IP Library Granted Patent US 12,280,112
Granted Patent B2
US 12,280,112 · App. 17/286,210 · Granted Apr 22, 2025

Magnetic delivery system and hydrogel fixative for therapeutic cells

Inventors: David A. Vorp (Pittsburgh, PA); Aneesh Krishna Ramaswamy (Pittsburgh, PA); Justin Sol Weinbaum (Allison Park, PA); Kory James Blose (Pittsburgh, PA); Timothy Kwang-Joon Chung (Pittsburgh, PA); Trevor Kickliter (Allentown, PA); Yogev Baruch (Pittsburgh, PA); John A. Curci (Nashville, TN)
Assignees: University of Pittsburgh—Of the Commonwealth System of Higher Education; Vanderbilt University
A61K41/00A61K35/28A61M5/1407A61M25/0127A61M25/09041C12N5/0667A61M2202/09A61M2205/0288
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,280,112
App. No.
17/286,210
Granted
Apr 22, 2025
Kind
B2
Abstract

A method of delivering cells to a target tissue is provided comprising depositing a hydrogel pre-gel comprising magnetic particle-loaded cells to the target tissue and, prior to or during gelation of the hydrogel, drawing the magnetic particle-loaded cells to the tissue with a magnetic field, followed by gelation of the hydrogel to lock the cells in place on the tissue. The cells may be mesenchymal stem cells, such as adipose-derived mesenchymal stem cells, and the target tissue may be adventitial tissue of an aneurysm in a blood vessel. Also provided are devices useful in the method.

Claims (18)

1. A method of delivering a cell to an aortic aneurysm, comprising:

mixing cells comprising internalized magnetic particles with a hydrogel pre-gel composition;

depositing the pre-gel composition comprising the cells at a site on or adjacent to a tissue, under conditions suitable for gelation of the pre-gel composition such that the pre-gel composition forms a hydrogel at the site; and

prior or during gelation of the hydrogel, applying a magnetic field to the cells in the deposited pre-gel to draw the cells to the aneurysm.

2. The method of claim 1 , wherein the cells are targeted to adventitia in the aneurysm.

3. The method of claim 1 , wherein the pre-gel composition comprises a thermoresponsive polymer composition and forms a hydrogel at 37° C.

4. The method of claim 1 , wherein one or more compounds or compositions in the pre-gel composition undergoes a chemical reaction to produce the hydrogel.

5. The method of claim 4 , wherein the pre-gel composition comprises thrombin and fibrinogen.

6. The method of claim 5 , wherein the pre-gel composition comprises from 0.1 mg/mL to 15 mg/mL fibrinogen.

7. The method of claim 1 , wherein the cell is a pluripotent cell, a stem cell, a multipotent cell, or a progenitor cell.

8. The method of claim 1 , wherein the cell is a mesenchymal stem cell.

9. The method of claim 1 , wherein the magnetic particles are ferromagnetic nanoparticles having a diameter ranging from 1 nm to 500 nm.

10. The method of claim 1 , further comprising adding the magnetic particles to cell culture media comprising cells and culturing the cells with the magnetic particles to produce the cells comprising internalized magnetic particles.

11. A method of treating an abdominal aortic aneurysm, in a patient, comprising delivering mesenchymal stem cells (MSCs) to adventitia on or about the aneurysm by depositing a pre-gel composition comprising MSCs comprising internalized magnetic particles at a site on or adjacent to a tissue, under conditions suitable for gelation of the pre-gel composition such that the pre-gel composition forms a hydrogel at the site; and prior to or during gelation of the hydrogel, applying a magnetic field to the cells in the deposited pre-gel to draw the cells to the tissue.

12. The method of claim 11 , wherein the MSCs are adipose-derived mesenchymal stem cells.

13. The method of claim 11 , wherein the patient is human.

14. The method of claim 11 , further comprising, prior to depositing the pre-gel composition comprising MSCs comprising internalized magnetic particles at a site on or adjacent to the tissue, mixing MSCs comprising internalized magnetic particles with a hydrogel pre-gel composition to produce the pre-gel composition comprising MSCs comprising internalized magnetic particles.

