MiR‐375 and miR‐200c as predictive biomarkers of islet isolation and transplantation in total pancreatectomy with islet autotransplantation

Yoshimatsu, Gumpei; Takita, Morihito; Kanak, Mazhar A.; Haque, Waqas; Chang, Charles; Saravanan, Prathab Balaji; Lawrence, Michael C.; Levy, Marlon F.; Naziruddin, Bashoo

doi:10.1002/jhbp.377

Cited by 21 publications

(19 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, we reported that miR-375 and miR-200c are solid biomarkers to anticipate pretransplantation and posttransplantation graft function in TPIAT patients. 14,15 MiR-375 is highly expressed in the islets and is found at a quantity of about 5.66 × 10 −2 fmol per human IEQ. In addition, it regulates glucose-mediated insulin secretion in the islets by targeting the exocytosis-related myotrophin protein producing gene MTPN.…”

Section: Discussionmentioning

confidence: 99%

“…14 Furthermore, recently, we reported that miR-375 and miR-200c are biomarkers that predict posttransplantation graft function in patients with TPIAT. 15 In the current study, we measured the absolute amount of miR-375, miR-200c, and C-peptide released during multiple stages of the islet isolation process, such as organ transportation, enzyme perfusion, pancreas digestion, islet purification, tissue recombination, and islet bagging, in 12 TPIAT cases. The quantified miRNA information was then correlated with the corresponding TPIAT recipient's posttransplantation endocrine graft function parameters-C-peptide level, SUITO index, glycated hemoglobin, and exogenous insulin requirement-for validation of the biomarkers as a way to monitor islet damage during clinical islet isolations.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Islet damage during isolation as assessed by miRNAs and the correlation of miRNA levels with posttransplantation outcome in islet autotransplantation

Saravanan

Kanak

Chang

et al. 2018

American Journal of Transplantation

Self Cite

View full text Add to dashboard Cite

High-quality pancreatic islets are essential for better posttransplantation endocrine function in total pancreatectomy with islet autotransplantation (TPIAT), yet stress during the isolation process affects quality and yield. We analyzed islet-enriched microRNAs (miRNAs) -375 and -200c released during isolation to assess damage and correlated the data with posttransplantation endocrine function. The absolute concentration of miR-375, miR-200c, and C-peptide was measured in various islet isolation steps, including digestion, dilution, recombination, purification, and bagging, in 12 cases of TPIAT. Posttransplantation glycemic control was monitored through C-peptide, hemoglobin A , insulin requirement, and SUITO index. The amount of miR-375 released was significantly higher during enzymatic digestion followed by the islet bagging (P < .001). Mir-200c mirrored these changes, albeit at lower concentrations. In contrast, the C-peptide amount was significantly higher in the purification and bagging steps (P < .001). Lower amounts of miR-375 were associated with a lower 6-month insulin requirement (P = .01) and lower hemoglobin A (P = .04). Measurement of the absolute quantity of miRNA-375 and -200c released during islet isolation is a useful tool to assess islet damage. The quantity of released miRNA is indicative of posttransplantation endocrine function in TPIAT patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Islet damage during isolation as assessed by miRNAs and the correlation of miRNA levels with posttransplantation outcome in islet autotransplantation

Saravanan

Kanak

Chang

et al. 2018

American Journal of Transplantation

Self Cite

View full text Add to dashboard Cite

show abstract

“…Another study, found a detrimental effect of fibrosis and acinar atrophy in the pancreas on islet yield . Preliminary reports suggested that islet oxygen consumption rate (OCR) , islet size index , and finally miR‐375 and miR‐200c could have some predictive values as well.…”

