Mesenchymal Derivatives of Genetically Unstable Human Embryonic Stem Cells Are Maintained Unstable but Undergo Senescence in Culture As Do Bone Marrow–Derived Mesenchymal Stem Cells

Karagiannidou, Angeliki; Varela, Ioanna; Γιαννίκου, Κρινιώ; Tzetis, Maria; Spyropoulos, Antonia; Paterakis, George; Petrakou, Eftichia; Theodosaki, Maria; Goussetis, Evgenios; Kanavakis, Emmanuel

doi:10.1089/cell.2013.0040

Cited by 4 publications

(4 citation statements)

References 22 publications

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“…Senescent BMSCs exhibit organelle stress, shortened telomeres, impaired DNA and protein, and increased reactive oxygen species (ROS) levels. Replicative senescence and accumulation of γH2AX foci are observed with long-term culture 29 . Our results showed that the expression levels of senescence-related genes, including p16 , p21 , and p53 , were lower in infant BMSCs at both early and late passages compared with adult BMSCs.…”

Section: Discussionmentioning

confidence: 99%

Proliferation and Differentiation Potential of Bone Marrow–Derived Mesenchymal Stem Cells From Children With Polydactyly and Adults With Basal Joint Arthritis

Yeh,

Yu,

Chou

et al. 2024

Cell Transplant

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This study compared the proliferation and differentiation potential of bone marrow–derived mesenchymal stem cells (BMSCs) derived from infants with polydactyly and adults with basal joint arthritis. The proliferation rate of adult and infant BMSCs was determined by the cell number changes and doubling times. The γH2AX immunofluorescence staining, age-related gene expression, senescence-associated β-galactosidase (SA-β-gal) staining were analyzed to determine the senescence state of adult and infant BMSCs. The expression levels of superoxide dismutases (SODs) and genes associated with various types of differentiation were measured using Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR). Differentiation levels were evaluated through histochemical and immunohistochemical staining. The results showed that infant BMSCs had a significantly higher increase in cell numbers and faster doubling times compared with adult BMSCs. Infant BMSCs at late stages exhibited reduced γH2AX expression and SA-β-gal staining, indicating lower levels of senescence. The expression levels of senescence-related genes ( p16, p21, and p53) in infant BMSCs were also lower than in adult BMSCs. In addition, infant BMSCs demonstrated higher antioxidative ability with elevated expression of SOD1, SOD2, and SOD3 compared with adult BMSCs. In terms of differentiation potential, infant BMSCs outperformed adult BMSCs in chondrogenesis, as indicated by higher expression levels of chondrogenic genes ( SOX9, COL2, and COL10) and positive immunohistochemical staining. Moreover, differentiated cells derived from infant BMSCs exhibited significantly higher expression levels of osteogenic, tenogenic, hepatogenic, and neurogenic genes compared with those derived from adult BMSCs. Histochemical and immunofluorescence staining confirmed these findings. However, adult BMSCs showed lower adipogenic differentiation potential compared with infant BMSCs. Overall, infant BMSCs demonstrated superior characteristics, including higher proliferation rates, enhanced antioxidative activity, and greater differentiation potential into various lineages. They also exhibited reduced cellular senescence. These findings, within the context of cellular differentiation, suggest potential implications for the use of allogeneic BMSC transplantation, emphasizing the need for further in vivo investigation.

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Section: Discussionmentioning

confidence: 99%

Proliferation and Differentiation Potential of Bone Marrow–Derived Mesenchymal Stem Cells From Children With Polydactyly and Adults With Basal Joint Arthritis

Yeh,

Yu,

Chou

et al. 2024

Cell Transplant

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“…iPSC_OA were induced towards the mesenchymal lineage via Embryoid body (EB) formation [ 33 ]. Embryoid bodies were subsequently collected and transferred into gelatin-coated flasks in an MSC differentiation medium consisting of Knockout DMEM supplemented with 10% KSR, 1 mM L-Glutamine, 1× non-essential amino acids and 10 ng/mL bFGF.…”

Section: Methodsmentioning

confidence: 99%

Integration of Transcriptome and MicroRNA Profile Analysis of iMSCs Defines Their Rejuvenated State and Conveys Them into a Novel Resource for Cell Therapy in Osteoarthritis

