable to repair to their full capacity 2. Mammalian wound healing has evolved in favor of rapid closure, resulting in dysfunctional fibrotic scars. One promising approach to promote regeneration whilst minimizing scar is to engineer the local environment to promote coordinated cellular infiltration, organized deposition of extracellular matrix (ECM) and to provide instructive cues to promote regeneration of neodermis and appendage formation when combined with competent dermal cells. An ideal cell scaffold should resemble the native extracellular matrix and be capable of supporting cell adhesion, proliferation and maturation. Electrospun mats have the potential to mimic the dermal ECM and
Burns : journal of the International Society for Burn Injuries, Jan 18, 2017
Current methods for evaluating scar tissue volume following burns have shortcomings. The Vancouve... more Current methods for evaluating scar tissue volume following burns have shortcomings. The Vancouver Burn Scar scale is subjective, leading to a high variability in assessment. Although histological assessment via punch biopsy can discriminate between the different layers of skin, such an approach is invasive, inefficient, and detrimental to patient experience and wound healing. This study investigates the accuracy of high-frequency ultrasonography, a non-invasive alternative to histology, for measuring dermal and epidermal thickness in scar tissue. Scar thicknesses of 10 patients following burns were assessed using a 2-D high-frequency ultrasound probe. The scars were then biopsied using a circular 4mm punch biopsy for histological assessment. Dermal, epidermal, and total thickness of the scar tissue was measured using ultrasound and histology, and correlations between the two measurements were calculated. There was not a strong correlation between ultrasound measurement and histolog...
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Papers by Natacha Agabalyan
cause is unhealed burn injuries. This results in well-differentiated squamous cell carcinoma
(SCC). This study aimed to elucidate transcriptional changes leading to malignancy by
investigating differentially expressed genes in squamous cells present in a SCC compared
with MU. MU tumor cells were isolated from histologically confirmed biopsy of SCC
within an unhealed burn scar. Epithelial cells (ECs) adjacent to the tumor were co-isolated
and a SCC cell line was commercially purchased. mRNA from all three samples was isolated
and its expression was quantified using RNASeq. Threshold of log2fold change >2-fold in
either direction was considered “differentially expressed.” Gene expression analysis revealed
distinct differences in gene expression in MU cells compared with EC (665 genes), EC and
SCC (1673 genes). Enrichment analysis confirmed that pathways most affected included
1) elevation of genes associated with extracellular matrix organization/degradation, 2)
activation of DNA damage, and 3) activation of cytokine signaling. Our analysis revealed
two key insights about chronic wound microenvironment conducive to ulceration. First,
in EC vs MU comparison, downregulation of COL and MMP families suggests chronically
impaired extracellular matrix turnover giving rise to a fibrotic microenvironment. Second,
in SCC vs MU comparison, dysregulation of cadherin-mediated cell–cell adhesions is
suggestive of epithelial-to-mesenchymal transitions, similar to those during development.
Acquisition of epithelial-to-mesenchymal transition may underlie the high metastatic
rate in MU tumors. Taken together, this sheds light on mechanisms that underlie the
divergent clinical features of these cutaneous cancers.
measuring scar height in children with burn scars: A
cross-sectional study of the psychometric properties
and utility of the ultrasound and 3D camera” by
M. Simons, E. Gee Kee, R. Kimble, Z. Tyack [Burns,
(2017) In press]
cause is unhealed burn injuries. This results in well-differentiated squamous cell carcinoma
(SCC). This study aimed to elucidate transcriptional changes leading to malignancy by
investigating differentially expressed genes in squamous cells present in a SCC compared
with MU. MU tumor cells were isolated from histologically confirmed biopsy of SCC
within an unhealed burn scar. Epithelial cells (ECs) adjacent to the tumor were co-isolated
and a SCC cell line was commercially purchased. mRNA from all three samples was isolated
and its expression was quantified using RNASeq. Threshold of log2fold change >2-fold in
either direction was considered “differentially expressed.” Gene expression analysis revealed
distinct differences in gene expression in MU cells compared with EC (665 genes), EC and
SCC (1673 genes). Enrichment analysis confirmed that pathways most affected included
1) elevation of genes associated with extracellular matrix organization/degradation, 2)
activation of DNA damage, and 3) activation of cytokine signaling. Our analysis revealed
two key insights about chronic wound microenvironment conducive to ulceration. First,
in EC vs MU comparison, downregulation of COL and MMP families suggests chronically
impaired extracellular matrix turnover giving rise to a fibrotic microenvironment. Second,
in SCC vs MU comparison, dysregulation of cadherin-mediated cell–cell adhesions is
suggestive of epithelial-to-mesenchymal transitions, similar to those during development.
Acquisition of epithelial-to-mesenchymal transition may underlie the high metastatic
rate in MU tumors. Taken together, this sheds light on mechanisms that underlie the
divergent clinical features of these cutaneous cancers.
measuring scar height in children with burn scars: A
cross-sectional study of the psychometric properties
and utility of the ultrasound and 3D camera” by
M. Simons, E. Gee Kee, R. Kimble, Z. Tyack [Burns,
(2017) In press]