Implications of Extracellular Matrix Production by Adipose Tissue-Derived Stem Cells for Development of Wound Healing Therapies

Hyldig, Kathrine; Porsborg, Simone Riis; Pennisi, Cristian Pablo; Zachar, Vladimír; Fink, Trine

doi:10.3390/ijms18061167

Cited by 75 publications

(38 citation statements)

References 84 publications

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“…In injured sites, ADSCs were recruited and were migrated by increasing their expression of CXCR-4 molecules, which led to modulating the inflammatory phenotype of local immune cells to a healing anti-inflammatory one. Their presence was critical to drive the inflammatory profile of macrophages, T, B, and dendritic cells initiating, and thus the proliferation and remodeling phases of wound healing [51,52]. Their action was likely activated by TGF-β or GDF11 or both of them [53].…”

Section: Role Of the Microenvironment In Adscs Inductionmentioning

confidence: 99%

“…Allogenic fibroblasts were first used to support skin architecture by providing ECM protein secretion, but also by feeding surrounding skin cells by growth factors involved in cell proliferation and tissue regeneration. Using ADSCs within these skin substitutes have permitted the rapid reconstitution, more micro-vasculatures, more elasticity and better dermal cell compositions with high ECM secretion resulting in proliferation, and the remodeling phases of wound healing [52]. Skin has a more satisfying esthetic appearance and function, consequently overcoming the CEA limitations observed, such as recurrent open wounds and fragility, and the extensive ECM protein production leading to scar contractions [91].…”

Section: Adscs Issues Between Hopes and Limitsmentioning

confidence: 99%

“…Nevertheless, the more enriched secretome the growth factors and cytokines ADSCs are able to secrete makes them more advantageous in participating in skin cell biology and function. These growth factors were reported to autoactivate ADSCs and initiate the whole mechanisms involved in different phases of wound healing [52]. Indeed, ADSCs secretome is composed of proinflammatory and anti-inflammatory growth factors, fibroblasts growth factors including GDF11, TGF-β, b-FGF, VEGF, TLR2, TLR4, IL-10, and MMP involved directly in cell proliferation, and tissue repair and rejuvenation processes [61,111,[149][150][151][152].…”

Section: Summary and Perspectivesmentioning

confidence: 99%

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Hopes and Limits of Adipose-Derived Stem Cells (ADSCs) and Mesenchymal Stem Cells (MSCs) in Wound Healing

Mazini

Rochette

Admou

et al. 2020

IJMS

340

219

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Adipose tissue derived stem cells (ADSCs) are mesenchymal stem cells identified within subcutaneous tissue at the base of the hair follicle (dermal papilla cells), in the dermal sheets (dermal sheet cells), in interfollicular dermis, and in the hypodermis tissue. These cells are expected to play a major role in regulating skin regeneration and aging-associated morphologic disgraces and structural deficits. ADSCs are known to proliferate and differentiate into skin cells to repair damaged or dead cells, but also act by an autocrine and paracrine pathway to activate cell regeneration and the healing process. During wound healing, ADSCs have a great ability in migration to be recruited rapidly into wounded sites added to their differentiation towards dermal fibroblasts (DF), endothelial cells, and keratinocytes. Additionally, ADSCs and DFs are the major sources of the extracellular matrix (ECM) proteins involved in maintaining skin structure and function. Their interactions with skin cells are involved in regulating skin homeostasis and during healing. The evidence suggests that their secretomes ensure: (i) The change in macrophages inflammatory phenotype implicated in the inflammatory phase, (ii) the formation of new blood vessels, thus promoting angiogenesis by increasing endothelial cell differentiation and cell migration, and (iii) the formation of granulation tissues, skin cells, and ECM production, whereby proliferation and remodeling phases occur. These characteristics would be beneficial to therapeutic strategies in wound healing and skin aging and have driven more insights in many clinical investigations. Additionally, it was recently presented as the tool key in the new free-cell therapy in regenerative medicine. Nevertheless, ADSCs fulfill the general accepted criteria for cell-based therapies, but still need further investigations into their efficiency, taking into consideration the host-environment and patient-associated factors.

