US 12,291,725 B2
Systems and methods for producing injectable enhanced stem cell exosomes, improved exosomes and methods of use
Sharan Ramaswamy, Miami, FL (US); Manuel Perez, Miami, FL (US); and Yih-Mei Lin, Miami, FL (US)
Assigned to The Florida International University Board of Trustees, Miami, FL (US)
Filed by Sharan Ramaswamy, Miami, FL (US); Manuel Perez, Miami, FL (US); and Yih-Mei Lin, Miami, FL (US)
Filed on Jul. 12, 2023, as Appl. No. 18/221,026.
Application 18/221,026 is a division of application No. 17/119,170, filed on Dec. 11, 2020, granted, now 11,746,329.
Claims priority of provisional application 62/947,379, filed on Dec. 12, 2019.
Prior Publication US 2023/0348860 A1, Nov. 2, 2023
Int. Cl. C12N 5/0775 (2010.01); A61K 9/00 (2006.01); A61K 35/28 (2015.01); A61P 9/10 (2006.01); C07K 14/47 (2006.01); C07K 14/765 (2006.01)
CPC C12N 5/0663 (2013.01) [A61K 9/0019 (2013.01); A61K 35/28 (2013.01); A61P 9/10 (2018.01); C07K 14/47 (2013.01); C07K 14/4717 (2013.01); C07K 14/765 (2013.01); C12N 2521/00 (2013.01); C12N 2533/40 (2013.01); C12N 2533/92 (2013.01)] 5 Claims
 
1. Injectable enhanced stem cell exosomes (IESCE) secreted from stem cells, the IESCE being produced by a method comprising seeding stem cells onto a bio-scaffold; subjecting the stem cells on the bio-scaffold to rotisserie culture for ≥8 days; placing the bio-scaffold in a bioreactor that delivers a physiological oscillatory flow condition to the stem cells on the bio-scaffold; culturing the stem cells in a culture medium in the bioreactor under the physiological oscillatory flow condition for ≥14 days; collecting IESCEs from the culture medium; and measuring a level of fibronectin in IESCEs, wherein the level of fibronectin in the IESCE is at least 50% lower as compared to those of static culture; the stem cells being bone marrow mesenchymal stem cells (BMSCs); and the IESCE comprising at least one tissue repair factor selected from interleukin-6 (IL-6), interleukin-10 (IL-10), extracellular matrix metalloproteinase inducer (EMMPRIN), matrix metalloproteinase (MMP)-9, and granulocyte colony stimulating factor (G-CSF), and the IESCEs further comprising no alpha-2-macroglobulin.