Epigenetic biomarkers indicate islet cell death in xenotransplantation

表观遗传生物标志物表明异种移植中的胰岛细胞死亡

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作者:Christopher Faulk, Kate R Mueller, David Cheishvili, Mathia Colwell, Anne-Sophie Pepin, Moshe Syzf, Bernhard J Hering, Christopher Burlak

Aims

The present study identified a biomarker of islet death using differential methylation of the insulin gene, INS, originating from β-cells in porcine islets. Materials &

Background

Xenotransplantation of porcine islets has emerged in recent decades as a potential treatment for type 1 diabetes (T1D). Current

Conclusion

Moreover, the results of this study indicate a highly specific epigenetic biomarker, capable of detecting a single islet, supporting the measurement of cfDNA as a biomarker for transplanted islet death. Defining the epigenetic characteristics of porcine-derived islets within cfDNA will be crucial to develop a better understanding of graft survival immunology for transplantation.

Methods

Pyrosequencing primers specific for porcine INS were designed to quantify hypomethylation along 12 cysteine-guanine dinucleotide (CpG) sites, including three sites in the cyclic adenosine monophosphate (cAMP) response element (CRE) binding protein 2 (CRE2) binding region of the 5' untranslated region (UTR) and nine sites within intron 2.

Results

PCR amplification of bisulfite-converted DNA combined with pyrosequencing data support the

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