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Section: Role Of the Microenvironment In Adscs Inductionmentioning

confidence: 99%

Section: Adscs Issues Between Hopes and Limitsmentioning

confidence: 99%

Section: Summary and Perspectivesmentioning

confidence: 99%

See 1 more Smart Citation

Hopes and Limits of Adipose-Derived Stem Cells (ADSCs) and Mesenchymal Stem Cells (MSCs) in Wound Healing

Mazini

Rochette

Admou

et al. 2020

IJMS

340

219

View full text Add to dashboard Cite

show abstract

“…More importantly, delayed wound healing not only leads to increasing healthcare costs but also seriously impairs the quality of life in DM patients. Because the traditional therapies are often insufficient, a novel method to promote diabetic wound healing is of considerable interest at present (Hyldig et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

GMSC-Derived Exosomes Combined with a Chitosan/Silk Hydrogel Sponge Accelerates Wound Healing in a Diabetic Rat Skin Defect Model

et al. 2017

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Background: Delayed wound healing in diabetic patients is one of the most challenging complications in clinical medicine, as it poses a greater risk of gangrene, amputation and even death. Therefore, a novel method to promote diabetic wound healing is of considerable interest at present. Previous studies showed that injection of MSC-derived exosomes has beneficial effects on wound healing. In current studies, we aimed to isolate exosomes derived from gingival mesenchymal stem cells (GMSCs) and then loading them to the chitosan/silk hydrogel sponge to evaluate the effects of this novel non-invasive method on skin defects in diabetic rats.Methods: GMSCs were isolated from human gingival connective tissue and characterized by surface antigen analysis and in vitro multipotent differentiation. The cell supernatant was collected to isolate the exosomes. The exosomes were characterized by transmission electron microscopy, Western blot and size distribution analysis. The chitosan/silk-based hydrogel sponge was prepared using the freeze-drying method and then structural and physical properties were characterized. Then, the exosomes were added to the hydrogel and tested in a diabetic rat skin defect model. The effects were evaluated by wound area measurement, histological, immunohistochemical and immunofluorescence analysis.Results: We have successfully isolated GMSCs and exosomes with a mean diameter of 127 nm. The chitosan/silk hydrogel had the appropriate properties of swelling and moisture retention capacity. The in vivo studies showed that the incorporating of GMSC-derived exosomes to hydrogel could effectively promote healing of diabetic skin defects. The histological analysis revealed more neo-epithelium and collagen in the hydrogel-exosome group. In addition, the hydrogel-exosome group had the highest microvessel density and nerve density.Conclusions: The combination of GMSC-derived exosomes and hydrogel could effectively promote skin wound healing in diabetic rats by promoting the re-epithelialization, deposition and remodeling of collagen and by enhancing angiogenesis and neuronal ingrowth. These findings not only provide new information on the role of the GMSC-derived exosomes in wound healing but also provide a novel non-invasive application method of exosomes with practical value for skin repair.

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“…It has been shown that CB hematopoietic progenitors influence the expression of genes encoding for adhesion molecules and molecules of the connective tissue matrix [143]. Its remodeling enzymes was also studied in multipotent mesenchymal stromal cells (MSCs) from human adipose tissue [144]. In a direct cell-cell contact culture system, WJ-MSCs enhanced the expansion of CB-CD34+ cells [145].…”

Section: Past and Future Perspectivesmentioning

confidence: 99%

Autologous Cord Blood in Children with Cerebral Palsy: A Review

Boruczkowski

Pujal²,

Zdolińska-Malinowska

2019

IJMS

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The aim of this narrative review is to report on the current knowledge regarding the clinical use of umbilical cord blood (CB) based on articles from PubMed and clinical trials registered on ClinicalTrials.gov. An increasing amount of evidence suggests that CB may be used for both early diagnostics and treatment of cerebral palsy. The acidity of CB and its biochemical parameters, including dozens of cytokines, growth factors, and other metabolites (such as amino acids, acylcarnitines, phosphatidylcholines, succinate, glycerol, 3-hydroxybutyrate, and O-phosphocholine) are predictors of future neurodevelopment. In addition, several clinical studies confirmed the safety and efficacy of CB administration in both autologous and allogeneic models, including a meta-analysis of five clinical trials involving a total of 328 participants. Currently, nine clinical trials assessing the use of autologous umbilical CB in children diagnosed with hypoxic-ischemic encephalopathy or cerebral palsy are in progress. The total population assessed in these trials exceeds 2500 patients.

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Implications of Extracellular Matrix Production by Adipose Tissue-Derived Stem Cells for Development of Wound Healing Therapies

Cited by 75 publications

References 84 publications

Hopes and Limits of Adipose-Derived Stem Cells (ADSCs) and Mesenchymal Stem Cells (MSCs) in Wound Healing

Hopes and Limits of Adipose-Derived Stem Cells (ADSCs) and Mesenchymal Stem Cells (MSCs) in Wound Healing

GMSC-Derived Exosomes Combined with a Chitosan/Silk Hydrogel Sponge Accelerates Wound Healing in a Diabetic Rat Skin Defect Model

Autologous Cord Blood in Children with Cerebral Palsy: A Review

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