External magnetic force for targeted cell delivery with enhanced cell retention

A cell and magnetic technology, applied in the fields of magnetic fields generated by permanent magnets, magnetic therapy, and drugs, etc., can solve the problem of low cell retention rate

Inactive Publication Date: 2012-09-19
CEDARS SINAI MEDICAL CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, major challenges remain in the delivery and localization of cells to target tissues or organs such as the heart
Additionally, post-delivery cell retention was low regardless of the delivery method

Method used

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  • External magnetic force for targeted cell delivery with enhanced cell retention
  • External magnetic force for targeted cell delivery with enhanced cell retention
  • External magnetic force for targeted cell delivery with enhanced cell retention

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0239] Example 1: Isolation of Cardiac-Derived Stem Cells from Cardiac Biopsy Samples

[0240] Isolation of pluripotent stem cells from a cardiac biopsy or other cardiac tissue can be accomplished by any known method, such as the multi-step method described in US Publication No. 2008 / 026792, which is incorporated herein by reference.

[0241] Using this method, cardiac tissue is first obtained by percutaneous intramyocardial biopsy or by sterile dissection of the heart. However, it should be understood that in other embodiments, the initial tissue may be obtained by other methods (eg, surgical samples, fresh cadaver tissue, etc.). In some embodiments, harvesting of fresh tissue is not necessary since stem cells that have been previously isolated and stored (eg, cryopreserved) are used. Once obtained, tissue samples were kept on ice in high potassium cardioplegia (containing 5% glucose, 68.6 mmol / L mannose, 12.5 meq potassium chloride, and 12.5 meq sodium bicarbonate with 10...

Embodiment 2

[0245] Example 2: Isolation of porcine heart-derived cells

[0246] Porcine CDCs were isolated and cultured according to Davis et al., (2009) P10S One 4(9):e7195. Briefly, porcine myocardium samples were collected from the right ventricular septum using a biopsy knife. Biopsy samples were kept on ice in high potassium cardioplegia (5% glucose, 68.6 mM mannose, 12.5 meq potassium chloride, and 12.5 meq sodium bicarbonate and 10 units / mL heparin) to preserve tissue viability during transport . Tissues are processed within 2 hours. Myocardium samples were then sliced ​​to less than 1mm 3 Fragments were washed and partially digested with collagenase. These tissue fragments were used as cardiac grafts in fibronectin (20 μg / mL; Sigma) coated dishes in cardiac transplantation medium (CEM; Iscove's Modified Dulbecco's Medium (GIBCO), fetal bovine serum (10% ( Piglets only); HyC10ne, 10gan, UT), 100 units / mL penicillin G (GIBCO), 100 μg / mL streptomycin (GIBCO), 2 mmol / L L-glutam...

Embodiment 3

[0247] Example 3: Tagging CDC with SPIO

[0248] SPIO microsphere particles (0.9-pm diameter, Bangs Laboratories, IN) and CDCs (1x10 in 15ml medium 6 Cells) were cultured in T75 flasks at a ratio of microspheres to cells of 500:1. As discussed herein, other ratios of microspheres (or other labeled particles) to cells (e.g., 100:1; 250:1; 1000:1; 2000:1, 4000:1, etc.) may be used in some embodiments ). Cells were incubated at 37°C and 95% air / 5% CO 2 conditions to introduce SPIO into the cells.

[0249] Labeling efficiency was evaluated by microscopy and flow cytometry. SPIO (with a dark green fluorescent label) overnight labeled CDC was examined with a fluorescence microscope (excitation 488 nm; emission 520 nm). A green color is observed, which indicates that the cells were successfully labeled by SPIO (see figure 1 ). Labeling efficiency was also analyzed by flow cytometry. As shown in Figure 2, when SPIO-labeled cells exhibited green fluorescence, the histograms w...

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Abstract

Disclosed herein are compositions and methods for the improved delivery of cells to a target tissue. In some embodiments, the compositions comprise stem cells, in particular cardiac stem cells, and the target tissue is damaged or diseased cardiac tissue. In several embodiments, the methods, in combination with the compositions, yield enhanced delivery, retention, and / or engraftment of the cells into the target tissue, thereby inducing improved functional recovery.

Description

[0001] Cross reference to related applications [0002] This application claims priority to US Provisional Application No. 61 / 255,438, filed October 27, 2009, the disclosure of which is expressly incorporated herein by reference. [0003] Statement Regarding Federally Funded Research and Development (R&D) [0004] This invention was made with government support under a RO1 grant, NIH contract HL083109, awarded by the National Heart, Lung, and Blood Institute. The government has certain rights in this invention. technical field [0005] Embodiments of the present application generally relate to compositions and methods for enhanced delivery, retention and / or transplantation of cells into target tissues or organs using cell magnetization, optionally in combination with one or more vascular permeability agents. In particular, cardiac cells can be delivered to damaged cardiac tissue, the enhanced delivery, retention and / or engraftment of said cells assisting in the repair and / or...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61M37/00A61N2/00
CPCA61M25/04A61M25/0068A61N2/002A61M25/0133A61N2/06A61M25/10A61M25/0082
Inventor E·马尔万程柯
Owner CEDARS SINAI MEDICAL CENT
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