Regeneration of skin appendages and nerves: current status and further challenges

Weng, Tingting; Wu, Pan; Zhang, Wei; Zheng, Yurong; Li, Qiong; Jin, Ronghua; Chen, Haojiao; You, Chuangang; Guo, Songxue; Han, Chunmao; Wang, Xingang

doi:10.1186/s12967-020-02248-5

Cited by 91 publications

(69 citation statements)

References 134 publications

(154 reference statements)

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“…It constitutes a protective barrier towards outer world, and thus is susceptible to damage resulting from inter alia burns, surgical procedures, or diabetic ulcers. To enhance wound repair and regeneration, many tissue-engineered skin products have been developed [232][233][234][235][236]. In general, biomaterials for treatment of skin injuries can be divided on two groups including wound dressings and skin substitutes ( Table 1).…”

Section: Skin Tementioning

confidence: 99%

“…In other words, they should have optimal water vapor transmission ratio (WVTR) and great ability to absorb wound exudate (if it occurs). Moreover, modern wound dressings should also accelerate wound healing [232][233][234]236,[242][243][244][245]. Progress in the field of engineering of biomaterials has led to the development of many promising wound dressings.…”

Section: Hacat and Bj Cell Lines/ Micementioning

confidence: 99%

“…Skin substitutes should also possess mechanical parameters close to those of natural skin (inter alia Young's modulus. ranging 60-850 kPa) [232][233][234]236,[242][243][244][245]248]. Nowadays, there is no biomaterial that meets all these criteria.…”

Section: Hacat and Bj Cell Lines/ Micementioning

confidence: 99%

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Proteins and Peptides as Important Modifiers of the Polymer Scaffolds for Tissue Engineering Applications—A Review

2020

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Polymer scaffolds constitute a very interesting strategy for tissue engineering. Even though they are generally non-toxic, in some cases, they may not provide suitable support for cell adhesion, proliferation, and differentiation, which decelerates tissue regeneration. To improve biological properties, scaffolds are frequently enriched with bioactive molecules, inter alia extracellular matrix proteins, adhesive peptides, growth factors, hormones, and cytokines. Although there are many papers describing synthesis and properties of polymer scaffolds enriched with proteins or peptides, few reviews comprehensively summarize these bioactive molecules. Thus, this review presents the current knowledge about the most important proteins and peptides used for modification of polymer scaffolds for tissue engineering. This paper also describes the influence of addition of proteins and peptides on physicochemical, mechanical, and biological properties of polymer scaffolds. Moreover, this article sums up the major applications of some biodegradable natural and synthetic polymer scaffolds modified with proteins and peptides, which have been developed within the past five years.

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Section: Skin Tementioning

confidence: 99%

Section: Hacat and Bj Cell Lines/ Micementioning

confidence: 99%

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Proteins and Peptides as Important Modifiers of the Polymer Scaffolds for Tissue Engineering Applications—A Review

2020

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“…The ultimate goal of tissue engineering skin is to rapidly produce a construct that offers the complete regeneration of functional skin, including all layers (epidermis, dermis, and subcutaneous tissue), all skin appendages (hair follicles, sweat glands, and sensory organs), and a functional vascular and nerve network [6,58]. Our system still has a lot of room to develop further to reach the above goals since we have not observed any formation of sweat glands or a fat layer in our grafts so far.…”

Section: Discussionmentioning

confidence: 99%

Early-stage bilayer tissue-engineered skin substitute formed by adult skin progenitor cells produces an improved skin structure in vivo

et al. 2020

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Background In recent years, significant progress has been made in developing highly complex tissue-engineered skin substitutes (TESSs) for wound healing. However, the lack of skin appendages, such as hair follicles and sweat glands, and the time required, are two major limitations that hinder its broad application in the clinic. Therefore, it is necessary to develop a competent TESS in a short time to meet the needs for clinical applications. Methods Adult scalp dermal progenitor cells and epidermal stem cells together with type I collagen as a scaffold material were used to reconstitute bilayer TESSs in vitro. TESSs at 4 different culture times (5, 9, 14, and 21 days) were collected and then grafted onto full-thickness wounds created in the dorsal skin of athymic nude/nude mice. The skin specimens formed from grafted TESSs were collected 4 and 8 weeks later and then evaluated for their structure, cell organization, differentiation status, vascularization, and formation of appendages by histological analysis, immunohistochemistry, and immunofluorescent staining. Results Early-stage bilayer TESSs after transplantation had a better efficiency of grafting. A normal structure of stratified epidermis containing multiple differentiated layers of keratinocytes was formed in all grafts from both early-stage and late-stage TESSs, but higher levels of the proliferation marker Ki-67 and the epidermal progenitor marker p63 were found in the epidermis formed from early-stage TESSs. Interestingly, the transplantation of early-stage TESSs produced a thicker dermis that contained more vimentin- and CD31-positive cells, and importantly, hair follicle formation was only observed in the skin grafted from early-stage TESSs. Finally, early-stage TESSs expressed high levels of p63 but had low expression levels of genes involved in the activation of the apoptotic pathway compared to the late-stage TESSs in vitro. Conclusions Early-stage bilayer TESSs reconstituted from skin progenitor cells contained more competent cells with less activation of the apoptotic pathway and produced a better skin structure, including hair follicles associated with sebaceous glands, after transplantation, which should potentially provide better wound healing when applied in the clinic in the future.

