Woldendorp K, Selvaraj CN, Bannon PG, Dubenec S
J. Thorac. Cardiovasc. Surg. 2019 05;157(5):e223-e225
PMID: 30527780
Woldendorp K, Selvaraj CN, Bannon PG, Dubenec S
J. Thorac. Cardiovasc. Surg. 2019 05;157(5):e223-e225
PMID: 30527780
Tan RP, Chan AHP, Lennartsson K, Miravet MM, Lee BSL, Rnjak-Kovacina J, Clayton ZE, Cooke JP, Ng MKC, Patel S, Wise SG
Stem Cell Res Ther 2018 03;9(1):70
PMID: 29562916
BACKGROUND: Induced pluripotent stem-cell derived endothelial cells (iPSC-ECs) can be generated from any somatic cell and their iPSC sources possess unlimited self-renewal. Previous demonstration of their proangiogenic activity makes them a promising cell type for treatment of ischemic injury. As with many other stem cell approaches, the low rate of in-vivo survival has been a major limitation to the efficacy of iPSC-ECs to date. In this study, we aimed to increase the in-vivo lifetime of iPSC-ECs by culturing them on electrospun polycaprolactone (PCL)/gelatin scaffolds, before quantifying the subsequent impact on their proangiogenic function.
METHODS: iPSC-ECs were isolated and stably transfected with a luciferase reporter to facilitate quantification of cell numbers and non-invasive imaging in-vivo PCL/gelatin scaffolds were engineered using electrospinning to obtain woven meshes of nanofibers. iPSC-ECs were cultured on scaffolds for 7 days. Subsequently, cell growth and function were assessed in vitro followed by implantation in a mouseback subcutaneous model for 7 days.
RESULTS: Using a matrix of conditions, we found that scaffold blends with ratios of PCL:gelatin of 70:30 (PG73) spun at high flow rates supported the greatest levels of iPSC-EC growth, retention of phenotype, and function in vitro. Implanting iPSC-ECs seeded on PG73 scaffolds in vivo improved their survival up to 3 days, compared to cells directly injected into control wounds, which were no longer observable within 1 h. Enhanced engraftment improved blood perfusion, observed through non-invasive laser Doppler imaging. Immunohistochemistry revealed a corresponding increase in host angiogenic mechanisms characterized by the enhanced recruitment of macrophages and the elevated expression of proangiogenic cytokines vascular endothelial growth factor and placental growth factor.
CONCLUSIONS: Knowledge of these mechanisms combined with a deeper understanding of the scaffold parameters influencing this function provides the groundwork for optimizing future iPSC-EC therapies utilizing engraftment platforms. The development of combined scaffold and iPSC-EC therapies could ultimately improve therapeutic angiogenesis and the treatment of ischemic injury.
Zhao DF, Edelman JJ, Seco M, Bannon PG, Vallely MP
J. Am. Coll. Cardiol. 2018 Nov;72(21):2679-2680
PMID: 30466529
Edelman JJ, Thourani VH
J. Thorac. Cardiovasc. Surg. 2018 Dec;156(6):2135-2137
PMID: 30449571
Austin DE, Burns B, Lowe D, Cartwright B, Clarke A, Dennis M, D’Souza M, Nathan R, Bannon PG, Gattas D, Connellan M, Forrest P
Anaesth Intensive Care 2018 Nov;46(6):579-588
PMID: 30447667
In New South Wales, a coordinated extracorporeal membrane oxygenation (ECMO) retrieval program has been in operation since 2007. This study describes the characteristics and outcomes of patients transported by this service. We performed a retrospective observational study and included patients who were transported on ECMO to either of two adult tertiary referral hospitals in Sydney, New South Wales, between February 28, 2007 and February 29, 2016. One hundred and sixty-four ECMO-facilitated transports occurred, involving 160 patients. Of these, 118 patients (74%) were treated with veno-venous (VV) ECMO and 42 patients (26%) were treated with veno-arterial ECMO. The mean (standard deviation, SD) age was 40.4 (15.0) years. Seventy-seven transports (47%) occurred within metropolitan Sydney, 52 (32%) were from rural or regional areas within NSW, 17 (10%) were interstate transfers and 18 (11%) were international transfers. Transfers were by road (58%), fixed wing aircraft (27%) or helicopter (15%). No deaths occurred during transport. The median (interquartile range) duration of ECMO treatment was 8.9 (5.2-15.3) days. One hundred and nineteen patients (74%) were successfully weaned from ECMO and 109 (68%) survived to hospital discharge or transfer. In patients treated with VV ECMO, age, sequential organ failure assessment score, pre-existing immunosuppressive disease, pre-existing diabetes, renal failure requiring dialysis and failed prone positioning prior to ECMO were independently associated with increased mortality. ECMO-facilitated patient transport is feasible, safe, and results in acceptable short-term outcomes. The NSW ECMO Retrieval Service provides specialised support to patients with severe respiratory and cardiovascular illness, who may otherwise be too unstable to undergo inter-hospital transfer to access advanced cardiovascular and critical care services.
Clayton ZE, Tan RP, Miravet MM, Lennartsson K, Cooke JP, Bursill CA, Wise SG, Patel S
Biosci. Rep. 2018 08;38(4)
PMID: 29976773
Chronic wounds are a major complication in patients with cardiovascular diseases. Cell therapies have shown potential to stimulate wound healing, but clinical trials using adult stem cells have been tempered by limited numbers of cells and invasive procurement procedures. Induced pluripotent stem cells (iPSCs) have several advantages of other cell types, for example they can be generated in abundance from patients’ somatic cells (autologous) or those from a matched donor. iPSCs can be efficiently differentiated to functional endothelial cells (iPSC-ECs). Here, we used a murine excisional wound model to test the pro-angiogenic properties of iPSC-ECs in wound healing. Two full-thickness wounds were made on the dorsum of NOD-SCID mice and splinted. iPSC-ECs (5 × 10) were topically applied to one wound, with the other serving as a control. Treatment with iPSC-ECs significantly increased wound perfusion and accelerated wound closure. Expression of endothelial cell (EC) surface marker, platelet endothelial cell adhesion molecule (PECAM-1) (CD31), and pro-angiogenic EC receptor, Tie1, mRNA was up-regulated in iPSC-EC treated wounds at 7 days post-wounding. Histological analysis of wound sections showed increased capillary density in iPSC-EC wounds at days 7 and 14 post-wounding, and increased collagen content at day 14. Anti-GFP fluorescence confirmed presence of iPSC-ECs in the wounds. Bioluminescent imaging (BLI) showed progressive decline of iPSC-ECs over time, suggesting that iPSC-ECs are acting primarily through short-term paracrine effects. These results highlight the pro-regenerative effects of iPSC-ECs and demonstrate that they are a promising potential therapy for intractable wounds.
Joshi P, Thakur S, Finn C, Sadlier P
J. Heart Valve Dis. 2017 11;26(6):744-746
PMID: 30207130
The case described here is the first reported case of successful isolated aortic valve replacement (AVR) via a right anterior thoracotomy (RAT) in a patient with osteogenesis imperfecta (OI). The most common reported complication in patients with OI undergoing AVR or other cardiac surgery is bleeding and sternal complications. By using a RAT approach, it was possible to replace the aortic valve without major bleeding, transfusion, or sternal complications.