Intracoronary device and method of use thereof

Abstract

Engraftment of therapeutic cells and agents to a target site in an organism is enhanced by mechanical, chemical and biological methods and systems.

Description

TECHNICAL FIELD [0001] This document relates generally to delivery of therapeutic cells to a target site of a mammal and in particular, to a method and apparatus for enhancing engraftment at the target site. BACKGROUND OF THE INVENTION [0002] Damaged tissue, such as a lesion in a vessel, can be treated with therapeutic cells. For example, therapeutic cells can be injected into the vasculature to treat a lesion in the vessel. Some therapeutic cells will attach to the target site and provide treatment to the damaged tissue. However, depending on factors such as the dimensions of the target site, some of the therapeutic cells will flow past the lesion site without attaching to the site. Those therapeutic cells that fail to attach provide no benefit. Moreover, it has been reported that autologous bone marrow cells isolated from patients with chronic heart failure have “significantly reduced migratory and colony forming activity in vitro and a reduced neovascularization capacity in vivo”...

AI Technical Summary

Benefits of technology

[0004] Various embodiments of the present subject matter provide enhanced migratory function, enhanced adhesion probability, increased residence time (for example longer residence time of the therapeutic cell in the coronary arteries), increased engraftment and increased likelihood of therapeutic potential. The methods and system disclosed herein include adding agents or secondary processing aimed at improving delivery and engraftment of delivered cells.

[0010] The methods of the present invention further comprise conditioning cells associated with the target site to provide target cells having an altered number of adhesion molecules as compared to corresponding target cells not subjected to the conditioning, wherein the conditioning increases the probability of engraftment of the therapeutic cells at the target site.

[0014] The present invention also provides a method of enhancing engraftment of a therapeutic cell at a target site in a mammal comprising subjecting the therapeutic cell to in vitro conditioning, wherein the conditioning increases the probability of engraftment of the therapeutic cell at the target site; and delivering a composition comprising the conditioned therapeutic cell, wherein the composition is delivered to the target site using an implantable delivery device.

[0016] The present invention also provides a method comprising inducing ischemia at a target site for a transitory period of time, delivering a therapeutic cell and a viscous agent to the target site, the viscous agent selected to increase a viscosity of the therapeutic cell, and restoring normal blood flow to the target site.

[0018] Also provided by the present invention is a method comprising modifying a target cell to upregulate an adhesion molecule counter-receptor, subjecting a therapeutic cell to mechanical conditioning so as to provide an increased number of adhesion molecules on the cell surface as compared to a non-conditioned cell, and delivering the therapeutic cell to the site of the target cell.

Problems solved by technology

Those therapeutic cells that fail to attach provide no benefit.

The inability of such cells to migrate may lead to limited engraftment and colony forming activity may contribute to “limited therapeutic potential.”

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