Granted Patent
B2
US 12,440,444 · App. 17/052,034 · Granted Oct 14, 2025
Matrix bound vesicles (MBVS) containing IL-33 and their use
Inventors:
Stephen Francis Badylak (West Lafayette, IN); George S. Hussey (Cranberry Township, PA); Heth Turnquist (Pittsburgh, PA); Jenna Lynn Dziki (Pittsburgh, PA); Quan Liu (Shenzhen, CN); Zhongqiang Zhang (Changsha, CN)
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Abstract
Methods are disclosed for treating a subject with a disorder, such as, but not limited to, a) fibrosis of an organ or tissue; b) solid organ transplant rejection; or c) a cardiac disease that is not myocardial infarction or myocardial ischemia. These methods include selecting a subject having or at risk of having the disorder, and administering to the subject a therapeutically effective amount of isolated nanovesicles derived from an extracellular matrix, wherein the nanovesicles contain interleukin (IL)-33 and comprise lysyl oxidase, and wherein the nanovesicles a) do not express CD63 or CD81, or b) are CD63 lo CD81 lo . In additional embodiments, methods are disclosed for increasing myoblast differentiation.
Claims (19)
1. A method for treating or inhibiting heart transplant rejection in a subject who has received a hear transplant comprising:
administering to the subject who has received a heart transplant a therapeutically effective amount of isolated nanovesicles derived from an extracellular matrix, wherein the nanovesicles comprise interleukin (IL)-33 and lysyl oxidase, and wherein the nanovesicles a) do not express CD63 or CD81, or b) are CD63 lo CD81 lo ,
thereby treating or inhibiting heart transplant rejection in the subject.
2. The method of claim 1 , wherein the extracellular matrix is a mammalian extracellular matrix.
3. The method of claim 2 , wherein the mammalian extracellular matrix is a pig, cow, or sheep extracellular matrix.
4. The method of claim 1 , wherein the extracellular matrix is from esophageal tissue, urinary bladder, small intestinal submucosa, dermis, umbilical cord, pericardium, cardiac tissue, or skeletal muscle.
5. The method of claim 1 , wherein the nanovesicles comprise miR-145 and/or miR-181.
6. The method of claim 1 , wherein the nanovesicles are administered to the transplanted heart of the subject.
7. The method of claim 1 , wherein the nanovesicles are administered intravenously.
8. The method of claim 1 , wherein the nanovesicles are administered weekly, bimonthly or monthly to the subject.
9. The method of claim 1 , further comprising administering to the subject an immunosuppressive agent, wherein the immunosuppressive agent is a calcineurin inhibitor, an antiproliferative agent, an mTOR inhibitor, and/or a steroid.
10. The method of claim 9 , wherein the calcineurin inhibitor is tacrolimus or cyclosporine; wherein the antiproliferative agent is mycophenolate; wherein the mTOR inhibitor is sirolimus, and/or wherein the steroid is prednisone, hydrocortisone, or cortisone.
11. The method of claim 1 , wherein the subject is a human.
12. The method of claim 3 , wherein the extracellular matrix is urinary bladder matrix (UBM).
13. The method of claim 3 , wherein the extracellular matrix is small intestinal submucosa (SIS) or dermis.
14. A method for treating or inhibiting chronic heart transplant rejection in a subject comprising:
administering to a subject who has received a heart transplant a therapeutically effective amount of isolated nanovesicles derived from a mammalian extracellular matrix, wherein the nanovesicles comprise interleukin (IL)-33 and lysyl oxidase, and wherein the nanovesicles a) do not express CD63 or CD81, or b) are CD63 lo CD81 lo ,
thereby treating or inhibiting chronic heart transplant rejection in the subject.
15. The method of claim 14 , wherein the method decreases monocyte-derived dendritic cells in the heart transplant in the subject.
Assignments (2)
CONFIRMATORY LICENSE
Recorded Oct 12, 2022
From: UNIVERSITY OF PITTSBURGH
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 061656/0791 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Oct 30, 2020
From: BADYLAK, STEPHEN FRANCIS; HUSSEY, GEORGE S.; TURNQUIST, HETH; DZIKI, JENNA LYNN; LIU, QUAN; ZHANG, ZHONGQIANG
To: UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION
Reel/Frame 054229/0950 →
Continuity (2)
Provisional Application
62666624
· May 3, 2018
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