Transplantation of an LGR6+ Epithelial Stem Cell–Enriched Scaffold for Repair of Full-Thickness Soft-Tissue Defects

Lough, Denver M.; Wetter, Nathan; Madsen, Christopher; Reichensperger, Joel; Cosenza, Nicole; Cox, Lisa; Harrison, Carrie; Neumeister, Michael W.

doi:10.1097/01.prs.0000475761.09451.00

Cited by 24 publications

(17 citation statements)

References 26 publications

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“…Hair follicle stem cells in the bulge region can be identified by many proteins, such as K15, Lgr5, and CD34 ( Cotsarelis et al, 1990 ; Ito et al, 2005 ; Plikus et al, 2012 ). Lgr6 is one of the earliest placode markers and its stem cells located in the hair follicle isthmus are thought to give rise to hair follicle, sebaceous gland, and inter-follicular epidermal lineage, and have been verified to promote WIHN ( Snippert et al, 2010 ; Lough et al, 2016 ). Lrig1 + stem cells tend to contribute predominantly to infundibulum and sebaceous gland lineages and only occasionally to the inter-follicular epidermis ( Jensen et al, 2009 ).…”

Section: Discussionmentioning

confidence: 99%

IL-36α Promoted Wound Induced Hair Follicle Neogenesis via Hair Follicle Stem/Progenitor Cell Proliferation

Gong

Xiao

et al. 2020

Front. Cell Dev. Biol.

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Background Wound-induced hair follicle neogenesis (WIHN) is a phenomenon of hair neogenesis that occurs at the center of a scar when the wound area is sufficiently large. Neogenic hair follicles are separated from the pre-existing follicles at the wound edge by a hairless circular region. This WIHN study provides a unique model for developing treatments for hair loss and deciphering the mechanisms underlying organogenesis in adult mammals. Methods The skin of a mouse was wounded by excising a 1.5 × 1.5 cm 2 square of full-thickness dorsal skin. iTRAQ technology was used to screen proteins differentially expressed between the inner and outer scar areas in a mouse model of WIHN, on post-wounding day 15, to identify the regulators of WIHN. Owing to the overexpression of interleukin-36α (IL-36α) in the de novo hair follicle growth area, the regulating effect of IL-36α overexpression in WIHN was investigated. Hair follicle stem/progenitor cells were counted by flow cytometry while the expression of hair follicle stem/progenitor cell markers ( Lgr5, Lgr6, Lrig1, K15 , and CD34 ) and that of Wnt/β-catenin and IL-6/STAT3 pathway intermediaries was detected by qPCR and western blotting. Results We found that wounding induced IL-36α expression. Incorporation of recombinant murine IL-36α (mrIL-36α) into murine skin wounds resulted in a greater number of regenerated hair follicles ( p < 0.005) and a faster healing rate. The expression of hair follicle stem/progenitor cell markers was upregulated in the mrIL-36α-injected site ( p < 0.05). Additionally, mrIL-36α upregulated the IL-6/STAT3 pathway intermediaries. Conclusion IL-36α is upregulated in de novo hair follicle growth areas and can promote wound epithelialization and WIHN.

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Section: Discussionmentioning

confidence: 99%

IL-36α Promoted Wound Induced Hair Follicle Neogenesis via Hair Follicle Stem/Progenitor Cell Proliferation

Gong

Xiao

et al. 2020

Front. Cell Dev. Biol.

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“…MSC-collagen treated mice also had significantly more expression of VEGF and more intense early expression of MMP-9 compared to collagen treatment without MSCs, indicating a possible mechanism of MSCs’ effects on wound healing [ 64 ]. Similarly, other stem cells such as ADSCs and Leucine Rich Repeat Containing G Protein-Coupled Receptor 6 (LGR6+) epithelial stem cells have been delivered to wounds using collagen scaffolds [ 65 , 66 ].…”

Section: Polymer-based Biomaterials For Stem Cell Delivery For Regmentioning

confidence: 99%

Stem Cells and Engineered Scaffolds for Regenerative Wound Healing

Dash

Lin

et al. 2018

Bioengineering

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The normal wound healing process involves a well-organized cascade of biological pathways and any failure in this process leads to wounds becoming chronic. Non-healing wounds are a burden on healthcare systems and set to increase with aging population and growing incidences of obesity and diabetes. Stem cell-based therapies have the potential to heal chronic wounds but have so far seen little success in the clinic. Current research has been focused on using polymeric biomaterial systems that can act as a niche for these stem cells to improve their survival and paracrine activity that would eventually promote wound healing. Furthermore, different modification strategies have been developed to improve stem cell survival and differentiation, ultimately promoting regenerative wound healing. This review focuses on advanced polymeric scaffolds that have been used to deliver stem cells and have been tested for their efficiency in preclinical animal models of wounds.

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“…Manipulation of LGR+ cells in regenerative medicine applications within other fields has been demonstrated: in vitro expansion of Lgr + cells and organoids via RSPO stimulation has been shown in liver and intestinal cells, (94)(95)(96) and direct treatment with LGR+ cells has been attempted in dermatological wounds, where these cells appear to promote vascularization and epithelialization during the healing process. (76) With multiple studies demonstrating how Wnt treatment can be harnessed to modulate bone formation and improve bone healing, it is likely that the use of R-spondins as agonists for LGR-mediated Wnt signaling and induction of LGR+ cells holds strong therapeutic promise.…”

Section: Discussionmentioning

confidence: 99%

“…(39,40) This prominent focus on LGR6 in studies of osteogenesis as opposed to other LGR family members is not surprising, as LGR6 has been specifically implicated in regenerative processes of other tissues. (1,6,7,76,77) LGRs in Dental Cells and Tissues…”

Section: Lgrs In Skeletal Remodelingmentioning

confidence: 99%

LGRs in Skeletal Tissues: An Emerging Role for Wnt‐Associated Adult Stem Cell Markers in Bone

Doherty

Sanjay

2020

JBMR Plus

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Leucine-rich repeat-containing G protein-coupled receptors (LGRs) are adult stem cell markers that have been described across various stem cell niches, and expression of LGRs and their corresponding ligands (R-spondins) has now been reported in multiple bonespecific cell types. The skeleton harbors elusive somatic stem cell populations that are exceedingly compartment-specific and under tight regulation from various signaling pathways. Skeletal progenitors give rise to multiple tissues during development and during regenerative processes of bone, requiring postnatal endochondral and intramembranous ossification. The relevance of LGRs and the LGR/R-spondin ligand interaction in bone and tooth biology is becoming increasingly appreciated. LGRs may define specific stem cell and progenitor populations and their behavior during both development and regeneration, and their role as Wnt-associated receptors with specific ligands poses these proteins as unique therapeutic targets via potential R-spondin agonism. This review seeks to outline the current literature on LGRs in the context of bone and its associated tissues, and points to key future directions for studying the functional role of LGRs and ligands in skeletal biology.

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Transplantation of an LGR6+ Epithelial Stem Cell–Enriched Scaffold for Repair of Full-Thickness Soft-Tissue Defects

Abstract: Therapeutic, V.

Cited by 24 publications

References 26 publications

IL-36α Promoted Wound Induced Hair Follicle Neogenesis via Hair Follicle Stem/Progenitor Cell Proliferation

IL-36α Promoted Wound Induced Hair Follicle Neogenesis via Hair Follicle Stem/Progenitor Cell Proliferation

Stem Cells and Engineered Scaffolds for Regenerative Wound Healing

LGRs in Skeletal Tissues: An Emerging Role for Wnt‐Associated Adult Stem Cell Markers in Bone

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