Charles Lee

Bioheat and Mass Transfer Laboratory:

Research: Currently we are working in a number of research areas related to Biomedical Engineering

Hypothermic machine perfusion preservation of livers for transplantation:

With over 15,000 patients waiting for liver transplantation and over 1100 deaths a year as a result of organ shortages, there is a need to improve preservation of livers and new ways to expand the donor pool. Hypothermic machine perfusion (HMP) has the potential to provide better quality livers for transplant and reclaim marginal organs that currently are unusable. Currently, HMP has not improved long-term storage (>24 hrs) of livers and our group is investigating the cause of damage. Three subprojects related to this work are:

A.  Determining the effect of shear stress at hypothermic temperatures on endothelial cells in the isolated livers. Our group is able to machine perfused a liver on a temperature controlled microscope stage and image the sinusoidal structure of the liver with intravital microscopy.

B.  Understand the effect of shear stress on endothelial cells in a microshear chamber at hypothermic temperatures. Using primary cultures of liver endothelial cells we are using video microscopy to assess endothelial cell shape as a function of shear stress.

C.  Investigate the potential of reclaiming non-heart-beating donor livers with machine perfusion. Donors that experience cardiac arrest prior to removal of their organs experience periods of warm ischemia which make the organs unusable. Our group has shown that machine perfusion has the potential to reclaim and preserve for short periods these organs for transplant.

D.  Investigate the potential in preserving fatty livers by HMP.

E.  Collaboration with Carolinas Medical Center Transplantation Group and Organ Recovery Systems to scale-up HMP livers for transplants.

Bioinstrumentation:

Our group is finding that we need to build instruments for our research purposes and that these devices may have broader applications. We will continue to build such devices for diagnostics and imaging purposes.

Selected Publications:Pegg, D.E., Rubinsky, B., Diaper, M., Lee, C.Y. (1986) Analysis of the introduction and removal of glycerol in rabbit kidney using a Krogh cylinder model, Cryobiology, 23, 150-160.

Rubinsky, B., Lee, C.Y., Bastacky J., and Hayes, T.L., (1987), The mechanism of freezing in biological tissue:  the liver, Cryo-Letters, 8: 370-381.

C.Y. Lee and B. Rubinsky, “Multidimensional Analysis of Momentum and Mass Transfer in the Hepatic Acinus,” in Computational Methods in Bioengineering, R.L. Spilker and B.R. Simon Eds., ASME Press, NY, NY, 1988, pp. 267-280 (Invited).

Lee, C.Y. and Rubinsky, B., (1989) A multi-dimensional model of momentum and mass transfer in the liver, Int. J. Heat and Mass Transfer 32: 2421-2434

Lee, C.Y., Rubinsky, B., and Fletcher, G.L., (1992) Hypothermic preservation of whole mammalian organs with “antifreeze” proteins, Cryo-Letter, 8: 190-198.

Rubinsky B., Arav A., Hong J.S., and Lee C.Y., (1994) Freezing of mammalian livers with glycerol and antifreeze proteins, Biochemical and Biophysical Research Communications, 200 (2): 732-41.

Lee, C.Y., Matsumoto-Pon, J., and Widdicombe, J.H., (1997) Cultured lung epithelium: cellular model for lung preservation, Cryobiology 35: 209-218.

Ishine, N., Rubinsky, B., and Lee, C.Y., (1999) A histological analysis of liver injury in freezing storage, Cryobiology, 39 (4): 271-277.

Ishine, N., Rubinsky, B., and Lee, C.Y., (2000) Transplantation of mammalian livers after freezing: vascular damage and functional recovery, Cryobiology, 40: 84-89.

Lee, C.Y., Zhang, J.X., deSilva, H., Coger, R.N., and Clemens, M.G., (2000) Heterogeneous flow patterns during hypothermic machine perfusion preservation of livers Transplantation 70: 1797-1802.

Purohit, S., Nelson, J., Zhang, J.X., Clemens, M.G., and Lee, C.Y. (2001) Flow dynamics during machine perfusion preservation of livers for transplantation, Proceedings of the 2001 International Mechanical Engineering Congress and Exposition.

Venkatapathi, M., and Lee, C.Y., (2001) Portable fluorometry for kinetics application, Proceedings of the 2001 International Mechanical Engineering Congress and Exposition.

Lee, C.Y., Zhang, J.X., Jones, J.W. Jr., Southard, J.H., Clemens, M.G., (2002) Functional recovery of preserved livers following warm ischemia:  Improvements by machine perfusion preservation, Transplantation, 74(7): 944-951.

Slater, J.H., Jain, S, Coger, R.N., and Lee, C.Y., (2002) The effect of shear stress on endothelial cells at hypothermic temperature, Proceedings of the 2002 International Mechanical Engineering Congress and Exposition.

Lee, C. Y., Jain, S, Duncan, H. M., Zhang, J.X., Jones, J.W.Jr, Southard, J.H., Clemens, M.G. (2003) Survival transplantation of non-heart-beating donor rat livers following hypothermic machine perfusion preservation, Transplantation 76 (10) pp. 1432-36.

Hongzhi Xu, Charles Y. Lee^,, Mark G. Clemens, Jian X. Zhang, (2004) Prolonged Hypothermic Machine Perfusion Preserves Hepatocellular Function but Potentiates Endothelial Cell Dysfunction in Rat Livers, Transplantation 77:11, pp 1676-82.

Jain, S., Purohit, S., Xu, H., J.X. Zhang, Clemens, M.G., and Lee, C.Y. (2004) Ex vivo study of flow dynamics and endothelial cell structure during extended hypothermic machine perfusion preservation of livers, Cryobiology 48, pp. 322-332.

Xu, H, Zhang, J.X., Jones, J.W.Jr, Southard, J.H., Clemens, M.G., Lee, C.Y., Hypothermic Machine Perfusion of Rat Livers Preserves Endothelial Cell Function, presented at the 20^th International Congress of the Transplant Society and to appear in Transplantation Proceedings.

S.Jain, C.Y.Lee, S.Baicu, H.Duncan, H.Xu, J.W.Jones Jr, M.G.Clemens, J.Brassil, M.J.Taylor, K.G.M.Brockbank, (2004) Hepatic Function in Hypothermically Stored Porcine Livers: Comparison of Hypothermic Machine Perfusion vs. Cold Storage, presented at the 20^th International Congress of the Transplant Society and to appear in Transplantation Proceedings.

Funding:

The Whitaker Foundation Biomedical Engineering Research Grant

National Institutes of Health’s Bioengineering Research Partnership Award