Therapy using cardiac stem cells and mesenchymal stem cells
Compositions comprising stem cells delivered into infarcted myocardium by endocardial injection, engraft and differentiate into myocytes, endothelial cells, and vascular smooth muscle, and do so without the requirement for survival enhancing modification. These cells engraft whether injected acutely (days) or late (months) after myocardial infarction, and the efficiency of engraftment correlates with the functional recovery of the heart. The stem cells also recruit endogenous cardiac precursor cells, reconstitute myocardial stem cell niches, and enhance endogenous cell differentiation into myocytes.
1. A method of treating heart disease in a patient comprising:
mixing ex vivo mesenchymal stem cells with c-kit pos cardiac stem cells; and
administering to the patient's cardiac tissue in vivo the mixture of mesenchymal stem cells and cardiac stem cells in a concentration effective to repair damaged cardiac tissue.
2. The method of claim 1 , wherein the mesenchymal stem cells are allogenic to the patient.
3. The method of claim 1 , wherein the administration of the mixture increases ejection fraction of the patient's heart.
4. The method of claim 1 , wherein the mesenchymal stem cells are autologous to the patient.
5. The method of claim 1 , wherein the cardiac stem cells are identified by at least one marker comprising cardiac transcription factor GATA-4; endothelial cell markers Factor VIII and KDR; vascular smooth muscle marker α-smooth muscle actin; or cardiomyocyte marker α-sarcomeric actinin.
6. The method of claim 1 , wherein the mesenchymal stem cells are obtained from bone marrow, tissues, or organs.
7. The method of claim 1 , wherein the mesenchymal stem cells are from adult bone marrow cells.
8. The method of claim 1 , wherein the cardiac stem cells are additionally identified by as being connexin-43 positive, N-cadherin positive, CD3neg, CD14neg or CD68neg.