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Biomedicines
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Biomedical Potential of Stem Cells in Skin Regeneration and Wound...
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Biomedical Potential of Stem Cells in Skin Regeneration and Wound Healing

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Gene and Cell Therapy".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 13418

Special Issue Editor

Dr. Agnes S. Klar

E-Mail Website
Guest Editor
Tissue Biology Research Unit, University Children’s Hospital Zurich, University of Zurich, Schlieren, Switzerland
Interests: wound healing; vascular biology; skin regeneration; biomaterials; tissue engineering; immunomodulation

Special Issue Information

Dear Colleagues,

The skin is the largest organ of the human body and acts as a barrier against infection, along with many other functions. Although tremendous progress has been made, large full-thickness skin traumas such as burns affecting all skin layers and its appendages are still associated with mortality due to a low availability of donor skin areas. Further, skin regeneration is often impaired due to the limited regenerative capacity of adult skin cells, which heal a wound without generating de novo skin appendages and causing fibrosis and scarring. Importantly, compromised function of local and systemic stem cells and progenitors also play a considerable role in the pathology of chronic wounds. Hence, adult stem cells are considered to be potential candidates for novel regenerative therapies in numerous skin pathologies.

Currently, stem-cell-based therapies applying dermal and epidermal as well as mesenchymal stem cells, embryonic, and induced pluripotent stem cells are becoming one of the most explored potential therapeutic strategies to facilitate a complete regeneration of skin and its appendages in cutaneous wound healing. In this Special Issue, we will focus on the biomedical potential of adult stem cells harvested from different tissue as tools for cell and scaffold-based therapies for chronic wounds and other skin disorders. This Special Issue aims to present emerging concepts and novel efficacious therapies for various skin pathologies.

We cordially invite you to contribute your original research to this exciting Special Issue of Biomedicines.

Dr. Agnes Klar
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • bio-engineered skin products
  • vascularization
  • wound repair
  • stem-cell-based therapies
  • stem cell activation
  • inflammatory tissue response
  • stem cell senescence

Published Papers (4 papers)

