Abstract
Summary
Previous attempts in cardiac bioengineering have failed to provide tissues for cardiac regeneration. Recent advances in 3-dimensional bioprinting technology using prevascularized ...myocardial microtissues as ‘bioink’ have provided a promising way forward. This review guides the reader to understand why myocardial tissue engineering is difficult to achieve and how revascularization and contractile function could be restored in 3-dimensional bioprinted heart tissue using patient-derived stem cells.
Ischaemic heart disease remains the leading global cause of mortality and is rising in prevalence with population growth, ageing effects and shifting epidemiological trends 1, 2.
Abstract
OBJECTIVES
...Preclinical in vivo studies using omental tissue as a biomaterial for myocardial regeneration are promising and have not previously been collated. We aimed to evaluate the effects of the omentum as a support for bioengineered tissue therapy for cardiac regeneration in vivo.
METHODS
A systematic scoping review was performed. Only English-language studies that used bioengineered cardio-regenerative tissue, omentum and ischaemic cardiomyopathy in vivo models were included.
RESULTS
We initially screened 1926 studies of which 17 were included in the final qualitative analysis. Among these, 11 were methodologically comparable and 6 were non-comparable. The use of the omentum improved the engraftment of bioengineered tissue by improving cell retention and reducing infarct size. Vascularization was also improved by the induction of angiogenesis in the transplanted tissue. Omentum-supported bioengineered grafts were associated with enhanced host reverse remodelling and improved haemodynamic measurements.
CONCLUSIONS
The omentum is a promising support for myocardial regenerative bioengineering in vivo. Future studies would benefit from more homogenous methodologies and reporting of outcomes to allow for direct comparison.
Reply to Yurekli et al Wang, Hogan; Roche, Christopher D; Gentile, Carmine
European journal of cardio-thoracic surgery,
10/2021, Letnik:
60, Številka:
4
Journal Article
Current inflammatory bowel disease (IBD) therapies are ineffective in a high proportion of patients. Combining bulk and single-cell transcriptomics, quantitative histopathology and in situ ...localization across three cohorts of patients with IBD (total n = 376), we identify coexpressed gene modules within the heterogeneous tissular inflammatory response in IBD that map to distinct histopathological and cellular features (pathotypes). One of these pathotypes is defined by high neutrophil infiltration, activation of fibroblasts and vascular remodeling at sites of deep ulceration. Activated fibroblasts in the ulcer bed display neutrophil-chemoattractant properties that are IL-1R, but not TNF, dependent. Pathotype-associated neutrophil and fibroblast signatures are increased in nonresponders to several therapies across four independent cohorts (total n = 343). The identification of distinct, localized, tissular pathotypes will aid precision targeting of current therapeutics and provides a biological rationale for IL-1 signaling blockade in ulcerating disease.
With the increasing prevalence of type 2 diabetes and fatty liver disease, there is still an unmet need to better treat hyperglycemia and hyperlipidemia. Here, we identify isthmin-1 (Ism1) as an ...adipokine and one that has a dual role in increasing adipose glucose uptake while suppressing hepatic lipid synthesis. Ism1 ablation results in impaired glucose tolerance, reduced adipose glucose uptake, and reduced insulin sensitivity, demonstrating an endogenous function for Ism1 in glucose regulation. Mechanistically, Ism1 activates a PI3K-AKT signaling pathway independently of the insulin and insulin-like growth factor receptors. Notably, while the glucoregulatory function is shared with insulin, Ism1 counteracts lipid accumulation in the liver by switching hepatocytes from a lipogenic to a protein synthesis state. Furthermore, therapeutic dosing of recombinant Ism1 improves diabetes in diet-induced obese mice and ameliorates hepatic steatosis in a diet-induced fatty liver mouse model. These findings uncover an unexpected, bioactive protein hormone that might have simultaneous therapeutic potential for diabetes and fatty liver disease.
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•The secreted protein ISM1 increases adipocyte glucose uptake•ISM1 ablation impairs basal and insulin-induced glucose uptake by adipocytes•ISM1 suppresses hepatocyte lipid synthesis while increasing protein synthesis•Therapeutic administration of recombinant ISM1 improves diabetes and hepatic steatosis
Here, Jiang et al. describe the discovery of isthmin-1 (ISM1) as an adipose-secreted polypeptide hormone. ISM1 has dual roles in increasing adipocyte glucose uptake while suppressing hepatic lipid synthesis, thus improving hyperglycemia and reducing lipid accumulation in mouse models. ISM1, therefore, may offer a new therapeutic opportunity to simultaneously treat diabetes and fatty liver disease.
Testing regenerative properties of 3D bioprinted cardiac patches in vivo using murine models of heart failure via permanent left anterior descending (LAD) ligation is a challenging procedure and has ...a high mortality rate due to its nature. We developed a method to consistently transplant bioprinted patches of cells and hydrogels onto the epicardium of an infarcted mouse heart to test their regenerative properties in a robust and feasible way. First, a deeply anesthetized mouse is carefully intubated and ventilated. Following left lateral thoracotomy (surgical opening of the chest), the exposed LAD is permanently ligated and the bioprinted patch transplanted onto the epicardium. The mouse quickly recovers from the procedure after chest closure. The advantages of this robust and quick approach include a predicted 28-day mortality rate of up to 30% (lower than the 44% reported by other studies using a similar model of permanent LAD ligation in mice). Moreover, the approach described in this protocol is versatile and could be adapted to test bioprinted patches using different cell types or hydrogels where high numbers of animals are needed to optimally power studies. Overall, we present this as an advantageous approach which may change preclinical testing in future studies for the field of cardiac regeneration and tissue engineering.
Damaged cardiac tissues could potentially be regenerated by transplanting bioengineered cardiac patches to the heart surface. To be fully paradigm-shifting, such patches may need to be transplanted ...using minimally invasive robotic cardiac surgery (not only traditional open surgery). Here, we present novel robotic designs, initial prototyping and a new surgical operation for instruments to transplant patches
robotic minimally invasive heart surgery.
Robotic surgical instruments and automated control systems were designed, tested with simulation software and prototyped. Surgical proof-of-concept testing was performed on a pig cadaver.
Three robotic instrument designs were developed. The first (called "Claw" for the claw-like patch holder at the tip) operates on a rack and pinion mechanism. The second design ("Shell-Beak") uses adjustable folding plates and rods with a bevel gear mechanism. The third ("HeartStamp") utilizes a stamp platform protruding through an adjustable ring. For the HeartStamp, rods run through a cylindrical structure designed to fit a uniportal Video-Assisted Thorascopic Surgery (VATS) surgical port. Designed to work with or without a sterile sheath, the patch is pushed out by the stamp platform as it protrudes. Two instrument robotic control systems were designed, simulated
and one of these underwent early 'sizing and learning' prototyping as a proof-of-concept. To reflect real surgical conditions, surgery was run "live" and reported exactly (as-it-happened). We successfully picked up, transferred and released a patch onto the heart using the HeartStamp in a pig cadaver model.
These world-first designs, early prototypes and a novel surgical operation pave the way for robotic instruments for automated keyhole patch transplantation to the heart. Our novel approach is presented for others to build upon free from restrictions or cost-potentially a significant moment in myocardial regeneration surgery which may open a therapeutic avenue for patients unfit for traditional open surgery.
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