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Promising improvement in infected Wound Healing in Type two Diabetic rats by Combined effects of conditioned medium of human adipose-derived stem cells plus Photobiomodulation.

ABSTRACT:

Background

We aimed to examine the accompanying and solo impacts of conditioned medium of human adipose-derived stem cells (h-ASC-COM) and photobiomodulation (PBM) on the maturation stage of an ischemic infected delayed-healing wound model (IIDHWM) of rats with type 2 diabetes (TIIDM).

Results

Outcomes of the wound closure ratio (WCR) results, tensiometrical microbiological, and stereological assessment followed almost identical patterns. While the outcomes of h-ASC-COM + PBM, PBM only, and h-ASC-COM only regimes were significantly better for all evaluated methods than those of group 1(all, p < 0.001), PBM alone and h-ASC-COM + PBM therapy achieved superior results than h-ASC-COM only (ranged from p = 0.05 to p < 0.001). In terms of tensiometrical and stereological examinations, the results of h-ASC-COM + PBM experienced better results than the PBM only (all, p < 0.001).

Conclusions

h-ASC-COM + PBM, PBM, and h-ASC-COM cures expressively accelerated the maturation stage in the wound healing process of IIDHWM with MRSA in TIIDM rats by diminishing the inflammatory reaction, and the microbial flora of MRSA; and increasing wound strength, WCR, number of fibroblasts, and new blood vessels. While the h-ASC-COM + PBM and PBM were more suitable than the effect of h-ASC-COM, the results of h-ASC-COM + PBM were superior to PBM only.

SUBMITTER: Sohrabi K

PROVIDER: S-EPMC10648630 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

Promising improvement in infected Wound Healing in Type two Diabetic rats by Combined effects of conditioned medium of human adipose-derived stem cells plus Photobiomodulation.

Sohrabi Kaysan K Ahmadi Houssein H Amini Abdollah A Ahrabi Behnaz B Mostafavinia Atarodalsadat A Omidi Hamidreza H Mirzaei Mansooreh M Fadaei Fathabady Fatemeh F Fridoni Mohammadjavad M Rahmannia Maryam M Chien Sufan S Bayat Mohammad M

Laboratory animal research 20231115 1

<h4>Background</h4>We aimed to examine the accompanying and solo impacts of conditioned medium of human adipose-derived stem cells (h-ASC-COM) and photobiomodulation (PBM) on the maturation stage of an ischemic infected delayed-healing wound model (IIDHWM) of rats with type 2 diabetes (TIIDM).<h4>Results</h4>Outcomes of the wound closure ratio (WCR) results, tensiometrical microbiological, and stereological assessment followed almost identical patterns. While the outcomes of h-ASC-COM + PBM, PBM ...[more]

PMID: 37964303

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Project description:PurposeThis study aimed to investigate the effects of photobiomodulation (PBM) and conditioned medium (CM) derived from human adipose-derived stem cells (h-ASCs), both individually and in combination, on the maturation stage of an ischemic infected delayed healing wound model (IIDHWM) in type I diabetic (TIDM) rats.MethodsThe study involved the extraction of h-ASCs from donated fat, assessment of their immunophenotypic markers, cell culture, and extraction and concentration of CM from cultured 1 × 10^6 h-ASCs. TIDM was induced in 24 male adult rats, divided into four groups: control, CM group, PBM group (80 Hz, 0.2 J/cm2, 890 nm), and rats receiving both CM and PBM. Clinical and laboratory evaluations were conducted on days 4, 8, and 16, and euthanasia was performed using CO2 on day 16. Tensiometrical and stereological examinations were carried out using two wound samples from each rat.ResultsAcross all evaluated factors, including wound closure ratio, microbiological, tensiometrical, and stereological parameters, similar patterns were observed. The outcomes of CM + PBM, PBM, and CM treatments were significantly superior in all evaluated parameters compared to the control group (p = 0.000 for all). Both PBM and CM + PBM treatments showed better tensiometrical and stereological results than CM alone (almost all, p = 0.000), and CM + PBM outperformed PBM alone in almost all aspects (p = 0.000). Microbiologically, both CM + PBM and PBM exhibited fewer colony-forming units (CFU) than CM alone (both, p = 0.000).ConclusionPBM, CM, and CM + PBM interventions substantially enhanced the maturation stage of the wound healing process in IIDHWM of TIDM rats by mitigating the inflammatory response and reducing CFU count. Moreover, these treatments promoted new tissue formation in the wound bed and improved wound strength. Notably, the combined effects of CM + PBM surpassed the individual effects of CM and PBM.Supplementary informationThe online version contains supplementary material available at 10.1007/s40200-023-01285-3.

Project description:BackgroundWound healing represents a complex biological process, critically important in clinical practice due to its direct implication in a patient's recovery and quality of life. Conservative wound management frequently falls short in providing an ideal environment for the optimal tissue regeneration, often resulting in extended healing periods and elevated risk of infection and other complications. The emerging biomaterials, particularly hydrogels, have shown substantial promise in addressing these challenges by offering properties such as biocompatibility, biodegradability, and the ability to cure wound environment. Recent advancements have highlighted the therapeutic potential of integrating cell-derived conditioned medium (CM) into hydrogel matrices. Cell-derived CM represents a rich array of bioactive molecules, demonstrating significant efficacy in modulating cellular activities crucial for wound healing, including cellular proliferation, migration, and angiogenesis.MethodsThe methodology of this review adheres to the standards set by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. The review includes a selection of studies published within the last five years, focusing on in vivo experiments involving various types of skin injuries treated with topically applied hydrogels loaded with CM (H-CM). The search strategy refers to the PICO framework and includes the assessment of study quality by CAMARADES tool.ResultsThe systematic review represents a detailed evaluation of H-CM dressings wound healing efficiency based on the experimental results of cell-based assays and animal wound models. The study targets to reveal wound healing capacity of H-CM dressings, and provides a comparative data analysis, limitations of methods and discussions of H-CM role in advancing the wound healing therapy.ConclusionsThe data presented demonstrate that H-CM is a promising material for advanced wound healing and regenerative medicine. These dressings possess proved in vitro/in vivo efficacy that highlights their strong clinical potential and paves the way to further investigations of H-CM formulations within clinical trials.

