New insights into balancing wound healing and scarless skin repair

Zhou, Shengxi; Xie, Mengbo; Su, Juanjuan; Cai, Bingjie; Li, Jingan; Zhang, Kun

doi:10.1177/20417314231185848

Cited by 16 publications

(3 citation statements)

References 228 publications

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“…We show for the first time the complex and dynamic immune signature of early responses to lentectomy in these two newt species, with upregulation of transcripts involved in inflammation, ECM remodeling, pattern recognition, macrophages/monocytes, vascular development, complement activation, and angiogenesis. Both in acute and chronic wound healing of multiple tissues and species, macrophages display direct and indirect roles in hypertrophic scar formation versus scarless repair, as they can modulate fibroblast proliferation, myofibroblast differentiation and remodeling processes such as collagen deposition [ 93 , 111 – 114 ]. The early upregulation of anti- and pro-inflammatory transcripts is similar to that reported in other tissues in regeneration-competent amphibian species [ 13 , 16 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

Macrophages modulate fibrosis during newt lens regeneration

Tsissios,

Sallese,

Perez-Estrada

et al. 2024

Stem Cell Res Ther

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Background Previous studies have suggested that macrophages are present during lens regeneration in newts, but their role in the process is yet to be elucidated. Methods Here we generated a transgenic reporter line using the newt, Pleurodeles waltl, that traces macrophages during lens regeneration. Furthermore, we assessed early changes in gene expression during lens regeneration using two newt species, Notophthalmus viridescens and Pleurodeles waltl. Finally, we used clodronate liposomes to deplete macrophages during lens regeneration in both species and tested the effect of a subsequent secondary injury after macrophage recovery. Results Macrophage depletion abrogated lens regeneration, induced the formation of scar-like tissue, led to inflammation, decreased iris pigment epithelial cell (iPEC) proliferation, and increased rates of apoptosis in the eye. Some of these phenotypes persisted throughout the last observation period of 100 days and could be attenuated by exogenous FGF2 administration. A distinct transcript profile encoding acute inflammatory effectors was established for the dorsal iris. Reinjury of the newt eye alleviated the effects of macrophage depletion, including the resolution of scar-like tissue, and re-initiated the regeneration process. Conclusions Together, our findings highlight the importance of macrophages for facilitating a pro-regenerative environment in the newt eye by regulating fibrotic responses, modulating the overall inflammatory landscape, and maintaining the proper balance of early proliferation and late apoptosis of the iPECs.

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Section: Discussionmentioning

confidence: 99%

Macrophages modulate fibrosis during newt lens regeneration

Tsissios,

Sallese,

Perez-Estrada

et al. 2024

Stem Cell Res Ther

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“…Acute or chronic wound healing caused by burns and trauma is a major medical and social problem, and the mechanisms involved in wound repair process need to be elucidated. 17 Wounds in oral mucosa are able to heal more rapidly and without scar than skin wounds though the factors in basal state of oral mucosa; 10 , 12 however, the potential factors promoting rapidly wound healing in basal state still need to be explored. Here, we identified the gene module and pathways enriched in basal state of oral mucosa.…”

Section: Discussionmentioning

confidence: 99%

Identification of IGF2 promotes skin wound healing by co‐expression analysis

Liu,

Teng,

et al. 2024

International Wound Journal

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Oral mucosa is an ideal model for studying scarless wound healing. Researchers have shown that the key factors which promote scarless wound healing already exist in basal state of oral mucosa. Thus, to identify the other potential factors in basal state of oral mucosa will benefit to skin wound healing. In this study, we identified eight gene modules enriched in wound healing stages of human skin and oral mucosa through co‐expression analysis, among which the module M8 was only module enriched in basal state of oral mucosa, indicating that the genes in module M8 may have key factors mediating scarless wound healing. Through bioinformatic analysis of genes in module M8, we found IGF2 may be the key factor mediating scarless wound healing of oral mucosa. Then, we purified IGF2 protein by prokaryotic expression, and we found that IGF2 could promote the proliferation and migration of HaCaT cells. Moreover, IGF2 promoted wound re‐epithelialization and accelerated wound healing in a full‐thickness skin wound model. Our findings identified IGF2 as a factor to promote skin wound healing which provide a potential target for wound healing therapy in clinic.

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“…Several crucial cellular behaviors, including re‐epithelialization, angiogenesis, and fibroblast activation, occur during the proliferative phase 126,127 . Recent studies have demonstrated that natural sEVs may exert therapeutic effects by enhancing the proliferation and migration, 23,128 and mitigating oxidative stress‐induced senescence of HUVECs, 129 or inhibiting the apoptosis and recovering cellular function of HaCaTs 130 .…”

Section: Applications Of Engineered Sevs In Diabetic Wound Managementmentioning

confidence: 99%

Small extracellular vesicles: Yields, functionalization and applications in diabetic wound management

Liu,

Wei,

Sun

et al. 2023

Interdisciplinary Medicine

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Diabetic wounds have imposed a significant burden on both patients and society with prolonged healing processes hindered by dysfunctional skin repair cells. Small extracellular vesicles (sEVs), as the important media for intercellular communications, show promising therapeutic potential in treating diabetic wounds by restoring cellular functions. However, low yields and limited bio‐function of sEVs greatly challenge their large‐scale clinical use. Here, we briefly overview the biogenesis and cellular uptake of sEVs, emphasize current advances in improving the yields of sEVs and optimizing the function of sEVs with engineering approaches, and summarize the applications of engineered sEVs in diabetic wound treatment. Furthermore, the undissolved issues during the clinical transformation of engineered sEVs are also discussed. This critical review aims to provide meaningful guidance for future applications of engineered sEVs in the management of diabetic wounds.

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New insights into balancing wound healing and scarless skin repair

Cited by 16 publications

References 228 publications

Macrophages modulate fibrosis during newt lens regeneration

Macrophages modulate fibrosis during newt lens regeneration

Identification of IGF2 promotes skin wound healing by co‐expression analysis

Small extracellular vesicles: Yields, functionalization and applications in diabetic wound management

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