scholarly journals TWIST1-reprogrammed endothelial cell transplantation potentiates neovascularization-mediated diabetic wound tissue regeneration

2020 ◽  
Author(s):  
Ada Admin ◽  
Komal Kaushik ◽  
Amitava Das
Keyword(s):  
Cell Transplantation ◽  
Tissue Regeneration ◽  
Meta Analysis ◽  
Diabetic Wound ◽  
Healing Wounds ◽  
Endothelial Genes ◽  
Microarray Datasets ◽  
Endothelial Precursors ◽  
Wound Tissue

Hypo-vascularised diabetic non-healing wounds are due to reduced number and impaired physiology of endogenous endothelial progenitor cell (EPC) population that, limits their recruitment and mobilization at the wound site. To enrich the EPC repertoire from non-endothelial precursors, abundantly available mesenchymal stromal cells (MSCs) were reprogrammed into induced-endothelial cells (iECs). We identified cell signaling molecular targets by meta-analysis of microarray datasets. BMP-2 induction leads to the expression of inhibitory Smad 6/7-dependent negative transcriptional regulation of ID1, rendering the latter's reduced binding to TWIST1 during transdifferentiation of WJ-MSC into iEC. TWIST1, in turn, regulates endothelial genes transcription, positively of pro-angiogenic-<i>KDR</i> and negatively, in part, of anti-angiogenic-<i>SFRP4</i>. Twist1 reprogramming enhanced the endothelial lineage commitment of WJ-MSC, increased the vasculogenic potential of reprogrammed EC (rEC). Transplantation of stable <i>TWIST1</i>-rECs into full-thickness type 1 and 2 diabetic-splinted wound healing murine model enhanced the microcirculatory blood flow and accelerated the wound tissue regeneration. An increased or decreased co-localization of GFP with KDR/SFRP4 and CD31 in the regenerated diabetic wound bed with TWIST1 overexpression or silencing (<i>piLenti-TWIST1-shRNA-GFP</i>), respectively further confirmed improved neovascularization. This study depicted the reprogramming of WJ-MSCs into rECs using unique transcription factors, TWIST1 for an efficacious cell transplantation therapy to induce neovascularization–mediated diabetic wound tissue regeneration.

scholarly journals TWIST1-reprogrammed endothelial cell transplantation potentiates neovascularization-mediated diabetic wound tissue regeneration

2020 ◽  
Author(s):  
Ada Admin ◽  
Komal Kaushik ◽  
Amitava Das
Keyword(s):  
Cell Transplantation ◽  
Tissue Regeneration ◽  
Meta Analysis ◽  
Diabetic Wound ◽  
Healing Wounds ◽  
Endothelial Genes ◽  
Microarray Datasets ◽  
Endothelial Precursors ◽  
Wound Tissue

Hypo-vascularised diabetic non-healing wounds are due to reduced number and impaired physiology of endogenous endothelial progenitor cell (EPC) population that, limits their recruitment and mobilization at the wound site. To enrich the EPC repertoire from non-endothelial precursors, abundantly available mesenchymal stromal cells (MSCs) were reprogrammed into induced-endothelial cells (iECs). We identified cell signaling molecular targets by meta-analysis of microarray datasets. BMP-2 induction leads to the expression of inhibitory Smad 6/7-dependent negative transcriptional regulation of ID1, rendering the latter's reduced binding to TWIST1 during transdifferentiation of WJ-MSC into iEC. TWIST1, in turn, regulates endothelial genes transcription, positively of pro-angiogenic-<i>KDR</i> and negatively, in part, of anti-angiogenic-<i>SFRP4</i>. Twist1 reprogramming enhanced the endothelial lineage commitment of WJ-MSC, increased the vasculogenic potential of reprogrammed EC (rEC). Transplantation of stable <i>TWIST1</i>-rECs into full-thickness type 1 and 2 diabetic-splinted wound healing murine model enhanced the microcirculatory blood flow and accelerated the wound tissue regeneration. An increased or decreased co-localization of GFP with KDR/SFRP4 and CD31 in the regenerated diabetic wound bed with TWIST1 overexpression or silencing (<i>piLenti-TWIST1-shRNA-GFP</i>), respectively further confirmed improved neovascularization. This study depicted the reprogramming of WJ-MSCs into rECs using unique transcription factors, TWIST1 for an efficacious cell transplantation therapy to induce neovascularization–mediated diabetic wound tissue regeneration.

Time in range for multiple technologies in type 1 diabetes: a systematic review and network meta-analysis

2020 ◽  
Author(s):  
Anthony Pease ◽  
Clement Lo ◽  
Arul Earnest ◽  
Velislava Kiriakova ◽  
Danny Liew ◽  
...  
Keyword(s):  
Systematic Review ◽  
Type 1 Diabetes ◽  
Closed Loop ◽  
Meta Analysis ◽  
Management Strategies ◽  
Glucose Testing ◽  
Closed Loop Systems ◽  
Percent Time ◽  
Time In Range

<b>Background: </b>Time-in-range is a key glycaemic metric, and comparisons of management technologies for this outcome are critical to guide device selection. <p><b> </b></p> <p><b>Purpose: </b>We conducted a systematic review and network meta-analysis to compare and rank technologies for time in glycaemic ranges.</p> <p> </p> <p><b>Data sources: </b>We searched All Evidenced Based Medicine Reviews, CINAHL, EMBASE, MEDLINE, MEDLINE In-Process and other non-indexed citations, PROSPERO, PsycINFO, PubMed, and Web of Science until 24 April, 2019.</p> <p> </p> <p><b>Study selection: </b>We included randomised controlled trials <u>></u>2 weeks duration comparing technologies for management of type 1 diabetes in adults (<u>></u>18 years of age), excluding pregnant women. </p> <p> </p> <p><b>Data extraction: </b>Data were extracted using a predefined template. Outcomes were percent time with sensor glucose levels 3.9–10.0mmol/l (70–180mg/dL), >10.0mmol/L (180mg/dL), and <3.9mmol/L (70mg/dL). </p> <p><b> </b></p> <p><b>Data synthesis: </b>We identified 16,772 publications, of which 14 eligible studies compared eight technologies comprising 1,043 participants. Closed loop systems lead to greater percent time-in-range than any other management strategy and was 17.85 (95% predictive interval [PrI] 7.56–28.14) higher than usual care of multiple daily injections with capillary glucose testing. Closed loop systems ranked best for percent time-in-range or above range utilising surface under the cumulative ranking curve (SUCRA–98.5 and 93.5 respectively). Closed loop systems also ranked highly for time below range (SUCRA–62.2). </p> <p><b> </b></p> <p><b>Limitations: </b>Overall risk of bias ratings were moderate for all outcomes. Certainty of evidence was very low.</p> <p><b> </b></p> <p><b>Conclusions: </b>In the first integrated comparison of multiple management strategies considering time-in-range, we found that the efficacy of closed loop systems appeared better than all other approaches. </p>

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