Evidence that rehydrated, lyophilized red blood cells are sufficiently deformable for normal microcirculation transit

Evidence that rehydrated, lyophilized red blood cells are sufficiently deformable for normal microcirculation transit
Published Online: 29 Nov 2004
Received: 2 June 2004; Accepted: 27 July 2004
Thomas H. Fischer 1 *, Mary E. Robbins 2, Arthur P. Bode 3, Timothy C. Nichols 1, Dwight E. Bellinger 1, Mark H. Schoenfisch 2
Microscopy Research and Technique
Volume 65, Issue 1-2 , Pages 62 - 71
Special Issue: Anatomy and Function of the Nervus Terminalis - Part I . Issue Edited by Celeste Wirsig-Wiechmann.
Wiley InterScience
1Department of Pathology and Laboratory Medicine, Francis Owen Blood Research Laboratory, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
2Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
3Department of Pathology and Laboratory Medicine, East Carolina School of Medicine, Greenville, North Carolina

email: Thomas H. Fischer (tfischer@med.unc.edu)
*Correspondence to Thomas H. Fischer, Department of Pathology and Laboratory Medicine, Francis Owen Blood Research Laboratory, 350 S. Old Fayetteville Rd., University of North Carolina at Chapel Hill, Chapel Hill, NC 27516
Two of the authors (T.H.F and A.P.B) have declared a financial interest in a company whose product was studied in the present work.
Funded by:
Navy Medical Research and Development Command; Grant Number: N00014-97-0867, N00014-97-0891
National Science Foundation
Keywords
red blood cell ? deformability ? atomic force microscopy ? intravital microscopy ? lyophilize
Abstract
A method was developed for the preparation of rehydratable lyophilized red blood cells (RL RBCs) that hold promise as cell-based oxygen carriers for transfusion medicine. The maintenance of normal cellular deformability is essential for the successful development of cell-based oxygen delivery systems. Improper deformability of RBCs can lead to hemolysis if too fragile or microvascular occlusion if too rigid. We developed an aldehyde stabilization method that is based on the use of paraformaldehyde polymers that complement the function of spectrin as a structural unit with conformational flexibility. Three types of in vitro deformability studies (filter transit, pipette aspiration, and atomic force microscopy) and in vivo intravital microscopy were performed to characterize the deformability of RL RBCs. When considered with safety data from previously reported studies in dogs, the results of these studies indicate that paraformaldehyde-modified RL RBCs have visco-elastic deformability properties that are in the nonpathological range. Microsc. Res. Tech. 65:62-71, 2004. ? 2004 Wiley-Liss, Inc.