Cardiac cells implanted into a cylindrical, vascularized chamber in vivo: pressure generation and morphology.
We have previously described a model to implant dissociated cells into a cylindrical, vascularized bed in vivo to promote the formation of functional cardiac muscle constructs. We now investigate the cellular organization and the ability of the constructs to generate intra-luminal pressure. Primary cardiac cells were isolated from hearts of 2-3 day old rats, suspended in fibrin gel and inserted into the lumen of silicone tubing. The silicone tubing was then implanted around the femoral vessels in the groin region of recipient animals. After 3 weeks, the constructs were harvested, placed in an in vitro bath and cannulated via the incorporated femoral artery with a pressure transducer for evaluation of intra-luminal pressure dynamics. Histological evaluation showed the presence of a concentric ring of cardiac cells surrounding the femoral vessels. There was also a significant amount of collagen present around cardiac cells. In addition, we observed a significant amount of neovascularization of the explanted constructs. Electron microscopy showed the presence of longitudinally aligned fibers with a large number of gap junctions. Upon electrical stimulation of a single pulse (7 V, 1.2 ms), the constructs generated an intra-luminal pressure of 1.19 +/- 0.45 mmHg (n = 6). In addition, we were able to electrically pace the constructs at frequencies of 0.5-5 Hz. A Starling behavior of the inverse relation between baseline pressure and twitch pressure was observed. Cardiac cells implanted for 3 weeks into the cylindrical vascularized bed formed a tissue construct that demonstrated many of the contractile properties and morphology expected of functioning cardiac tissues.
Birla
Ravi K
RK
Section of Cardiac Surgery, University of Michigan, MSRB I, A510E, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA. rbirla@umich.edu
Dhawan
Vikas
V
Dow
Douglas E
DE
Huang
Yen-Chih
YC
Brown
David L
DL
D000818:Animals; D000831:Animals, Newborn; D021522:Bioartificial Organs; D001794:Blood Pressure / Q000502:physiology; D002478:Cells, Cultured; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006354:Heart, Artificial; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology* / Q000637:transplantation*; D009924:Organ Culture Techniques / Q000295:instrumentation* / Q000379:methods; D010477:Perfusion / Q000295:instrumentation* / Q000379:methods; D051381:Rats; D011916:Rats, Inbred F344; D023822:Tissue Engineering / Q000295:instrumentation* / Q000379:methods