The issue of heterogeneity of MSC-based advanced therapy medicinal products–a review

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: July 26, 2024

Mesenchymal stromal stem cells (MSCs) possess a remarkable potential for numerous clinical applications due to their unique properties including self-renewal, immunomodulation, paracrine actions and multilineage differentiation. However, the translation of MSC-based Advanced Therapy Medicinal Products (ATMPs) into clinic has frequently met with inconsistent outcomes. One suspected reasons this issue is inherent extensive variability that exists among such ATMPs, which makes interpretation efficacy difficult assess, as well compare results various studies. This stems from differences in tissue sources, donor attributes, variances manufacturing protocols, modes administration. MSCs can be isolated tissues bone marrow, umbilical cord, adipose others, each its phenotypic functional characteristics. While different sources do share common features, they also exhibit distinct gene expression profiles properites. Donor-specific factors age, sex, body mass index, underlying health conditions influence MSC phenotype, morphology, differentiation function. Moreover, variations preparation products introduces additional heterogeneity result cell culture media composition, presence or absence added growth factors, use serum supplements culturing techniques. Once are formulated, storage protocols play pivotal role efficacy. Factors affect viability include concentration, delivery solution importantly, post-thawing where applicable. Ensuing, administration critically distribution functionallity administered cells. As therapies continue advance through trials, implication strategies reduce product imperative. Central addressing these challenges need precise prediction responses, require well-defined populations harmonized assessment specific functions. By issues by meaningful approaches, as, e.g., pooling, field overcome barriers towards more consistent effective therapies.

Language: Английский

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3D Cell Models in Radiobiology: Improving the Predictive Value of In Vitro Research

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 10620 - 10620

Published: June 25, 2023

Cancer is intrinsically complex, comprising both heterogeneous cellular composition and extracellular matrix. In vitro cancer research models have been widely used in the past to model study cancer. Although two-dimensional (2D) cell culture traditionally for research, they many limitations, such as disturbance of interactions between environments changes morphology, polarity, division mechanism, differentiation motion. Moreover, 2D are usually monotypic. This implies that tumor ineffective at accurately recapitulating complex aspects growth, well their radiation responses. Over decade there has significant uptake three-dimensional (3D) by researchers, highlighting a complementary studies effects on tumors, especially conjunction with chemotherapy. The introduction 3D approaches aims vivo tissue positioning itself halfway animal models, thus opening up new possibilities response mechanisms healthy tissues.

Language: Английский

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Stem Cell-Derived Extracellular Vesicles: Promising Therapeutic Opportunities for Diabetic Wound Healing

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 4357 - 4375

Published: May 1, 2024

Abstract: Wound healing is a sophisticated and orderly process of cellular interactions in which the body restores tissue architecture functionality following injury. Healing chronic diabetic wounds difficult due to impaired blood circulation, reduced immune response, disrupted repair mechanisms, are often associated with diabetes. Stem cell-derived extracellular vesicles (SC-EVs) hold regenerative potential, encapsulating diverse cargo proteins, RNAs, cytokines, presenting safe, bioactivity, less ethical issues than other treatments. SC-EVs orchestrate multiple processes by modulating communication, increasing angiogenesis, promoting recruitment differentiation progenitor cells, thereby potentiating reparative milieu for wound healing. Therefore, this review investigated effects mechanisms EVs from various stem cells healing, as well their limitations challenges. Continued exploration has potential revolutionize care. Keywords: diabetes, EVs, ncRNAs, regeneration

Language: Английский

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3D spheroid culturing of Astyanax mexicanus liver‐derived cell lines recapitulates distinct transcriptomic and metabolic states of in vivo tissue environment

Journal of Experimental Zoology Part B Molecular and Developmental Evolution, Journal Year: 2024, Volume and Issue: 342(3), P. 301 - 312

Published: Jan. 8, 2024

Abstract In vitro assays are crucial tools for gaining detailed insights into various biological processes, including metabolism. Cave morphs of the river‐dwelling fish species, Astyanax mexicanus , have adapted their metabolism allowing them to thrive in biodiversity‐deprived and nutrient‐limited environment caves. Liver‐derived cells from cave river A. proven be excellent resources better understand unique these fish. However, current 2D cultures not fully captured complex metabolic profile liver. It is known that 3D culturing can modulate transcriptomic state when compared its monolayer culture. Therefore, broaden possibilities system by modeling a wider gamut pathways, we cultured liver‐derived both surface cavefish spheroids. We successfully established at cell seeding densities several weeks characterized resultant variations. found exhibit an altered consequently represent range cycle changes antioxidant activities, associated with liver functioning as Enzymatic assay measuring antioxidants culture spheroids also revealed enhanced antioxidative capacity spheroids, line differential gene expression data. Additionally, exhibited cave‐specific signatures, making it suitable evolutionary studies adaptation. Notably, derived enriched genes responding xenobiotic stimulus, while ones immune response, which resonated physiologically adaptations each morph. Taken together, prove promising model widening our understanding vertebrates general.

