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pmid:38520027

Identification of potential biomarkers for aging diagnosis of mesenchymal stem cells derived from the aged donors.

Miao Hao · Hongyu Jiang · Yuan Zhao · Chunyi Li · Jinlan Jiang

Stem cell research & therapy · 2024 doi:10.1186/s13287-024-03689-1

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Experiment

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Identification of potential biomarkers for aging diagnosis of mesenchymal stem cells derived from the aged donors.
doi
10.1186/s13287-024-03689-1
pmid
38520027
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Miao Hao
[1]
Hongyu Jiang
[2]
Yuan Zhao
[3]
Chunyi Li
[4]
Jinlan Jiang
journal
Stem cell research & therapy
year
2024
abstract
BACKGROUND: The clinical application of human bone-marrow derived mesenchymal stem cells (MSCs) for the treatment of refractory diseases has achieved remarkable results. However, there is a need for a systematic evaluation of the quality and safety of MSCs sourced from donors. In this study, we sought to assess one potential factor that might impact quality, namely the age of the donor. METHODS: We downloaded two data sets from each of two Gene Expression Omnibus (GEO), GSE39035 and GSE97311 databases, namely samples form young (< 65 years of age) and old (> 65) donor groups. Through, bioinformatics analysis and experimental validation to these retrieved data, we found that MSCs derived from aged donors can lead to differential expression of gene profiles compared with those from young donors, and potentially affect the function of MSCs, and may even induce malignant tumors. RESULTS: We identified a total of 337 differentially expressed genes (DEGs), including two upregulated and eight downregulated genes from the databases of both GSE39035 and GSE97311. We further identified 13 hub genes. Six of them, TBX15, IGF1, GATA2, PITX2, SNAI1 and VCAN, were highly expressed in many human malignancies in Human Protein Atlas database. In the MSCs in vitro senescent cell model, qPCR analysis validated that all six hub genes were highly expressed in senescent MSCs. Our findings confirm that aged donors of MSCs have a significant effect on gene expression profiles. The MSCs from old donors have the potential to cause a variety of malignancies. These TBX15, IGF1, GATA2, PITX2, SNAI1, VCAN genes could be used as potential biomarkers to diagnosis aging state of donor MSCs, and evaluate whether MSCs derived from an aged donor could be used for therapy in the clinic. Our findings provide a diagnostic basis for the clinical use of MSCs to treat a variety of diseases. CONCLUSIONS: Therefore, our findings not only provide guidance for the safe and standardized use of MSCs in the clinic for the treatment of various diseases, but also provide insights into the use of cell regeneration approaches to reverse aging and support rejuvenation.
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Using SPSS 22.0, we constructed receiver operating characteristic (ROC) curves and calculated the area under the curve (AUC) of the hub genes to compare the AUC as the index of the model.
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sections[13] "Statistics analysis" paragraph 2
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Using SPSS 22.0, we constructed receiver operating characteristic (ROC) curves and calculated the area under the curve (AUC) of the hub genes to compare the AUC as the index of the model.
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The datasets analyzed in this study are available in GEO database. GSE39035 repository at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE39035. GSE97311 repository at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE97311.
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The datasets analyzed in this study are available in GEO database. GSE39035 repository at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE39035. GSE97311 repository at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE97311.
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Receiver operating characteristic curve analysis of two public GEO microarray datasets identified TBX15, IGF1, GATA2, PITX2, SNAI1, and VCAN as potential biomarkers of MSC donor age.
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Figure 5A shows the results of GSE39035: the AUC for TBX15, IGF1, GATA2, PITX2, SNAI1, VCAN were 1.000 [95% confidence interval (Cl), 1.000–1.000; P < 0.05], 0.938 (95% Cl, 0.824-1.000; P < 0.05), 0.750 (95% Cl, 0.488-1.000; P < 0.05), 1.000 (95% Cl, 1.000–1.000; P < 0.05), 0.891 (95% Cl, 0.700-1.000; P < 0.05) and 0.984 (95% Cl, 0.941-1.000; P < 0.05).
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These results indicate that TBX15, IGF1, GATA2, PITX2 SNAI1 and VCAN may serve as potential biomarkers for evaluating the age of MSCs donors or the quality of MSCs.
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Figure 5A shows the results of GSE39035: the AUC for TBX15, IGF1, GATA2, PITX2, SNAI1, VCAN were 1.000 [95% confidence interval (Cl), 1.000–1.000; P < 0.05], 0.938 (95% Cl, 0.824-1.000; P < 0.05), 0.750 (95% Cl, 0.488-1.000; P < 0.05), 1.000 (95% Cl, 1.000–1.000; P < 0.05), 0.891 (95% Cl, 0.700-1.000; P < 0.05) and 0.984 (95% Cl, 0.941-1.000; P < 0.05).
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Figure 5B shows the AUC curve in the groups classified as young and old in the GSE97311 datasets.
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Receiver operating characteristic curve analysis of two public GEO microarray datasets identified TBX15, IGF1, GATA2, PITX2, SNAI1, and VCAN as potential biomarkers of MSC donor age.
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. In the MSCs in vitro senescent cell model, qPCR analysis validated that all six hub genes we
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Complete file
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However, there is a need for a systematic evaluation of the quality and safety of MSCs sourced from donors. In this study, we sought to assess one potential factor that might impact quality, namely the age of the donor.\nMETHODS: We downloaded two data sets from each of two Gene Expression Omnibus (GEO), GSE39035 and GSE97311 databases, namely samples form young (< 65 years of age) and old (> 65) donor groups. Through, bioinformatics analysis and experimental validation to these retrieved data, we found that MSCs derived from aged donors can lead to differential expression of gene profiles compared with those from young donors, and potentially affect the function of MSCs, and may even induce malignant tumors.\nRESULTS: We identified a total of 337 differentially expressed genes (DEGs), including two upregulated and eight downregulated genes from the databases of both GSE39035 and GSE97311. We further identified 13 hub genes. Six of them, TBX15, IGF1, GATA2, PITX2, SNAI1 and VCAN, were highly expressed in many human malignancies in Human Protein Atlas database. In the MSCs in vitro senescent cell model, qPCR analysis validated that all six hub genes were highly expressed in senescent MSCs. Our findings confirm that aged donors of MSCs have a significant effect on gene expression profiles. The MSCs from old donors have the potential to cause a variety of malignancies. These TBX15, IGF1, GATA2, PITX2, SNAI1, VCAN genes could be used as potential biomarkers to diagnosis aging state of donor MSCs, and evaluate whether MSCs derived from an aged donor could be used for therapy in the clinic. Our findings provide a diagnostic basis for the clinical use of MSCs to treat a variety of diseases.\nCONCLUSIONS: Therefore, our findings not only provide guidance for the safe and standardized use of MSCs in the clinic for the treatment of various diseases, but also provide insights into the use of cell regeneration approaches to reverse aging and support rejuvenation.", "claims": [{"id": "claim-method", "statement": "Using SPSS 22.0, we constructed receiver operating characteristic (ROC) curves and calculated the area under the curve (AUC) of the hub genes to compare the AUC as the index of the model.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38520027", "locator": "sections[13] \"Statistics analysis\" paragraph 2", "quote": "Using SPSS 22.0, we constructed receiver operating characteristic (ROC) curves and calculated the area under the curve (AUC) of the hub genes to compare the AUC as the index of the model."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analyzed in this study are available in GEO database. GSE39035 repository at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE39035. GSE97311 repository at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE97311.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38520027", "locator": "sections[28] \"Data availability\" paragraph 2", "quote": "The datasets analyzed in this study are available in GEO database. GSE39035 repository at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE39035. 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