Konteles

Papathanasiou

Tzetis

et al. 2023

Cells

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Although MSCs grant pronounced potential for cell therapies, several factors, such as their heterogeneity restrict their use. To overcome these limitations, iMSCs (MSCs derived from induced pluripotent stem cells (iPSCs) have attracted attention. Here, we analyzed the transcriptome of MSCs, iPSCs and iMSCs derived from healthy individuals and osteoarthritis (OA) patients and explored miRNA-mRNA interactions during these transitions. We performed RNA-seq and gene expression comparisons and Protein-Protein-Interaction analysis followed by GO enrichment and KEGG pathway analyses. MicroRNAs’ (miRNA) expression profile using miRarrays and differentially expressed miRNA’s impact on regulating iMSCs gene expression was also explored. Our analyses revealed that iMSCs derivation from iPSCs favors the expression of genes conferring high proliferation, differentiation, and migration properties, all of which contribute to a rejuvenated state of iMSCs compared to primary MSCs. Additionally, our exploration of the involvement of miRNAs in this rejuvenated iMSCs transcriptome concluded in twenty-six miRNAs that, as our analysis showed, are implicated in pluripotency. Notably, the identified here interactions between hsa-let7b/i, hsa-miR-221/222-3p, hsa-miR-302c, hsa-miR-181a, hsa-miR-331 with target genes HMGA2, IGF2BP3, STARD4, and APOL6 could prove to be the necessary tools that will convey iMSCs into the ideal mean for cell therapy in osteoarthritis.

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“…On the other hand, adipose-tissue-derived MSCs expressed low percentages of aneuploidy cells in early passages 0-4, whereas prolonged culture expansion for 5-16 passages was characterized by significantly high aneuploidy percentages without malignant transformations [58]. In addition, human embryonic stem cells maintained unstable multiple chromosomal alterations in differentiated MSCs, which enter replicative senescence after long-term culture passage [59]. Moreover, long-term in vitro expansion of MSCs showed an accumulation of γH2AX foci, a well-known marker of genomic instability whose numbers were increased in late passages with a strong increase at 16-18 passages.…”

Section: Genetic Materials Damagementioning

confidence: 99%

Aging of mesenchymal stem cell: machinery, markers, and strategies of fighting

et al. 2022

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Human mesenchymal stem cells (MSCs) are primary multipotent cells capable of differentiating into osteocytes, chondrocytes, and adipocytes when stimulated under appropriate conditions. The role of MSCs in tissue homeostasis, aging-related diseases, and cellular therapy is clinically suggested. As aging is a universal problem that has large socioeconomic effects, an improved understanding of the concepts of aging can direct public policies that reduce its adverse impacts on the healthcare system and humanity. Several studies of aging have been carried out over several years to understand the phenomenon and different factors affecting human aging. A reduced ability of adult stem cell populations to reproduce and regenerate is one of the main contributors to the human aging process. In this context, MSCs senescence is a major challenge in front of cellular therapy advancement. Many factors, ranging from genetic and metabolic pathways to extrinsic factors through various cellular signaling pathways, are involved in regulating the mechanism of MSC senescence. To better understand and reverse cellular senescence, this review highlights the underlying mechanisms and signs of MSC cellular senescence, and discusses the strategies to combat aging and cellular senescence. Graphical Abstract

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Mesenchymal Derivatives of Genetically Unstable Human Embryonic Stem Cells Are Maintained Unstable but Undergo Senescence in Culture As Do Bone Marrow–Derived Mesenchymal Stem Cells

Cited by 4 publications

References 22 publications

Proliferation and Differentiation Potential of Bone Marrow–Derived Mesenchymal Stem Cells From Children With Polydactyly and Adults With Basal Joint Arthritis

Proliferation and Differentiation Potential of Bone Marrow–Derived Mesenchymal Stem Cells From Children With Polydactyly and Adults With Basal Joint Arthritis

Integration of Transcriptome and MicroRNA Profile Analysis of iMSCs Defines Their Rejuvenated State and Conveys Them into a Novel Resource for Cell Therapy in Osteoarthritis

Aging of mesenchymal stem cell: machinery, markers, and strategies of fighting

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