Surgery – Magnetic field applied to body for therapy – Magnetic element placed within body
Reexamination Certificate
1998-12-31
2001-03-20
Gilbert, Samuel G. (Department: 3736)
Surgery
Magnetic field applied to body for therapy
Magnetic element placed within body
Reexamination Certificate
active
06203487
ABSTRACT:
BACKGROUND OF THE INVENTION
Local delivery of therapeutics to the site of action in the body is often desired. For example, bronchodilator drugs are most effective when inhaled directly into the lungs, avoiding systemic circulation which can lead to rapid metabolism of compounds as well as effects at tissues other than the target sites. In the same way, targeted or focal delivery of cells, as part of a therapeutic regimen, would be useful to avoid potential side effects of cell treatment as well as metabolism by the body.
Accordingly, focal delivery of cells in the human body has been an active area of research. Cells have been explored as means of gene transfer to the brain, instead of viral vectors (Taylor, R., 1997
Neuromuscul. Disord.,
7:343-351); neural precursor cells containing genes encoding deficient enzymes were transplanted into mouse models of neurodegenerative disease. Engineered urothelial cells have also been locally implanted to produce a functional neo-organ (Yoo, J. J. and A. Atala, 1997
J. Urol.,
158:1066-1070). Encapsulated genetically engineered cells that continuously released ciliary neurotrophic factor have also been tested in humans and animals (Tan, S. A. et al., 1996
Cell Transplant.,
5:577-587).
Paramagnetic particles and paramagnetic techniques are used in medicine in a variety of ways. For example, paramagnetic contrast media have been described by Catalano, C. et al., 1995
Radiol. Med.,
89:825-830; Jackler, R. K. et al., 1990
Otolaryngol. Head Neck Surg.,
102:70-77; and Bonnet, P. A. et al., 1990
Magn. Reson. Imaging,
8:71-77. A hepatocyte-specific contrast media that allows for specific imaging of hepatitis has also been described by Tanimoto, A. et al., 1993
J. Magn. Reson. Imaging,
3:786-793. Paramagnetic substances are also used in analytical chemical assays.
Internalized magnetic particles have also been used to study inflammation. For example, Yeh et al., 1993
MRM,
30:617-625 and 1995
MRM,
33:200-208, demonstrated that rat T-cells that have internalized dextran-coated iron oxide particles can be used to identify areas of inflammation by magnetic resonance imaging. Similarly, Krieg et al., 1995
Magn. Reson. Imagine,
13:393-400, demonstrated that neutrophils that had previously phagocytosed polystyrene-embedded magnetite micro crystals could be used to identify sites of inflammation on T2-weighted magnetic resonance images.
It has now been found that magnetic particles can be used in the focal delivery of cells. In the present invention, a new method for targeted delivery of cells is provided using magnetic particle-containing cells and a magnetic field which ensures adequate attachment of cells to the target tissue. Once attached, cells and their products are available for local activity.
SUMMARY OF THE INVENTION
An object of the present invention is to provide a method of delivering selected cells to a target tissue in an animal which comprises culturing selected cells so that the selected cells internalize magnetic particles; administering the selected cells containing the internalized magnetic particles to the animal; and placing a magnetic field around the target tissue in the animal so that the selected cells move to the target tissue of the animal and facilitate focal delivery of the cells to the target tissue.
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Yeh et al., “Intracellular Labeling of T-Cells with Superparamagnetic Contrast Agents”Magnetic Resonance in Medicine30(5):617-625 (1993).
Yeh et al., “In Vivo Dynamic MRI Tracking of Rat T-Cells Labeled with Superparamagnetic Iron-Oxide Particles”Magnetic Resonance in Medicine33(2):200-208 (1995).
Krieg et al., “Superparamagnetically labeled neutrophils as potential abscess-specific contrast agent for MRI”,Magnetic Resonance Imaging13(3):393-400 (1995) (PubMed abstract only).
Cadugan Joseph A.
Gilbert Samuel G.
Smith Janet B.
Thomas Jefferson University
Weber, Esq. Clifford K.
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