Language: Английский

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Cell-Derived Matrix: Production, Decellularization, and Application of Wound Repair

Stem Cells International, Journal Year: 2024, Volume and Issue: 2024(1)

Published: Jan. 1, 2024

Chronic nonhealing wounds significantly reduce patients' quality of life and are a major burden on healthcare systems. Over the past few decades, tissue engineering materials have emerged as viable option for wound healing, with cell-derived extracellular matrix (CDM) showing remarkable results. The CDM's compatibility resemblance to natural microenvironment confer distinct advantages tissue-engineered scaffolds in repair. This review summarizes current processes CDM preparation, various cell decellularization protocols, common characterization methods. Furthermore, it discusses applications including skin defect repair, angiogenesis, engineered vessels, offers perspectives future developments.

Language: Английский

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Acceleration of burn wound healing by micronized amniotic membrane seeded with umbilical cord-derived mesenchymal stem cells

Materials Today Bio, Journal Year: 2023, Volume and Issue: 20, P. 100686 - 100686

Published: June 1, 2023

Umbilical cord-derived mesenchymal stem cells (UC-MSC) are promising candidates for wound healing. However, the low amplification efficiency of MSC in vitro and their survival rates after transplantation have limited medical application. In this study, we fabricated a micronized amniotic membrane (mAM) as microcarrier to amplify used mAM (mAM-MSC) complexes repair burn wounds. Results showed that could live proliferate on 3D culture system, exhibiting higher cell activity than 2D culture. Transcriptome sequencing expression growth factor-related, angiogenesis-related, healing-related genes was significantly upregulated mAM-MSC compared traditional 2D-cultured MSC, which verified via RT-qPCR. Gene ontology (GO) analysis differentially expressed (DEGs) significant enrichment terms related proliferation, angiogenesis, cytokine activity, healing mAM-MSC. model C57BL/6J mice, topical application accelerated injection alone accompanied by longer greater neovascularization wound.

Language: Английский

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3D pancreatic ductal adenocarcinoma desmoplastic model: Glycolysis facilitating stemness via ITGAV-PI3K-AKT-YAP1

Biomaterials Advances, Journal Year: 2025, Volume and Issue: 170, P. 214215 - 214215

Published: Jan. 29, 2025

Language: Английский

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Bioproduction Cell Lines 3d Bioprinting

Published: Jan. 1, 2025

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Investigating Connectivity Deficits in Alzheimer’s Disease Using a Novel 3D Bioprinted Model Designed to Quantify Neurite Outgrowth

Bioengineering, Journal Year: 2025, Volume and Issue: 12(3), P. 245 - 245

Published: Feb. 28, 2025

Here, we present a novel 3D bioprinted model of the forebrain cortex designed to quantify neurite outgrowth across hydrogel bridge. To validate this model, cultured Alzheimer’s disease (AD) cortical populations derived from human iPSCs carrying APP (amyloid precursor protein) mutations (K670M/N671L + V717F). Neurite and synapse formation were significantly impaired in AD mutant cultures compared controls, but was not replicated 2D, highlighting deficits these traditional 2D cell culture models. investigate mechanisms underlying models AD, assessed amyloid-β dysfunction, mitochondrial health, oxidative stress both conditions. In exhibited reduced membrane potential fragmented networks, indicating dysfunction cellular energy deficits. Additionally, elevated proteostasis disruption identified as indicators damage, which may be limiting extension. Furthermore, transcriptomic (bulk RNA-Seq) analysis revealed distinct differences gene expression pathways between suggesting alternate pathology This study demonstrates functionality for quantifying connectivity identifying mechanisms.

Language: Английский

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Unraveling the impact of human cerebrospinal fluid on human neural stem cell fate

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: March 13, 2025

Human neural stem/progenitor cells (hNSCs) can potentially treat neurological diseases, but their low survival and proliferation rates after transplantation remain challenging. In our study, we preincubated hNSCs with the human cerebrospinal fluid (CSF) to obtain closer physiological brain environment assess NSC fate therapeutic abilities in vitro, ex vivo, vivo. We observed significant changes differentiation, migratory, secretory potential of CSF-treated hNSCs, as well elevated neuroprotective co-culture ischemically damaged by oxygen-glucose deprivation (OGD) organotypic rat hippocampal slices culture (OHC) comparison cultured standard conditions. Next, investigated anti-inflammatory an vivo ouabain-induced stroke model. This study highlighted confirmed critical importance nutritional supplementation maintaining enhancing its properties.

Language: Английский

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