Open AccessEvaluation of Stem Cell-Derived Red Blood Cells as a Transfusion Product Using a Novel Animal Model
Author(s) -
Sandeep N. Shah,
Monique P. Gelderman,
Emily M.A. Lewis,
John Farrel,
Francine Wood,
Michael Brad Strader,
Abdu I. Alayash,
Jaroslav G. Vostal
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0166657
Subject(s) - stem cell , ex vivo , in vivo , cord blood , red blood cell , blood product , immunology , cd34 , blood cell , biology , microbiology and biotechnology , andrology , chemistry , medicine , pathology
Reliance on volunteer blood donors can lead to transfusion product shortages, and current liquid storage of red blood cells (RBCs) is associated with biochemical changes over time, known as ‘the storage lesion’. Thus, there is a need for alternative sources of transfusable RBCs to supplement conventional blood donations. Extracorporeal production of stem cell-derived RBCs (stemRBCs) is a potential and yet untapped source of fresh, transfusable RBCs. A number of groups have attempted RBC differentiation from CD34 + cells. However, it is still unclear whether these stemRBCs could eventually be effective substitutes for traditional RBCs due to potential differences in oxygen carrying capacity, viability, deformability, and other critical parameters. We have generated ex vivo stemRBCs from primary human cord blood CD34 + cells and compared them to donor-derived RBCs based on a number of in vitro parameters. In vivo , we assessed stemRBC circulation kinetics in an animal model of transfusion and oxygen delivery in a mouse model of exercise performance. Our novel, chronically anemic, SCID mouse model can evaluate the potential of stemRBCs to deliver oxygen to tissues (muscle) under resting and exercise-induced hypoxic conditions. Based on our data, stem cell-derived RBCs have a similar biochemical profile compared to donor-derived RBCs. While certain key differences remain between donor-derived RBCs and stemRBCs, the ability of stemRBCs to deliver oxygen in a living organism provides support for further development as a transfusion product.