Publications

Feasibility Studies of Percutaneous Mammalian Cell Delivery for Local Myocardial Treatment

M. Rezaee, P. Altman, J.D. Altman, T. Quertermous, A.C. Yeung, A. Carter, S. Stertzer

Stanford Cardiovascular Medicine, Stanford, California, BioCardia, Inc., South San Francisco, California, Mayo Clinic Foundation, Rochester, Minnesota

Background: Mammalian cell transplantation for in-vivo tissue engineering has been applied to treat diabetes. However results of cellular grafting experiments for myocardial treatment have been limited, at least in part, due to lack of efficacious delivery modality. Intramyocardial delivery (IMD) is currently under investigation for local delivery of various reagents including growth factors to promote angiogenesis. With this approach, there is potential for local delivery of high concentration of reagents within the myocardial interstitium. For the purpose of this study, we have developed a unique Percutaneous delivery system for IMD. This system utilizes an infusion system that allows stable engagement into the myocardium, with the abilitry to regulate the rate of delivery, while reducing the possibility of myocardial damage. This system was applied to determine the feasibility of percutaneous mammalian cell transplantation for in-vivo tissue engineering.

Methods: The pattern of delivery within the myocardial interstitium was first determined by delivery of 15 um fluorescent microspheres. After the deliveries, the animals (porcine, n=3) were sacrificed and microsphere localization was examined within semi thin sections of myocardium. Feasibility of the catheter to deliver mammalian cells was first determined in vitro by determining the viability of vascular smooth muscle cells which were injected through the anchoring infusion system. Subsequently, intramyocardial cell transplantation was performed by delivery of 1x10^6 porcine skeletal muscle cells in a volume of 0.5ml through the infusion catheter (n=5). The histological distribution of the transplanted cells was determined either acutely (n=3) or after 3 weeks (n=2).

Results: Histological examination of the sites of fluorescent microspheres demonstrated distribution of particles within the myocardial interstitium, around the sites of IMD. Cell delivery experiments demonstrated that cells remain viable after injection through the infusion catheter , three hours after delivery, the injected cells occupy a volume of approximately 1-2cm^3 within the region of myocardial delivery. At 3 weeks after delivery, the fraction of viable transplanted cells appears to be incorporated within the myocardial architecture with some inflammatory reaction around the injection sites.

Conclusions: These studies demonstrate the feasibility of this Percutaneous system to deliver mammalian cells for local and regional treatment.

Am. J. Cardiol 2000; 86(suppl 8A): 4i.