Modulated mesenchymal stromal cells improve skin wound healing

Liubavičiūtė, Aušra; Ivaškienė, Tatjana; Biziulevičienė, Gene

doi:10.1016/j.biologicals.2020.08.003

Cited by 7 publications

(4 citation statements)

References 85 publications

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“…Bone marrow is an important compartment of bone regulating its homeostasis. Bone marrow itself can be considered as an immune organ containing distinct cell types, which secrete a large number of cytokines and growth factors that can have angiogenic, anti-inflammatory, anti-apoptotic and immunomodulatory effects [ 121 , 122 ]. Moreover, bone marrow is a metabolic organ and has been demonstrated to regulate whole-body energy metabolism.…”

Section: Application Of Stem Cells In Skin Substitutesmentioning

confidence: 99%

Immunomodulation of Skin Repair: Cell-Based Therapeutic Strategies for Skin Replacement (A Comprehensive Review)

et al. 2022

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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.

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Section: Application Of Stem Cells In Skin Substitutesmentioning

confidence: 99%

Immunomodulation of Skin Repair: Cell-Based Therapeutic Strategies for Skin Replacement (A Comprehensive Review)

et al. 2022

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“…The clear differences between the scar formation in the saline treated wounds and regeneration of normal skin structure without scar formation in α-gal nanoparticles treated wounds, strongly suggest that the accelerated healing of these wounds also involves the recruitment of skin or mesenchymal stem cells by the localized activation of the complement cascade and the rapid recruitment of macrophages that are activated within the treated wounds. In addition to secretion of cytokines that accelerate the regeneration of the epidermis for covering the wound, these activated macrophages secrete VEGF that induce rapid vascularization of the wound [ 51 , 52 , 78 ]. The recruited macrophages were further found to display activation of fibroblast growth factor (FGF), interleukin 1 (IL1), platelet derived growth factor (PDGF), and colony stimulating factor (CSF) genes [ 51 ].…”

Section: Regeneration Of Skin Wounds By α-Gal Nanoparticles Prevents ...mentioning

confidence: 99%

“…The absence of scar tissue in the treated wounds also suggests that the regenerative processes activated by the α-gal nanoparticles treatment are initiated prior to the activation of the default fibrosis processes, thereby avoiding the mechanisms involved in scar formation. It remains to be determined whether this conducive microenvironment is more effective in enabling the endogenous recruited stem cells to proliferate and differentiate into skin cells than direct exogenous application of stem cells to wounds [ 78 ]. In addition, it may be possible that the continuous contribution of the activated macrophages in production of localized pro-reparative cytokines/growth factors may result in more effective healing and regeneration processes than exogenous cytokines administered to wounds [ 79 ].…”

Section: Regeneration Of Skin Wounds By α-Gal Nanoparticles Prevents ...mentioning

confidence: 99%

α-Gal Nanoparticles Mediated Homing of Endogenous Stem Cells for Repair and Regeneration of External and Internal Injuries by Localized Complement Activation and Macrophage Recruitment

Galili¹,

Goldufsky²,

Schaer³

2022

IJMS

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This review discusses a novel experimental approach for the regeneration of original tissue structure by recruitment of endogenous stem-cells to injured sites following administration of α-gal nanoparticles, which harness the natural anti-Gal antibody. Anti-Gal is produced in large amounts in all humans, and it binds the multiple α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R) presented on α-gal nanoparticles. In situ binding of anti-Gal to α-gal nanoparticles activates the complement system and generates complement cleavage chemotactic-peptides that rapidly recruit macrophages. Macrophages reaching anti-Gal coated α-gal nanoparticles bind them via Fc/Fc receptor interaction and polarize into M2 pro-reparative macrophages. These macrophages secrete various cytokines that orchestrate regeneration of the injured tissue, including VEGF inducing neo-vascularization and cytokines directing homing of stem-cells to injury sites. Homing of stem-cells is also directed by interaction of complement cleavage peptides with their corresponding receptors on the stem-cells. Application of α-gal nanoparticles to skin wounds of anti-Gal producing mice results in decrease in healing time by half. Furthermore, α-gal nanoparticles treated wounds restore the normal structure of the injured skin without fibrosis or scar formation. Similarly, in a mouse model of occlusion/reperfusion myocardial-infarction, near complete regeneration after intramyocardial injection of α-gal nanoparticles was demonstrated, whereas hearts injected with saline display ~20% fibrosis and scar formation of the left ventricular wall. It is suggested that recruitment of stem-cells following anti-Gal/α-gal nanoparticles interaction in injured tissues may result in induction of localized regeneration facilitated by conducive microenvironments generated by pro-reparative macrophage secretions and “cues” provided by the extracellular matrix in the injury site.