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“…Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) exist in the Wharton's jelly and perivascular area of the human umbilical cord and hold promise for the eld of regenerative medicine because of their strong capacity to regenerate injured tissues indirectly through growth factor secretion and immunomodulation. In particular, several studies have found that transplantation of WJ-MSCs can signi cantly increase the number of microvessels at the injury site, improve local blood ow perfusion, accelerate wound healing, and promote organ function recovery [2][3][4][5] . Our previous studies showed that WJ-MSCs can ameliorate damaged human endometrial stromal cells (ESCs) [6,7] , thus, indicating that it is possible to use WJ-MSCs to repair endometrial damage.…”

Section: Introductionmentioning

confidence: 99%

Circ6401, a novel circular RNA, is implicated in repair of the damaged endometrium by Wharton’s jelly-derived mesenchymal stem cells through regulation of the miR-29b-1-5p/RAP1B axis

Shi

Sun

Wang

et al. 2020

Preprint

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Background Accumulating evidence indicates that mesenchymal stem cells (MSCs) exert tissue repair effects and therapeutic angiogenesis through their noncoding RNAs (ncRNAs). Our previous studies showed that MSCs derived from Wharton’s jelly (WJ-MSCs) can ameliorate damaged human endometrium by promoting angiogenesis. There is limited information on the functions and mechanism of ncRNAs in MSC-induced endometrial repair, and additional studies are needed for more insights.Methods Here, WJ-MSCs were cocultured with or without endometrial stromal cells (ESCs) damaged by mifepristone (cocultured group versus non-cocultured group). TUNEL staining assays, EdU proliferation assays, flow cytometry apoptosis assays, and western blot assays were performed to observe the reparative effect of WJ-MSCs on damaged ESCs. Subsequently, circular RNA (circRNA) and microRNA microarrays were performed between the two groups. A subset of top upregulated circRNAs was validated by qRT-PCR. The functions of circ6401 (hsa_circ_0006401) in WJ-MSCs were investigated using lentivirus-mediated circRNA overexpression assays. The subcellular localization of circ6401 and miR-29b-1-5p in WJ-MSCs was identified by double RNA fluorescence in situ hybridization. Dual-luciferase reporter assays and western blot assays were performed to elucidate the regulatory mechanisms among circ6401, miR-29b-1-5p, and RAP1B.Results WJ-MSCs significantly improved ESC proliferation and upregulated the expression of vascular angiogenesis markers. Circ6401 was upregulated in WJ-MSCs cocultured with damaged ESCs, while miR-29b-1-5p was significantly downregulated. Furthermore, circ6401 was found to bind to miR-29b-1-5p and prevent it from decreasing the level of RAP1B, a crucial protein involved in the VEGF signaling pathway, which promoted angiogenesis and stimulated the proliferation of ESCs.Conclusions Our results showed the abundance and regulation profiles of ncRNAs of WJ-MSCs during repair of damaged ESCs, and for the first time, clarified the underlying mechanism by which circ6401 promotes endometrial repair by WJ-MSCs; thus, demonstrating that circ6401 may serve as a potential therapeutic target.

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Regeneration of skin appendages and nerves: current status and further challenges

Cited by 91 publications

References 134 publications

Proteins and Peptides as Important Modifiers of the Polymer Scaffolds for Tissue Engineering Applications—A Review

Proteins and Peptides as Important Modifiers of the Polymer Scaffolds for Tissue Engineering Applications—A Review

Early-stage bilayer tissue-engineered skin substitute formed by adult skin progenitor cells produces an improved skin structure in vivo

Circ6401, a novel circular RNA, is implicated in repair of the damaged endometrium by Wharton’s jelly-derived mesenchymal stem cells through regulation of the miR-29b-1-5p/RAP1B axis

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