3D culture of alginate-hyaluronic acid hydrogel supports the stemness of human mesenchymal stem cells

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Feb. 23, 2024

Abstract The three-dimensional (3D) cell culture system is being employed more frequently to investigate engineering and tissue repair due its close mimicry of in vivo microenvironments. In this study, we developed natural biomaterials, including hyaluronic acid, alginate, gelatin, mimic the creation a 3D human mesenchymal stem (hMSC) extracellular environment selected hydrogels with high proliferation capacity for MSC culture. Human cells were encapsulated within hydrogels, an investigation was conducted into effects on viability proliferation, stemness properties, telomere activity compared 2D monolayer Hydrogel characterization, Live/Dead assay, gene expression, relative length, stemness-related proteins by immunofluorescence staining examined. results showed that alginate-hyaluronic acid (AL-HA) increased grown as cellular spheroids presented survival rate 77.36% during period 14 days. Furthermore, expression genes ( OCT-4 , NANOG SOX2 SIRT1 ), growth development YAP TAZ Ki67 ) after Moreover, MSCs enhanced, indicated upregulation telomerase reverse transcriptase hTERT length (T/S ratio) Altogether, these data suggest could serve promising material maintaining properties might be suitable carrier proposals.

Language: Английский

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Biomaterials for immunomodulation in wound healing

Regenerative Biomaterials, Journal Year: 2024, Volume and Issue: 11

Published: Jan. 1, 2024

Abstract The substantial economic impact of non-healing wounds, scarring, and burns stemming from skin injuries is evident, resulting in a financial burden on both patients the healthcare system. This review paper provides an overview skin’s vital role guarding against various environmental challenges as body’s largest protective organ associated developments biomaterials for wound healing. We first introduce composition tissue intricate processes healing, with special attention to crucial immunomodulation acute chronic wounds. highlights how imbalance immune response, particularly wounds underlying health conditions such diabetes immunosuppression, hinders normal healing stages. Then, this distinguishes between traditional wound-healing strategies that create optimal microenvironment recent peptide-based modulate cellular responses facilitate closure. Additionally, we highlight importance considering stages process. By integrating advanced materials engineering in-depth understanding biology, approach holds promise reshaping field management ultimately offering improved outcomes

Language: Английский

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Advancing wound healing by hydrogel-based dressings loaded with cell-conditioned medium: a systematic review

Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 17, 2024

Wound healing represents a complex biological process, critically important in clinical practice due to its direct implication patient's recovery and quality of life. Conservative wound management frequently falls short providing an ideal environment for the optimal tissue regeneration, often resulting extended periods elevated risk infection other complications. The emerging biomaterials, particularly hydrogels, have shown substantial promise addressing these challenges by offering properties such as biocompatibility, biodegradability, ability cure environment. Recent advancements highlighted therapeutic potential integrating cell-derived conditioned medium (CM) into hydrogel matrices. Cell-derived CM rich array bioactive molecules, demonstrating significant efficacy modulating cellular activities crucial healing, including proliferation, migration, angiogenesis.

Language: Английский

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Stem cell-derived small extracellular vesicles embedded into methacrylated hyaluronic acid wound dressings accelerate wound repair in a pressure model of diabetic ulcer

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: Dec. 7, 2023

Abstract Over the past years, development of innovative smart wound dressings is revolutionizing care management and research. Specifically, in treatment diabetic foot wounds, three-dimensional (3D) bioprinted patches may enable personalized medicine therapies. In present work, a methacrylated hyaluronic acid (MeHA) bioink employed to manufacture 3D printed deliver small extracellular vesicles (sEVs) obtained from human mesenchymal stem cells (MSC-sEVs). The production sEVs maximized culturing MSCs bioreactor. A series vitro analyses are carried out demonstrate influence MSC-sEVs on functions dermal fibroblasts endothelial cells, which primary functional skin repair process. Results that both cell populations able internalize exposure stimulates proliferation migration. vivo experiments well-established mouse model pressure ulcer confirm regenerative properties MSC-sEVs. MeHA patch enhances effectiveness by enabling controlled release over 7 days, improve epithelialization, angiogenesis innervation. overall findings highlight loading biomaterials represents powerful technique, can translational potential parental terms regulatory economic impact.

