Engineered Tissue Pouch for Heart Distension and Paracrine Support
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Solution Overview
Problem
Current treatments for heart failure, such as drug therapy and device therapy, are inadequate in reversing cardiac dilation and supporting the heart's function, and engineered cardiac structures face challenges in size, immunological tolerance, integration with the host blood supply, and synchronized electrical pulsing.
Innovation Solution
A pouch-like structure composed of engineered tissue with genetically modified cells containing a paracrine factor gene under an inducible promoter system, which can be adapted in size and paracrine activity to support heart function by releasing factors like IGF-1, VEGF, and miR133, enhancing graft survival and myocardial performance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If engineered tissue is used to create pouch-like structures for preventing heart distension, then mechanical support and restraint are provided, but the structure lacks sufficient paracrine support to enhance myocardial performance and graft survival
Solution Approach 1:
The patent combines mechanical support function and paracrine support function into a single integrated pouch-like structure. The engineered tissue is populated with both structural cells (fibroblasts, smooth muscle cells) and genetically modified cells that secrete paracrine factors, allowing the structure to simultaneously provide mechanical restraint and biological support to the heart.
Solution Approach 2:
The pouch-like structure uses composite engineered tissue comprising multiple cell types with different functions. The tissue includes structural cells for mechanical integrity and genetically modified cells for paracrine factor secretion, creating a composite material that delivers both mechanical and biological therapeutic effects.
2Reliability
If genetically modified cells are incorporated into engineered tissue, then paracrine factor secretion is enhanced, but the complexity of preparing the pouch-like structure increases
Solution Approach 1:
The genetically modified cells are prepared in advance before being incorporated into the pouch-like structure. The cells are pre-transduced with viral vectors containing the gene of interest under an inducible promoter, allowing them to be ready for secretion upon implantation without requiring complex in vivo modification procedures.
Solution Approach 2:
Viral vectors serve as intermediaries to deliver genetic material into the cells. The patent uses viral transduction as a mediator to efficiently introduce the gene encoding the paracrine factor into the cells, which then express the factor under control of an inducible promoter system upon implantation.
3Strength
If the pouch-like structure is designed to prevent heart distension, then mechanical restraint is achieved, but integration with host blood supply and electrical synchronization remain challenging
Solution Approach 1:
The pouch-like structure is designed with localized functional zones. Different regions of the engineered tissue contain different cell types and properties tailored to specific requirements: areas in contact with the heart provide mechanical restraint, while other areas are optimized for vascular integration and electrical coupling with host tissue.
Solution Approach 2:
The pouch-like structure is designed to be dynamic rather than static. The genetically modified cells can adjust their paracrine factor secretion in response to local conditions, and the structure can adapt its mechanical properties to accommodate heart movement and growth, enhancing integration with host tissue over time.
Data Source
AI summary
The present invention relates to a pouch-like structure useful for mechanically preventing distension and/or resisting dilation of the heart and for supporting the hearts function by controllable and paracrine support of a failing heart in a mammal. The pouch-like structure is composed at least partly of engineered tissue comprising genetically engineered cells, such as genetically engineered cells other than cardiac myocytes whereby said genetically engineered cells contain a gene encoding a paracrine factor, said gene encoding the paracrine factor being under control of an inducible promoter system or a heterologous promoter system. Further, the present invention relates to a method for the preparation of the pouch-like structure for therapeutic, disease modelling, and drug development applications. In addition, the present invention relates to cells other than cardiac myocytes for use in the preparation of the pouch-like structure as described herein.