1. Growing Cardiovascular Tissues In Vitro
Rich Goodwin, PhD
Cell Biology and Anatomy
USC School of Medicine

5. A. C.
Lumen
B.
B. D.
D.
C.

6. Day 21 Cardiotube

7. Embryonic Mouse Cardiac Myocytes at 11 Days of Culture

8. TEMs of Tube Cultured Cardiac Myocytes
Undergo myofibrillogenesis and development cell‐cell juncMons
Evans et al, 2003

9. We are using cardiotubes to test mechanisms of cardiovascular development
such as Tetralogy of Fallot (Dr. Kheradvar).
Toxicity Screening (Dr. Yost/Biotech)

10. *
*
1 2 3

11. Stage 25 AV cushions in lumen of tube scaffold
Day 2

12. The All New and Improved
FLOWMASTER 3000!!!
(John Weidner, USC)

13. Free Edge

14. Tenascin C expression and localizaMon regulated by Flow and RhoA
Hong Tan

15. Flow and RhoA can regulate the material properMes of
developing valves as measured by Atomic Force Microscopy
14001
No Flow Flow Flow w/ LPA Flow w/ y‐compound
60 12001
Young's Modulus (Pa)
50 10001
40 8001
Force (nN)
30 6001
20 4001
10 2001
0 1
0 500 1000 1500 2000 2500 3000 No Flow Flow Flow w/ y‐compound Flow w/ LPA
z (nm)
Hong Tan, Stef Biechler, (P<0.05)
and Dr. Dean (Clemson)

16. Valve Conclusions
• Expression of Fibrous ECM proteins can be
regulated by flow.
• We hypothesize that the mechanical forces
created by pulsaVle flow deform the
cytoskeleton and acVvate the RhoA pathway.
• Experimental manipulaVon of the RhoA
pathway does regulate Fibrous ECM expression
and localizaVon in developing valves
So, if you want to make stronger valves faster, use Flow and RhoA

17. Coronary Development

22. Many Thanks:
JD Pods and MJ Yost ‐ USC SOM
Bob Price ‐ USC IRF
My Lab
HJ Evans‐Anderson – Alumnus
Stefanie Biechler
Lorain Junor MUSC
Andrea Roberts Roger Markwald
Samantha SMnson Chip Norris
Hong Tan
USC Engineering Northwestern:
John Weidner, Arash Kheradvar Bob Dedman
Clemson:
NIH Support Delphin Dean
Cobre P20‐RR1634 (RRM)
R21 HL080294 (RLG)
RO1 HL086856 (RLG)
NSF RII Bridge A. Tsiaras In Life Aug. 26th, 2005

23. Key Points:
• The mechanisms of cardiovascular development can invesMgated using 3D
culturing techniques.
• Developmental mechanisms are likely to be important during regeneraMon.
Problems:
• The transiMon from capillary to larger caliber blood vessels has been
difficult to model.
• Numerous others.
CollaboraMons:
• Clinical applicaMons.
• Grateful for my present collaborators