Composition and method to improve the therapeutic effect of stem cells
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 + 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 + cells and then a co-culture of a CD34 + cells with CD34 + -derived endothelial cells within a biomimetic gel.
1. A composition comprising a co-culture of:
a) a population of CD34 + hematopoietic stem cells derived from human umbilical cord blood; and
b) a population of CD34 + endothelial cells derived from said CD34 + hematopoietic stem cells, wherein a) and b) are encapsulated in a fibrin gel and
wherein the ratio of said CD34 + hematopoietic stem cells to said CD34 + 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 + hematopoietic stem cells comprises autologous cells, allogeneic cells or a mixture thereof.
6. The composition according to claim 1 , comprising CD34 + hematopoietic stem cells in a concentration from 10×10 2 to 10×10 6 cells per 1 mL of fibrin gel, wherein the ratio of CD34 + hematopoietic stem cells to CD34 + endothelial cells is between 10:1 and 5:1.
7. The composition according to claim 1 , wherein the CD34 + hematopoietic stem cells are present in a concentration of 4.0×10 6 cells per 1 mL of a fibrin gel.
8. The composition according to claim 1 , wherein the ratio of CD34 + hematopoietic stem cells to CD34 + endothelial cells is between 0.5:1 and 3:1.
9. The composition according to claim 1 , further comprising VEGF 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 165 , PDGF, angiopoietin-Ang, ephrin-Eph, fibroblast growth factor-FGF, placental growth factor-PIGF, transforming growth factor β-1 (TGF-β1), 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 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.