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Research

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19 pages, 3844 KiB  
Article
Adipose-Derived Stromal Cells within a Gelatin Matrix Acquire Enhanced Regenerative and Angiogenic Properties: A Pre-Clinical Study for Application to Chronic Wounds
by Nicolo Costantino Brembilla, Ali Modarressi, Dominik André-Lévigne, Estelle Brioudes, Florian Lanza, Hubert Vuagnat, Stéphane Durual, Laurine Marger, Wolf-Henning Boehncke, Karl-Heinz Krause and Olivier Preynat-Seauve
Biomedicines 2023, 11(3), 987; https://doi.org/10.3390/biomedicines11030987 - 22 Mar 2023
Cited by 1 | Viewed by 1332
Abstract
This study evaluates the influence of a gelatin sponge on adipose-derived stromal cells (ASC). Transcriptomic data revealed that, compared to ASC in a monolayer, a cross-linked porcine gelatin sponge strongly influences the transcriptome of ASC. Wound healing genes were massively regulated, notably with [...] Read more.
This study evaluates the influence of a gelatin sponge on adipose-derived stromal cells (ASC). Transcriptomic data revealed that, compared to ASC in a monolayer, a cross-linked porcine gelatin sponge strongly influences the transcriptome of ASC. Wound healing genes were massively regulated, notably with the inflammatory and angiogenic factors. Proteomics on conditioned media showed that gelatin also acted as a concentrator and reservoir of the regenerative ASC secretome. This secretome promoted fibroblast survival and epithelialization, and significantly increased the migration and tubular assembly of endothelial cells within fibronectin. ASC in gelatin on a chick chorioallantoic membrane were more connected to vessels than an empty sponge, confirming an increased angiogenesis in vivo. No tumor formation was observed in immunodeficient nude mice to which an ASC gelatin sponge was transplanted subcutaneously. Finally, ASC in a gelatin sponge prepared from outbred rats accelerated closure and re-vascularization of ischemic wounds in the footpads of rats. In conclusion, we provide here preclinical evidence that a cross-linked porcine gelatin sponge is an optimal carrier to concentrate and increase the regenerative activity of ASC, notably angiogenic. This formulation of ASC represents an optimal, convenient and clinically compliant option for the delivery of ASC on ischemic wounds. Full article
(This article belongs to the Special Issue Biomedical Potential of Stem Cells in Skin Regeneration and Wound Healing)
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19 pages, 52308 KiB  
Article
Expression Profile of CD157 Reveals Functional Heterogeneity of Capillaries in Human Dermal Skin
by Katarzyna Michalak-Micka, Dominic Rütsche, Lukas Johner, Ueli Moehrlen, Thomas Biedermann and Agnes S. Klar
Biomedicines 2022, 10(3), 676; https://doi.org/10.3390/biomedicines10030676 - 15 Mar 2022
Cited by 2 | Viewed by 2037
Abstract
CD157 acts as a receptor, regulating leukocyte trafficking and the binding of extracellular matrix components. However, the expression pattern and the role of CD157 in human blood (BEC) and the lymphatic endothelial cells (LEC) of human dermal microvascular cells (HDMEC), remain elusive. We [...] Read more.
CD157 acts as a receptor, regulating leukocyte trafficking and the binding of extracellular matrix components. However, the expression pattern and the role of CD157 in human blood (BEC) and the lymphatic endothelial cells (LEC) of human dermal microvascular cells (HDMEC), remain elusive. We demonstrated constitutive expression of CD157 on BEC and LEC, in fetal and juvenile/adult skin, in situ, as well as in isolated HDMEC. Interestingly, CD157 epitopes were mostly localized on BEC, co-expressing high levels of CD31 (CD31High), as compared to CD31Low BEC, whereas the podoplanin expression level on LEC did not affect CD157. Cultured HDMEC exhibited significantly higher numbers of CD157-positive LEC, as compared to BEC. Interestingly, separated CD157− and CD157+ HDMEC demonstrated no significant differences in clonal expansion in vitro, but they showed distinct expression levels of cell adhesion molecules, before and after cytokine stimulation in vitro. In particular, we proved the enhanced and specific adherence of CD11b-expressing human blood myeloid cells to CD157+ HDMEC fraction, using an in vitro immune-binding assay. Indeed, CD157 was also involved in chemotaxis and adhesion of CD11b/c monocytes/neutrophils in prevascularized dermo–epidermal skin substitutes (vascDESS) in vivo. Thus, our data attribute specific roles to endothelial CD157, in the regulation of innate immunity during inflammation. Full article
(This article belongs to the Special Issue Biomedical Potential of Stem Cells in Skin Regeneration and Wound Healing)
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17 pages, 6394 KiB  
Article
Differential Capability of Clinically Employed Dermal Regeneration Scaffolds to Support Vascularization for Tissue Bioengineering
by Chiara Agostinis, Mariagiulia Spazzapan, Roman Vuerich, Andrea Balduit, Chiara Stocco, Alessandro Mangogna, Giuseppe Ricci, Giovanni Papa, Serena Zacchigna and Roberta Bulla
Biomedicines 2021, 9(10), 1458; https://doi.org/10.3390/biomedicines9101458 - 13 Oct 2021
Cited by 7 | Viewed by 2302
Abstract
The loss of skin integrity has always represented a major challenge for clinicians dealing with dermal defects, such as ulcers (diabetic, vascular and chronic), postoncologic resections (i.e., radical vulvectomy) or dermatologic disorders. The introduction in recent decades of acellular dermal matrices (ADMs) supporting [...] Read more.
The loss of skin integrity has always represented a major challenge for clinicians dealing with dermal defects, such as ulcers (diabetic, vascular and chronic), postoncologic resections (i.e., radical vulvectomy) or dermatologic disorders. The introduction in recent decades of acellular dermal matrices (ADMs) supporting the repair and restoration of skin functionality represented a significant step toward achieving clean wound repair before performing skin grafts. Hard-to-heal ulcers generally depend on local ischemia and nonadequate vascularization. In this context, one possible innovative approach could be the prevascularization of matrices with vessel-forming cells (inosculation). This paper presents a comparative analysis of the most widely used dermal templates, i.e., Integra® Bilayer Matrix Wound Dressing, PELNAC®, PriMatrix® Dermal Repair Scaffold, Endoform® Natural Dermal Template, and Myriad Matrix®, testing their ability to be colonized by human adult dermal microvascular endothelial cells (ADMECs) and to induce and support angiogenesis in vitro and in vivo. By in vitro studies, we demonstrated that Integra® and PELNAC® possess superior pro-adhesive and pro-angiogenetic properties. Animal models allowed us to demonstrate the ability of preseeded ADMECs on Integra® to promote the engraftment, integration and vascularization of ADMs at the site of application. Full article
(This article belongs to the Special Issue Biomedical Potential of Stem Cells in Skin Regeneration and Wound Healing)
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Review

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41 pages, 8592 KiB  
Review
Immunomodulation of Skin Repair: Cell-Based Therapeutic Strategies for Skin Replacement (A Comprehensive Review)
by Shima Tavakoli, Marta A. Kisiel, Thomas Biedermann and Agnes S. Klar
Biomedicines 2022, 10(1), 118; https://doi.org/10.3390/biomedicines10010118 - 06 Jan 2022
Cited by 10 | Viewed by 5989
Abstract
The immune system has a crucial role in skin wound healing and the application of specific cell-laden immunomodulating biomaterials emerged as a possible treatment option to drive skin tissue regeneration. Cell-laden tissue-engineered skin substitutes have the ability to activate immune pathways, even in [...] Read more.
The immune system has a crucial role in skin wound healing and the application of specific cell-laden immunomodulating biomaterials emerged as a possible treatment option to drive skin tissue regeneration. Cell-laden tissue-engineered skin substitutes have the ability to activate immune pathways, even in the absence of other immune-stimulating signals. In particular, mesenchymal stem cells with their immunomodulatory properties can create a specific immune microenvironment to reduce inflammation, scarring, and support skin regeneration. This review presents an overview of current wound care techniques including skin tissue engineering and biomaterials as a novel and promising approach. We highlight the plasticity and different roles of immune cells, in particular macrophages during various stages of skin wound healing. These aspects are pivotal to promote the regeneration of nonhealing wounds such as ulcers in diabetic patients. We believe that a better understanding of the intrinsic immunomodulatory features of stem cells in implantable skin substitutes will lead to new translational opportunities. This, in turn, will improve skin tissue engineering and regenerative medicine applications. Full article
(This article belongs to the Special Issue Biomedical Potential of Stem Cells in Skin Regeneration and Wound Healing)
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