Language: Английский

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The Hidden Power of the Secretome: Therapeutic Potential on Wound Healing and Cell-Free Regenerative Medicine—A Systematic Review

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1926 - 1926

Published: Feb. 23, 2025

Various types of wounds represent a persistent healthcare burden that demands innovative and effective therapeutic solutions. Innovative approaches have emerged focus on skin regeneration with minimal side effects. One such method is cell-free therapy utilizes the secretome human mesenchymal stem cells (hMSCs) as promising alternative to traditional cell-based therapies, leveraging complex mixture bioactive molecules, including growth factors, cytokines, extracellular vesicles, accelerate tissue regeneration. This systematic review synthesizes findings 35 studies evaluating impact hMSC-derived secretomes wound healing, their regenerative, immunomodulatory, angiogenic The influence MSC sources (adipose tissue, bone marrow, umbilical cord) culture conditions composition efficacy in cutaneous healing process examined, highlighting potential regenerative medicine. also explores emerging preclinical clinical applications, results, enhanced fibroblast proliferation, reduced inflammation, improved matrix remodeling. In addition, advances secretome-based biomaterials, hydrogels scaffolds, which optimize delivery are discussed. Despite growing body evidence supporting safety secretomes, challenges remain regarding standardization, large-scale production, validation. highlights MSC-derived next-generation approach for

Language: Английский

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Effects of Hydrogels on Mesenchymal Stem/Stromal Cells Paracrine Activity and Extracellular Vesicles Production

Journal of Extracellular Vesicles, Journal Year: 2025, Volume and Issue: 14(3)

Published: March 1, 2025

ABSTRACT Mesenchymal stem/stromal cells (MSCs) are a valuable source of paracrine factors, as they have remarkable secretory capacity, and there is sizeable knowledge base to develop industrial clinical production protocols. Promising cell‐free approaches for tissue regeneration immunomodulation driving research towards secretome applications, among which extracellular vesicles (EVs) steadily gaining attention. However, the manufacturing application EVs limited by insufficient yields, gaps, low standardization. Facing these limitations, hydrogels represent versatile three‐dimensional (3D) culture platform that can incorporate matrix (ECM) components mimic natural stem cell environment in vitro; via niche‐mimicking properties, regulate MSCs’ morphology, adhesion, proliferation, differentiation secretion capacities. impact hydrogel's architectural, biochemical biomechanical properties on remains poorly understood, field still its infancy interdependency parameters compromises comparability studies. Therefore, this review summarizes discusses reported effects hydrogel encapsulation MSC‐EVs. Considering cell‐material interactions overall activity MSCs, we identify persistent challenges from standardization process control, outline future paths research, such synergic use bioreactors enhance MSC‐EV generation.

Language: Английский

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Hydrogels Empowered Mesenchymal Stem Cells and the Derived Exosomes for Regenerative Medicine in Age-Related Musculoskeletal Diseases

Pharmacological Research, Journal Year: 2025, Volume and Issue: unknown, P. 107618 - 107618

Published: Jan. 1, 2025

Language: Английский

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Mesenchymal Stem Cell Extracellular Vesicles from Tissue-Mimetic System Enhance Epidermal Regeneration via Formation of Migratory Cell Sheets

Tissue Engineering and Regenerative Medicine, Journal Year: 2023, Volume and Issue: 20(6), P. 993 - 1013

