IL-10 Gene-Modified Human Amniotic Mesenchymal Stem Cells Augment Regenerative Wound Healing by Multiple Synergistic Effects

Xiao, Shune; Huang, Guangtao; Wei, Zairong; Nie, Kaiyu; Liu, Zhiyuan; Deng, Chao; Wang, Dali

doi:10.1155/2019/9158016

Cited by 25 publications

(27 citation statements)

References 30 publications

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“…IL-10 is a cytokine involved in the restoration of tissues via the regulation of in ammatory responses, extracellular matrix production, broblast functions, and angiogenesis [83,84]. Studies have shown that IFN-γ is a key player in activating the immunomodulatory function of murine and human MSCs through the production of several factors, including HGF and IL-10, which is consistent with the results of our study [85,86].…”

Section: Discussionsupporting

confidence: 90%

3D-printed Nerve Guidance Conduits Multi-functionalized with Canine Multipotent Mesenchymal Stromal Cells Promote Neuroregeneration after Sciatic Nerve Injury in Rats

Rodríguez-Sánchez

Pinto

Cartarozzi

et al. 2020

Preprint

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Background: Nerve injuries are debilitating, leading to long-term motor deficits. Remyelination and axonal growth are supported and enhanced by growth factor and cytokines. Combination of nerve guidance conduits (NGCs) with adipose-tissue-derived multipotent mesenchymal stromal cells (AdMSCs) has been performing promising strategy for nerve regeneration.Methods: 3D-printed polycaprolactone (PCL)-NGCs were fabricated. Wistar rats subjected to critical sciatic nerve damage (12-mm gap) were divided into sham, autograft, PCL (empty NGC), and PCL+MSC (NGC multi-functionalized with 106 canine AdMSC embedded in heterologous fibrin biopolymer) groups. In vitro, the cells were characterized and directly stimulated with interferon-gamma to evaluate their neuroregeneration potential. In vivo, the sciatic and tibial functional indices were evaluated for 12 weeks. Gait analysis and nerve conduction velocity were analyzed after 8 and 12 weeks. Morphometric analysis was performed after 8 and 12 weeks following lesion development. Real-time PCR was performed to evaluate the neurotrophic factors BDNF, GDNF, and HGF, and the cytokines IL-6 and IL-10. Immunohistochemical analysis for the p75NTR neurotrophic receptor, S100, and neurofilament was performed with the sciatic nerve.Results: The inflammatory environment in vitro have increased the expression of neurotrophins BDNF, GDNF, HGF, and IL-10 in canine AdMSCs. Nerve guidance conduits multi-functionalized with canine AdMSCs embedded in HFB improved functional motor and electrophysiological recovery compared with PCL group after 12 weeks. However, the results were not significantly different than those obtained using autografts. These findings were associated with a shift in the regeneration process towards the formation of myelinated fibers. Increased immunostaining of BDNF, GDNF, and growth factor receptor p75NTR was associated with the upregulation of BDNF, GDNF, and HGF in the spinal cord of the PCL+MSC group. A trend demonstrating higher reactivity of Schwann cells and axonal branching in the sciatic nerve was observed, and canine AdMSCs were engrafted at 30 days following repair.Conclusions: 3D-printed NGCs multi-functionalized with canine AdMSCs embedded in heterologous fibrin biopolymer as cell scaffold exerted neuroregenerative effects. Our multimodal approach, support the trophic microenvironment, resulting in a pro-regenerative state after critical sciatic nerve injury in rats.

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Section: Discussionsupporting

confidence: 90%

3D-printed Nerve Guidance Conduits Multi-functionalized with Canine Multipotent Mesenchymal Stromal Cells Promote Neuroregeneration after Sciatic Nerve Injury in Rats

Rodríguez-Sánchez

Pinto

Cartarozzi

et al. 2020

Preprint

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“…We analyze the cytokine production of the pro-inflammatory chemokine IL-8 and IL-10 and TGF-β three isoforms in SCAPs. IL-10 is an important anti-inflammatory cytokine that plays a vital role in periodontal diseases, alters bone formation ( Zhang et al., 2014 ), and is able to regulate endothelial progenitor cell development in wound healing processes ( Xiao et al., 2019 ). IL-8 is an important chemokine of interest in periodontal diseases ( Finoti et al., 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Cytokine Secretion, Viability, and Real-Time Proliferation of Apical-Papilla Stem Cells Upon Exposure to Oral Bacteria

Rakhimova

Schmidt

Landström

et al. 2021

Front. Cell. Infect. Microbiol.