15. The method of claim 11 , wherein the pre-gel comprises fibrinogen and thrombin.

Assignments (4)
CONFIRMATORY LICENSE Recorded Dec 4, 2023
From: UNIVERSITY OF PITTSBURGH
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 065771/0579 →
CORRECTIVE ASSIGNMENT TO CORRECT THE SECOND INVENTOR'S NAME PREVIOUSLY RECORDED AT REEL: 055944 FRAME: 0590. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded May 18, 2021
From: VORP, DAVID A.; RAMASWAMY, ANEESH KRISHNA; WEINBAUM, JUSTIN SOL; BLOSE, KORY JAMES; CHUNG, TIMOTHY KWANG-JOON; KICKLITER, TREVOR; BARUCH, YOGEV
To: UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION
Reel/Frame 056358/0060 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 16, 2021
From: VORP, DAVID A.; KRISHNA, ANEESH KRISHNA; WEINBAUM, JUSTIN SOL; BLOSE, KORY JAMES; CHUNG, TIMOTHY KWANG-JOON; KICKLITER, TREVOR; BARUCH, YOGEV
To: UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION
Reel/Frame 055944/0590 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 16, 2021
From: CURCI, JOHN A.
To: VANDERBILT UNIVERSITY
Reel/Frame 055944/0625 →
Continuity (2)
Provisional Application 62747767 · Oct 19, 2018
Related Publication 20210338816A1 · Nov 4, 2021
References Cited (32)
US 8673323B2 · Thomopoulos et al. · 2014 [cited by applicant]
US 20060041182A1 · Forbes et al. · 2006 [cited by applicant]
US 20080160085A1 · Boland et al. · 2008 [cited by applicant]
US 20100028311A1 · Motlagh et al. · 2010 [cited by applicant]
US 20100209398A1 · Tankovich · 2010 [cited by examiner]
US 20120214217A1 · Grogan · 2012 [cited by examiner]
US 20120253102A1 · Marban et al. · 2012 [cited by applicant]
US 20130261373A1 · Pison et al. · 2013 [cited by applicant]
US 20150112299A1 · Forbes et al. · 2015 [cited by applicant]
US 20150313995A1 · Hung · 2015 [cited by applicant]
US 20180133401A1 · Schwab et al. · 2018 [cited by applicant]
US 20190175495A1 · Taylor · 2019 [cited by examiner]
WO 2014093581A1 · 2014 [cited by applicant]
Bensaïd et al., “A biodegradable fibrin scaffold for mesenchymal stem cell transplantation”, Biomaterials, 2003, pp. 2497-2502, vol. 24. [cited by applicant]
Blose et al., “Periadventitial adipose-derived stem cell treatment halts elastase-induced abdominal aortic aneurysm progression”, Regen Med., Nov. 2014, pp. 733-741, vol. 9:6. [cited by applicant]
Chung et al., “Magnetic field assisted localization of ADMSCs with iron nanoparticles”, McGowan Retreat, 2018, 6 pages. [cited by applicant]
Consigny et al., “Use of Endothelial Cells Containing Superparamagnetic Microspheres to Improve Endothelial Cell Delivery to Arterial Surfaces after Angioplasty”, JVIR, 1999, pp. 155-163, vol. 10. [cited by applicant]
Frese et al., “Adipose Tissue-Derived Stem Cells in Regenerative Medicine”, Transfusion Medicine and Hemotherapy, 2016, pp. 268-274, vol. 43. [cited by applicant]
Hashizume et al., “Mesenchymal stem cells attenuate angiotensin II-induced aortic aneurysm growth in apolipoprotein E-deficient mice”, Journal of Vascular Surgery, Dec. 2011, pp. 1743-1752, vol. 54. [cited by applicant]
Hou et al., “In Vitro Evaluation of a Fibrin Gel Antibiotic Delivery System Containing Mesenchymal Stem Cells and Vancomycin Alginate Beads for Treating Bone Infections and Facilitating Bone Formation”, Tissue Engineeri… [cited by applicant]
Kickliter et al., “Adventitial Delivery of Adipose-Derived Mesenchymal Stem Cells to Large Animal Aortas”, University of Pittsburgh Presentation, 2018, 1 page. [cited by applicant]
Kontopodis et al., “The-Not So-Solid 5.5 cm Threshold for Abdominal Aortic Aneurysm Repair: Facts, Misinterpretations, and Future Directions”, Frontiers in Surgery, Jan. 2016, 6 pages, vol. 3. [cited by applicant]
Kurosawa et al., “Current Status of Medical Treatment for Abdominal Aortic Aneurysm”, Circulation Journal, Dec. 2013, pp. 2860-2866, vol. 77. [cited by applicant]
Ludwig et al., “Structural properties of magnetic nanoparticles determine their heating behavior—an estimation of the in vivo heating potential”, Nanoscale Research Letters, 2014, 10 pages, vol. 9. [cited by applicant]
Nazli et al., “RGDS-functionalized polyethylene glycol hydrogel-coated magnetic iron oxide nanoparticles enhance specific intracellular uptake by Hela cells”, International Journal of Nanomedicine, 2012, pp. 1903-1920, … [cited by applicant]
Palumbo et al., “Methods of Isolation, Characterization and Expansion of Human Adipose-Derived Stem Cells (ASCs): An Overview”, International Journal of Molecular Sciences, 2018, 13 pages, vol. 19. [cited by applicant]
Pislaru et al., “Magnetically Targeted Endothelial Cell Localization in Stented Vessels”, Journal of the American College of Cardiology, 2006, pp. 1839-1845, vol. 48:9. [cited by applicant]
Schlösser et al., “Mortality After Elective Abdominal Aortic Aneurysm Repair”, Annals of Surgery, Jan. 2010, pp. 158-164, vol. 251:1. [cited by applicant]
Sharma et al., “Experimental abdominal aortic aneurysm formation is mediated by IL-17 and attenuated by mesenchymal stem cell treatment”, Circulation, Sep. 2012, pp. S38-S45, vol. 126. [cited by applicant]
Siepe et al., “Stem cells used for cardiovascular tissue engineering”, European Journal of Cardio-Thoracic Surgery, 2008, pp. 242-247, vol. 34. [cited by applicant]
Tefft et al., “Magnetizable stent-grafts enable endothelial cell capture”, Journal of Magnetism and Magnetic Materials, 2017, pp. 100-104, vol. 427. [cited by applicant]
Turnbull et al., “Aortic Implantation of Mesenchymal Stem Cells after Aneurysm Injury in a Porcine Model”, J Surg Res., Sep. 2011, pp. e179-e188, vol. 170:1. [cited by applicant]