Published: July 29, 2023

Abstract Background The secretome of adipose-derived mesenchymal stem cells (ASCs) offers a unique approach to understanding and treating wounds, including the critical process epidermal regeneration orchestrated by keratinocytes. However, 2D culture techniques drastically alter secretory dynamics ASCs, which has led ambiguity in secreted compounds (e.g., growth factors, exosomes, reactive oxygen species) may be driving epithelialization. Methods A novel tissue-mimetic 3D hydrogel system was utilized enhance retainment more regenerative ASC phenotype highlight functional differences between 3D. Subsequently, ASC-secretome stratified molecular weight presence/absence extracellular vesicles (EVs). fractions were then evaluated assess for capacity augment specific keratinocyte activities. Results Culture ASCs within enhanced protein secretion ~ 50%, exclusively coming from > 100 kDa fraction. ability modulate epithelialization functions, migration, proliferation, differentiation, morphology, resided “> kDa” fraction, with providing greatest improvement. EV two-fold exhibited dose-dependent effects on regeneration. Notably, ASC-EVs induced morphological changes keratinocytes reminiscent native regeneration, formation cell sheets. only 3D-EVs promoted collective sheet migration an epithelial-to-mesenchymal-like transition keratinocytes, whereas 2D-EVs contained anti-migratory stimulus. Conclusion This study demonstrates how environment is influencing capabilities. Additionally, role EVs modulating revealed their translatability future clinical therapies discussed.

Language: Английский

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Tailoring the secretome composition of mesenchymal stem cells to augment specific functions of epidermal regeneration: an in vitro diabetic model

Frontiers in Medical Technology, Journal Year: 2023, Volume and Issue: 5

Published: June 12, 2023

Introduction Wound healing consists of a dynamic series events that are highly dependent on paracrine factors for proper progression through the phases wound healing. Inappropriate is associated with insufficient epidermal regeneration (i.e., re-epithelialization) wounds and subsequent propagation chronic wounds, such as diabetic ulcers, which increased patient morbidity. Recently, investigation into secretome Adipose-derived Mesenchymal Stem Cells (ASCs), have shown promise in augmenting response wounds. However, currently utilized 2D culture techniques known to drastically alter regenerative phenotype ASCs. In this study novel tissue-mimetic 3D system was means Methods The capacity ASC augment activity then evaluated after exposure ASCs “wound priming stimuli” 3D. stimuli consisted coating systems matrix proteins, collagen type I, fibronectin, fibrin. To understand potential benefit context keratinocytes (KCs) were exposed super-physiological glucose levels induce diabetic-like (idKCs). Results Relative KCs, idKC exhibited 52% 23% decline proliferation migration, respectively. Subsequently, analyses performed. conditioned media (ASC-CM) from demonstrated > 50% increase secretion proteins 2-fold secreted EVs, relative culture. Interestingly, different did not total amount protein or EVs within system. evaluation specific soluble via ELISA revealed significant differences key factors, EGF, IGF-1, FGF-2, MMP-1, TIMP-1, TGF β -1. Additionally, effect ASC-EVs idKCs functionality varied significantly, 3D-Collagen providing most activity. Discussion Together, these data support utilization enhance adaptability secretory MSC-like populations order generate tailored biologics, stimuli, applications.

Language: Английский

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Unlocking the Therapeutic Potential of Adipose-Derived Stem Cell Secretome in Oral and Maxillofacial Medicine: A Composition-Based Perspective

Biology, Journal Year: 2024, Volume and Issue: 13(12), P. 1016 - 1016

Published: Dec. 5, 2024

The adipose-derived stem cell (ADSC) secretome is widely studied for its immunomodulatory and regenerative properties, yet potential in maxillofacial medicine remains largely underexplored. This review takes a composition-driven approach, beginning with list of chemokines, cytokines, receptors, inflammatory growth factors quantified the ADSC to infer applications this medical field. First, literature confirmed presence 107 bioactive ADSCs or other types mesenchymal cells. was then analyzed using Search Tool Retrieval Interacting Genes/Proteins (STRING) software, revealing 844 enriched biological processes. From these, key processes were categorized into three major clinical application areas: immunoregulation (73 factors), bone regeneration (13 wound healing soft tissue (27 several relevant more than one area. most molecules discussed context existing explore their therapeutic based on available evidence. Among TGFB1, IL10, CSF2 have been shown modulate immune responses, while OPG, IL6, HGF, TIMP1 contribute repair. Although holds great promise oral medicine, further research needed optimize validate efficacy.

Language: Английский

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