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The use of stem cells from the apical papilla (SCAPs) has been proposed as a means of promoting root maturation in permanent immature teeth, and plays a significant role in regenerative dental procedures. However, the role of SCAPs may be compromised by microenvironmental factors, such as hypoxic conditions and the presence of bacteria from infected dental root canals. We aim to investigate oral bacterial modulation of SCAP in terms of binding capacity using flow cytometry and imaging, real-time cell proliferation monitoring, and cytokine secretion (IL-6, IL-8, and TGF-β isoforms) under anaerobic conditions. SCAPs were exposed to key species in dental root canal infection, namely Actinomyces gerensceriae, Slackia exigua, Fusobacterium nucleatum, and Enterococcus faecalis, as well as two probiotic strains, Lactobacillus gasseri strain B6 and Lactobacillus reuteri (DSM 17938). We found that A. gerensceriae, S. exigua, F. nucleatum, and E. faecalis, but not the Lactobacillus probiotic strains bind to SCAPs on anaerobic conditions. Enterococcus faecalis and F. nucleatum exhibited the strongest binding capacity, resulting in significantly reduced SCAP proliferation. Notably, F. nucleatum, but not E. faecalis, induce production of the proinflammatory chemokine IL-8 and IL-10 from SCAPs. Production of TGF-β1 and TGF-β2 by SCAPs was dependent on species, cell line, and time, but secretion of TGF-β3 did not vary significantly over time. In conclusion, SCAP response is compromised when exposed to bacterial stimuli from infected dental root canals in anaerobic conditions. Thus, stem cell-mediated endodontic regenerative studies need to include microenvironmental conditions, such as the presence of microorganisms to promote further advantage in the field.

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“…In this study, we analyzed the gene expression of IL10, MMP-2, GM-CSFF, and VEGFA in the process of cutaneous wound healing in a canine model treated with allogeneic ASCs. These gene products have important biological effects on wound healing [23,73].…”

Section: Discussionmentioning

confidence: 99%

“…However, for IL-10 and MMP-2 genes, there were no significant differences between treatments and between them; a possible explanation is that IL-10 regulates MMP-2 expression [73,78].…”

Section: Discussionmentioning

confidence: 99%

Cutaneous wound healing: canine allogeneic ASC therapy

et al. 2020

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Background: Wound healing is a complex biological process comprised of a series of sequential events aiming to repair injured tissue. Adult mesenchymal stem cells (MSCs) have been used in cellular therapy in preclinical animal studies; a promising source of MSCs is adipose tissue (AT). In this paper, we evaluated the clinical value and safety of the application of cultured allogenic MSCs from AT for acute and chronic skin wound healing in a canine model. Methods: Twenty-four dogs of different breeds between 1 and 10 years of age with acute and chronic wounds were studied. Morphology of the wounded skin was monitored for changes over time via serial photographs and histopathological studies. Results: The percentage of the wounds that exhibited contraction and re-epithelialization were significantly different between wounds treated with adipose mesenchymal stem cells (ASCs) and control wounds; this effect was observed in both acute and chronic conditions. At 90 days, re-epithelization of acute and chronic wounds reached more than 97%. Histopathological study revealed a reduction in inflammatory infiltrate and the presence of multiple hair follicles on day 7 after treatment with ASCs, promoting epidermal and dermal regeneration. To guarantee the safety of our treatment, we determined the serum levels of cytokine markers in our patients. ASC treatment upregulated granulocyte-macrophage colony stimulating factor (GM-CSF) at the gene level, which may contribute to the recruitment of cells that participate in skin repair to the site of injury. Conclusions: The development of an allogenic ASC therapy to improve wound healing in a canine model could have a clinical impact in human treatment.

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IL-10 Gene-Modified Human Amniotic Mesenchymal Stem Cells Augment Regenerative Wound Healing by Multiple Synergistic Effects

Cited by 25 publications

References 30 publications

3D-printed Nerve Guidance Conduits Multi-functionalized with Canine Multipotent Mesenchymal Stromal Cells Promote Neuroregeneration after Sciatic Nerve Injury in Rats

3D-printed Nerve Guidance Conduits Multi-functionalized with Canine Multipotent Mesenchymal Stromal Cells Promote Neuroregeneration after Sciatic Nerve Injury in Rats

Cytokine Secretion, Viability, and Real-Time Proliferation of Apical-Papilla Stem Cells Upon Exposure to Oral Bacteria

Cutaneous wound healing: canine allogeneic ASC therapy

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