Section: Discussionmentioning

confidence: 97%

Assessment of simple indices based on a single fasting blood sample as a tool to estimate beta-cell function after total pancreatectomy with islet autotransplantation - a prospective study

et al. 2018

View full text Add to dashboard Cite

Summary We investigated six indices based on a single fasting blood sample for evaluation of the beta‐cell function after total pancreatectomy with islet autotransplantation (TP‐IAT). The Secretory Unit of Islet Transplant Objects (SUITO), transplant estimated function (TEF), homeostasis model assessment (HOMA‐2B%), C‐peptide/glucose ratio (CP/G), C‐peptide/glucose creatinine ratio (CP/GCr) and BETA‐2 score were compared against a 90‐min serum glucose level, weighted mean C‐peptide in mixed meal tolerance test (MMTT), beta score and the Igls score adjusted for islet function in the setting of IAT. We analyzed values from 32 MMTTs in 15 patients after TP‐IAT with a follow‐up of up to 3 years. Four (27%) individuals had discontinued insulin completely prior to day 75, while 6 out of 12 patients (50%) did not require insulin support at 1‐year follow‐up with HbA1c 6.0% (5.5–6.8). BETA‐2 was the most consistent among indices strongly correlating with all reference measures of beta‐cell function (r = 0.62–0.68). In addition, it identified insulin independence (cut‐off = 16.2) and optimal/good versus marginal islet function in the Igls score well, with AUROC of 0.85 and 0.96, respectively. Based on a single fasting blood sample, BETA‐2 score has the most reliable discriminant value for the assessment of graft function in patients undergoing TP‐IAT.

show abstract

“…Following up a total pancreatectomy with islet autotransplantation (TPIAT) patients for 1-year post-transplantation ( n = 31) revealed that miR-200c correlates with the islet metabolic transplantation outcomes. The data showed that high relative miR-200c expression (< 1.5) was associated with a favourable engraftment function and with less insulin dependence [ 66 ]. These early observations need to be followed up with large longitudinal studies.…”

Section: Microrna In Assessing the Outcomes Of Clinical Islet Transplmentioning

confidence: 99%

“… miR-200c could be a novel biomarker for predicting metabolic graft function post the TPIAT procedure. [ 66 ] Unmethylated INS DNA a CpG -206 & CpG-135 Plasma and whole Blood samples 41–53 Day 1 and day 14 Nested methylation-specific PCR Whole blood samples: The level of unmethylated INS rose significantly 1-day post the graft; the signal remained elevated 14 days post the graft. Plasma samples: The level of unmethylated INS was significantly elevated 1-day post the graft, and fell by the 14th day after the graft.…”

Section: Dna Methylation In Assessing the Outcomes Of Clinical Islet mentioning

confidence: 99%

Biomarkers in Islet Cell Transplantation for Type 1 Diabetes

AlRashidi

Gillespie

2018

Curr Diab Rep

View full text Add to dashboard Cite

Purpose of ReviewIslet transplantation, an important approach to achieve insulin independence for individuals with type 1 diabetes, is limited by the lack of accurate biomarkers to track beta-cell death post islet infusion. In this review, we will discuss existing and recently described biomarkers.Recent FindingsAs beta cells are killed by the immune system, fragments of beta cell-specific cell-free DNA and proteins are released into the periphery. Several different strategies to identify these fragments have been described. Some circulating, non-coding microRNAs, particularly miRNA-375 are also showing potential to reflect the rate of beta cell loss post-clinical islet transplantation.SummaryRecent advances in identifying accurate beta cell-specific biomarkers such as differentially methylated insulin cell-free DNA and circulating miRNA-375 may help predict clinical outcomes. More studies are required to examine the robustness of these biomarkers to detect chronic beta-cell loss in islet transplantation recipients.

show abstract

MiR‐375 and miR‐200c as predictive biomarkers of islet isolation and transplantation in total pancreatectomy with islet autotransplantation

Abstract: We concluded that miR-375 and miR-200c could potentially serve as novel biomarkers in predicting the islet yield in islet isolation and the metabolic function after transplantation for chronic pancreatitis patients.

Cited by 21 publications

References 42 publications

Islet damage during isolation as assessed by miRNAs and the correlation of miRNA levels with posttransplantation outcome in islet autotransplantation

Islet damage during isolation as assessed by miRNAs and the correlation of miRNA levels with posttransplantation outcome in islet autotransplantation

Assessment of simple indices based on a single fasting blood sample as a tool to estimate beta-cell function after total pancreatectomy with islet autotransplantation - a prospective study

Biomarkers in Islet Cell Transplantation for Type 1 Diabetes

Contact Info

Product

Resources

About