IP Library Granted Patent US 10,851,347
Granted Patent B2
US 10,851,347 · App. 16/307,015 · Granted Dec 1, 2020

Altered adherent stromal cells and methods of producing and using same

Inventors: Eytan Abraham (Frederick, MD); Lior Raviv (Kfar-Monash, IL); Maya Wadamany (Haifa, IL); Nadav Eshkol (Haifa, IL)
Assignee: PLURISTEM LTD.
C12N5/0668A61K35/12A61K35/50C12M21/00C12M23/14C12N2501/052C12N2501/24C12N2501/25C12N2513/00C12N2533/30
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Quick Facts
Patent No.
US 10,851,347
App. No.
16/307,015
Granted
Dec 1, 2020
Kind
B2
Abstract

Disclosed herein are altered adherent stromal cells and methods of producing and utilizing same.

Claims (25)

1. A method of increasing CCL5 secretion from adherent stromal cells (ASC), said method comprising the step of incubating ASC from placental or adipose tissue in a three-dimensional (3D) culture in a cytokine-containing growth medium, wherein one or more cytokines have been added to said cytokine-containing growth medium, wherein:

said one or more cytokines comprise Tumor Necrosis Factor alpha (TNF-alpha), wherein the TNF-alpha is present at a concentration between 1-12 nanograms/milliliter,

said 3D culture is performed in a bioreactor, and

incubating said ASC in said cytokine-containing growth medium is commenced during exponential phase,

thereby increasing CCL5 secretion from ASC.

2. The method of claim 1 , said method comprising the steps of: (a) incubating said ASC from placental or adipose tissue in a 3D culture in a first growth medium, wherein no pro-inflammatory cytokines have been added to said first growth medium; and (b) subsequently performing the step of incubating said ASC in said cytokine-containing growth medium.

3. The method of claim 1 , further comprising the subsequent step of harvesting said ASC by removing said ASC from said 3D culture.

4. The method of claim 1 , wherein said 3D culture comprises a synthetic adherent material.

5. The method of claim 1 , wherein the step of incubating said ASC in said cytokine-containing growth medium comprises: (i) adding a bolus of said TNF-alpha to a medium in said bioreactor, thereby generating said cytokine-containing growth medium; and (ii) operably connecting said cytokine-containing growth medium with an external reservoir comprising an additional amount of said TNF-alpha.

6. The method of claim 1 , wherein said cytokine-containing growth medium further comprises Interferon-Gamma (IFN-gamma).

7. The method of claim 6 , wherein said IFN-gamma is present at a concentration between 1-12 nanograms/milliliter.

8. The method of claim 1 , wherein said ASC originate from placenta tissue.

9. The method of claim 1 , wherein said ASC originate from adipose tissue.

10. ASC produced by the method of claim 1 .

11. A population of cells, wherein the majority of said population expresses, on a population level, each of CD10, CD29, CD38, and CD40.

12. A population of cells, wherein the majority of said population expresses, on a population level, each of CD10, CD29, HLA-DR, and CD74.

13. The population of cells of claim 11 , wherein said population is at least 40% positive for at least one of a marker selected from: CD42a, CD45Ra, CD77, CD243, and CD275.

14. A pharmaceutical composition comprising the ASC of claim 10 .

15. A bioreactor comprising the ASC of claim 10 .

16. The population of cells of claim 11 , wherein the majority of said population further expresses CD90.

17. A pharmaceutical composition comprising the population of cells of claim 11 .

18. A bioreactor comprising the population of cells of claim 11 .

19. The population of cells of claim 12 , wherein the majority of said population further expresses CD90.

20. A pharmaceutical composition comprising the population of cells of claim 12 .

21. A bioreactor comprising the population of cells of claim 12 .

Assignments (2)
CHANGE OF NAME Recorded Dec 30, 2022
From: PLURISTEM LTD.
To: PLURI BIOTECH LTD.
Reel/Frame 062247/0037 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 19, 2018
From: ABRAHAM, EYTAN; RAVIV, LIOR; WADAMANY, MAYA; ESHKOL, NADAV
To: PLURISTEM LTD.
Reel/Frame 047819/0272 →
Continuity (1)
Related Publication 20200131481A1 · Apr 30, 2020