The invention relates to the use of CD34 as a cell surface marker to detect sinoatrial node-like pacemaker cells (SANLPCs) in a population of cells and to generate cell preparations highly enriched for SANLPCs. Also provides herein are methods of using SANLPC-enriched cell preparations for cardiac cell therapy.

The invention relates to the use of CD34 as a cell surface marker to detect sinoatrial node-like pacemaker cells (SANLPCs) in a population of cells and to generate cell preparations highly enriched for SANLPCs. Also provides herein are methods of using SANLPC-enriched cell preparations for cardiac cell therapy.

Compositions of the invention for regenerating defective or absent myocardium comprise an emulsified or injectable extracellular matrix composition. The composition may also include an extracellular matrix scaffold component of any formulation, and further include added cells, proteins, or other components to optimize the regenerative process and restore cardiac function.

Compositions of the invention for regenerating defective or absent myocardium comprise an emulsified or injectable extracellular matrix composition. The composition may also include an extracellular matrix scaffold component of any formulation, and further include added cells, proteins, or other components to optimize the regenerative process and restore cardiac function.

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, is composed at least partly of engineered tissue with genetically engineered cells other than cardiac myocytes. The genetically engineered cells contain a gene encoding a paracrine factor which is under control of an inducible promoter system or a heterologous promoter system. The preparation of the pouch-like structure may be used for therapeutic, disease modelling, and drug development applications.

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, is composed at least partly of engineered tissue with genetically engineered cells other than cardiac myocytes. The genetically engineered cells contain a gene encoding a paracrine factor which is under control of an inducible promoter system or a heterologous promoter system. The preparation of the pouch-like structure may be used for therapeutic, disease modelling, and drug development applications.

Described herein are compositions and techniques related to generation and therapeutic application of stem cell-derived exosomes. The Inventors have discovered cardiosphere-derived cells (CDCs) and their secreted exosomes mediate such inflammatory processes, by, for example, shifting macrophages away from a proinflammatory M1 phenotype toward M2 healing phenotype. This suggests compositions and techniques for use in both long-term reversal of heart and vascular disease pathology, and protection against such disease progression via modulation of inflammation and immune responses.

Described herein are compositions and techniques related to generation and therapeutic application of stem cell-derived exosomes. The Inventors have discovered cardiosphere-derived cells (CDCs) and their secreted exosomes mediate such inflammatory processes, by, for example, shifting macrophages away from a proinflammatory M1 phenotype toward M2 healing phenotype. This suggests compositions and techniques for use in both long-term reversal of heart and vascular disease pathology, and protection against such disease progression via modulation of inflammation and immune responses.

A multi-step stabilization method for connective tissue is described. Stabilized tissues can exhibit increased resistance to degradation due to enzyme activity, fatigue and storage. The multi-step method includes a first step during which the tissue can be incubated with a glycosaminoglycanase inhibitor such as a sulfated oligosaccharide, one example of which being neomycin, a second step during which the tissue can be incubated with a crosslink activator such as a carbodiimide crosslink activator and/or a crosslinking agent such as a heterobifunctional crosslinking agent and/or a phenolic compound such as a tannin, examples of which include tannic acid and pentagalloylglucose, and a third step during which the tissue can be incubated with a second crosslink activator that can be the same or different as the first crosslink activator.

A multi-step stabilization method for connective tissue is described. Stabilized tissues can exhibit increased resistance to degradation due to enzyme activity, fatigue and storage. The multi-step method includes a first step during which the tissue can be incubated with a glycosaminoglycanase inhibitor such as a sulfated oligosaccharide, one example of which being neomycin, a second step during which the tissue can be incubated with a crosslink activator such as a carbodiimide crosslink activator and/or a crosslinking agent such as a heterobifunctional crosslinking agent and/or a phenolic compound such as a tannin, examples of which include tannic acid and pentagalloylglucose, and a third step during which the tissue can be incubated with a second crosslink activator that can be the same or different as the first crosslink activator.