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“…Recent studies have shown that MSCs located at perivascular sites were transformed from pericytes. MSCs could rapidly respond to tissue damage, playing a role in the secretion of biological factors and immunomodulation, and promoted tissue repair synergistically with the immune systems [11][12][13]. MSCs transplantation has been extensively researched for tissue repair.…”

Section: Introductionmentioning

confidence: 99%

Human amniotic mesenchymal stem cells combined with PPCNg facilitate injured endometrial regeneration

Huang

Zhang

et al. 2022

Stem Cell Res Ther

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Background Caused by the injury to the endometrial basal layer, intrauterine adhesions (IUA) are characterized by uterine cavity obliteration, leading to impaired fertility. Human amniotic mesenchymal stem cells (hAMSCs) have the potential to promote endometrial regeneration mainly through paracrine ability. PPCNg is a thermoresponsive biomaterial consisted of Poly (polyethylene glycol citrate-co-N-isopropylacrylamide) (PPCN) mixed with gelatin, which has been reported as a scaffold for stem cell transplantation. This study aims to investigate the therapeutic effect of hAMSCs combined with PPCNg transplantation in promoting the regeneration of injured endometrium. Methods hAMSCs were cultured in different concentrates of PPCNg in vitro, and their proliferation, apoptosis and cell cycle were examined by CCK-8 assay and flow cytometry. Immunofluorescence was used to determine the MSCs specific surface markers. The expression of pluripotent genes was analyzed by qRT-PCR. The multiple-lineage differentiation potential was further evaluated by detecting the differentiation-related genes using qRT-PCR and specific staining. The Sprague–Dawley (SD) rat IUA model was established with 95% ethanol. hAMSCs combined with PPCNg were transplanted through intrauterine injection. The retention of DiR-labeled hAMSCs was observed by vivo fluorescence imaging. The endometrium morphology was assessed using hematoxylin and eosin (H&E) and Masson staining. Immunohistochemistry staining was performed to detect biomarkers related to endometrial proliferation, re-epithelialization, angiogenesis and endometrial receptivity. The function of regenerated endometrium was evaluated by pregnancy tests. Results hAMSCs maintained normal cell proliferation, apoptosis and cell cycle in PPCNg. Immunofluorescence and qRT-PCR showed that hAMSCs cultured in PPCNg and hAMSCs cultured alone expressed the same surface markers and pluripotent genes. hAMSCs exhibited normal multilineage differentiation potential in PPCNg. Vivo fluorescence imaging results revealed that the fluorescence intensity of hAMSCs combined with PPCNg intrauterine transplantation was stronger than that of direct hAMSCs intrauterine transplantation. Histological assays showed the increase in the thickness of endometrial and the number of endometrial glands, and the remarkably decrease in the fibrosis area in the PPCNg/hAMSCs group. The expressions of Ki-67, CK7, CK19, VEGF, ER and PR were significantly increased in the PPCNg/hAMSCs group. Moreover, the number of implanted embryos and pregnancy rate were significantly higher in the PPCNg/hAMSCs group than in the hAMSCs group. Conclusions PPCNg is suitable for growth, phenotype maintenance and multilineage differentiation of hAMSCs. hAMSCs combined with PPCNg intrauterine transplantation can facilitate the regeneration of injured endometrium by improving utilization rates of hAMSCs, and eventually restore reproductive capacity.

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Modulated mesenchymal stromal cells improve skin wound healing

Cited by 7 publications

References 85 publications

Immunomodulation of Skin Repair: Cell-Based Therapeutic Strategies for Skin Replacement (A Comprehensive Review)

Immunomodulation of Skin Repair: Cell-Based Therapeutic Strategies for Skin Replacement (A Comprehensive Review)

α-Gal Nanoparticles Mediated Homing of Endogenous Stem Cells for Repair and Regeneration of External and Internal Injuries by Localized Complement Activation and Macrophage Recruitment

Human amniotic mesenchymal stem cells combined with PPCNg facilitate injured endometrial regeneration

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