Project description:BackgroundAging skin is characterized by a disturbed structure and lack of blood supply, which makes it difficult to heal once injured. ADSCs secrete large amounts of cytokines, which promote wound healing and vascular regeneration through paracrine secretion, and the number of cytokines can be elevated by hypoxic pretreating. However, the components of ADSCs are difficult to retain in wounds. Gelatin methacrylate (GelMA) is a photopolymerizable hydrogel synthesized from gelatin and has recently emerged as a potentially attractive material for tissue engineering applications. GelMA loaded with concentrated hypoxic pretreated ADSCs conditioned medium could provide a new method of treating wounds in aged skin.MethodsPrimary ADSCs were isolated from human adipose tissue and characterized by flow cytometry and differentiation test. ADSCs in passages 4-6 were pretreated in the hypoxic and normoxic environments to collect conditioned medium, the conditioned medium was then concentrated to prepare concentrated ADSCs conditioned medium(cADSC-CM)(the one collected from ADSCs under hypoxia was called hypo-CM ,and the one from normoxia was called nor-CM). The concentration of cytokines was detected. After treated with cADSC-CM, the abilities of proliferation, migration, and tube formation of human umbilical vascular endothelial cells (HUVECs) were assayed, and Akt/mTOR and MAPK signal pathway was detected using western blotting. GelMA+hypo-CM hydrogel was prepared, and a comprehensive evaluation of morphology, protein release efficiency, degradation rate, mechanical properties, and rheology properties were performed. Full-thickness skin wounds were created on the backs of 20-month-old mice. After surgery, GelMA, GelMA+F12, GelMA+hypo-CM, and GelMA+nor-CM were applied to the wound surface respectively. H&E, Masson, and immunohistochemistry staining were performed, and a laser Doppler perfusion imager was used to evaluate the blood perfusion. The student's t-test was used for analysis between two groups and a one-way analysis of variance (ANOVA) was used for analysis among multi groups.ResultsOur results revealed that 1) wounds in aged skin healed more slowly than that in young skin and exhibited poorer perfusion; 2) hypoxic pretreated ADSCs secreted more cytokines including VEGF by activating HIF1α; 3) hypo-CM promoted proliferation and migration of HUVECs through VEGF/Akt/mTOR and MAPK signal pathway; 4) GelMA-hypoCM accelerated wound healing and angiogenesis in aged skin in vivo.ConclusionGelMA loaded with concentrated hypoxic pretreated adipose-derived mesenchymal stem cells conditioned medium could accelerate wound healing in aged skin by promoting angiogenesis.

Project description:BackgroundStem cell therapies have been widely investigated for their healing effects. However, the translation of these therapies has been hampered by the requirement to deliver live allogeneic or autologous cells directly to the wound in a clinical setting. Multipotent adult progenitor cells (MAPC® cells) are a subpopulation of bone marrow-derived adherent stem cells that secrete a wide range of factors known to accelerate the wound healing process. The aim of this study was to determine the impact of MAPC cells secretome on healing outcomes without the presence of MAPC cells.MethodsThe effect of MAPC-conditioned medium (MAPC-CM) on the capacity of keratinocytes, fibroblasts and endothelial cells to migrate and proliferate was determined in vitro using scratch wound closure and WST1 assay, respectively. The effect of MAPC-CM on collagen deposition and angiogenesis was also assessed using in vitro methods. Additionally, two excisional wounds were created on the dorsal surface of mice (n = 8/group) and 100 μL of 20× MAPC-CM were intradermally injected to the wound margins. Wound tissues were collected at 3, 7 and 14 days post-wounding and stained with H&E for microscopic analysis. Immunohistochemistry was performed to investigate inflammation, angiogenesis and collagen deposition in the wounds.ResultsSkin fibroblasts, keratinocytes and endothelial cells treated with MAPC-CM all showed improved rates of scratch closure and increased cellular proliferation. Moreover, fibroblasts treated with MAPC-CM deposited more collagens I and III and endothelial cells treated with MAPC-CM showed increased capillary tube formation. Murine excisional wounds intradermally injected with MAPC-CM showed a significant reduction in the wound area and an increase in the rate of reepithelialisation. The results also showed that inflammatory cell infiltration was decreased while an increase in angiogenesis, as well as collagens I and III expressions, was observed.ConclusionThese findings suggest that factors produced by MAPC cells can have an important effect on cutaneous wound healing by affecting skin cell proliferation and migration, balancing inflammation and improving the formation of extracellular matrix and angiogenesis. Development of stem cell-free therapy for the treatment of wounds may be a more clinically translatable approach for improving healing outcomes.

Dataset Information

Promising improvement in infected Wound Healing in Type two Diabetic rats by Combined effects of conditioned medium of human adipose-derived stem cells plus Photobiomodulation.

Background

Results

Conclusions

Publications

Promising improvement in infected Wound Healing in Type two Diabetic rats by Combined effects of conditioned medium of human adipose-derived stem cells plus Photobiomodulation.

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