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Last Updated: March 29, 2024

Claims for Patent: 9,855,300


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Summary for Patent: 9,855,300
Title:Composition and method to improve the therapeutic effect of stem cells
Abstract: The invention relates to a composition and method used for injuries treatment with a surprisingly therapeutic effect. This composition comprises a population of cells derived from human umbilical cord blood which expresses one of the following markers: CD34, CD45, and CD31; a population of CD34.sup.+ derived endothelial cells; and a biomimetic gel, preferably fibrin. The method for obtaining the composition comprises the derivation of a population of endothelial cells from CD34.sup.+ cells and then a co-culture of a CD34.sup.+ cells with CD34.sup.+-derived endothelial cells within a biomimetic gel.
Inventor(s): Da Silva Ferreira; Lino (Coimbra, PT), Dos Santos Pedroso; Dora Cristina (Benavente, PT)
Assignee: CRIOESTAMINAL, SA DE E TECNOLOGIA, SA. (Cantanhede, PT)
Application Number:13/989,708
Patent Claims:1. A composition comprising a co-culture of: a) a population of CD34.sup.+ hematopoietic stem cells derived from human umbilical cord blood; and b) a population of CD34.sup.+ endothelial cells derived from said CD34.sup.+ hematopoietic stem cells, wherein a) and b) are encapsulated in a fibrin gel and wherein the ratio of said CD34.sup.+ hematopoietic stem cells to said CD34.sup.+ endothelial cells is between 0.5:1 and 10:1 and wherein the co-culture secretes IL-10 and IL-17.

2. The composition according to claim 1 further comprising an excipient.

3. The composition according to claim 1, wherein the fibrin gel is prepared by crosslinking fibrinogen in the presence of thrombin, and wherein the fibrin gel comprises fibrinogen at a concentration from 1-100 mg/ml and thrombin at a concentration from 1-500 U/ml.

4. The composition according to claim 3, wherein the fibrin gel comprises fibrinogen at a concentration from 10-30 mg/ml and thrombin at a concentration from 2-50 U/ml.

5. The composition according to claim 1, wherein the population of the CD34.sup.+ hematopoietic stem cells comprises autologous cells, allogeneic cells or a mixture thereof.

6. The composition according to claim 1, comprising CD34.sup.+ hematopoietic stem cells in a concentration from 10.times.10.sup.2 to 10.times.10.sup.6 cells per 1 mL of fibrin gel, wherein the ratio of CD34.sup.+ hematopoietic stem cells to CD34.sup.+ endothelial cells is between 10:1 and 5:1.

7. The composition according to claim 1, wherein the CD34.sup.+ hematopoietic stem cells are present in a concentration of 4.0.times.10.sup.6 cells per 1 mL of a fibrin gel.

8. The composition according to claim 1, wherein the ratio of CD34.sup.+ hematopoietic stem cells to CD34.sup.+ endothelial cells is between 0.5:1 and 3:1.

9. The composition according to claim 1, further comprising VEGF.sub.165 at a concentration in the range of about 30 ng/mL to 100 ng/mL.

10. The composition according to claim 1 further comprising any of collagen I, collagen IV, laminin, fibrin, fibronectin, a proteoglycan, a glycoprotein, a glycoaminoglycan, a proteinase, a collagenase, a chemotactic agent, or a growth factor.

11. The composition according to claim 10, comprising a growth factor selected from the group consisting of: VEGF, VEGF.sub.165, PDGF, angiopoietin-Ang, ephrin-Eph, fibroblast growth factor-FGF, placental growth factor-PIGF, transforming growth factor .beta.-1 (TGF-.beta.1), cytokines, erythropoietin, thrombopoietin, transferring, insulin, stem cell factor (SCF), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF) and any mixture of any of the foregoing.

12. The composition according to claim 9, wherein the concentration of VEGF.sub.165 is 50 ng/mL.

13. The composition according to claim 1, wherein the fibrin gel comprises a concentration of Fetal Bovine Serum (FBS) between 15% and 20% (v/v).

14. The composition according to claim 1, wherein the composition is in the form of a topical formulation or an injectable formulation.

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