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Animal models - George E Georges, Brenda M Sandrnaier and Rainer Storb CONTENTS . lntroduction Stem cells circulate in peripheral blood . Stern cell characterization . In vitro assays for stem cells . Stern cell phenotype Mobilization of stem cells Cytokine-mobilized stem cells - Murine stem cell mobilization Large animals . Graii-versus-host disease and blood stem cell transplantation Summary Significant progress has been made in the past fe~v years in the development of blood stem cell transplantation as a method for treatment of patients with hematologic and non-hematologic malignancies. Work using animal models has helped Set the stage for these developments. This chapter will highlight the background his- tory and recent progress of that work. The primary aiiimal models include inbred mice and rats and random-bred dogs, rabbits and non-human primates. The need for animal models is clear: there are macceptable risks to patients when clinically untested modifications are made to transplant protocols. Animal mod- els serve as the means with which to reliably assess the biology and the likely outcome of nerv approaches to stem celi transplantation. 111 general, the inbred mouse has been a oery use- ful model for studying the basic biology of hematopoiesis, as well as for providuig rapid readouts for studying basic principles of trans- plantation. The major caveat with the murine I Table 1.1 Red blood cell demands of different species' I RBC per rni Weight Biood volurne RBC life span RBC Life expectancy RBC per life Species (X 10') (kg) iml) idays) per day iyears) of animal Mouse 9.0 0.025 1.8 50 3.2 X 10' 2 2.4 X 10" Human 6.0 70 4900 120 2.5 X 10" 80 7.3 X 1OX5 Cat 7.5 4 280 70 3.0 X IO'O 15 1.6 X l0l4 Dog 7.2 18 1550 115 9.7 X 10'O 13 4.6 X 1014 'Adapted from Abkowitz et al.5'

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Animal models -

George E Georges, Brenda M Sandrnaier and Rainer Storb

CONTENTS . lntroduction Stem cells circulate in peripheral blood . Stern cell characterization . In vitro assays for stem cells . Stern cell phenotype Mobilization of stem cells Cytokine-mobilized

stem cells - Murine stem cell mobilization Large animals . Graii-versus-host disease and blood stem cell transplantation Summary

Significant progress has been made in the past f e~v years in the development of blood stem cell transplantation as a method for treatment of patients with hematologic and non-hematologic malignancies. Work using animal models has helped Set the stage for these developments. This chapter will highlight the background his- tory and recent progress of that work.

The primary aiiimal models include inbred mice and rats and random-bred dogs, rabbits

and non-human primates. The need for animal models is clear: there are macceptable risks to patients when clinically untested modifications are made to transplant protocols. Animal mod- els serve as the means with which to reliably assess the biology and the likely outcome of nerv approaches to stem celi transplantation. 111 general, the inbred mouse has been a oery use- ful model for studying the basic biology of hematopoiesis, as well as for providuig rapid readouts for studying basic principles of trans- plantation. The major caveat with the murine

I Table 1.1 Red blood cell demands of different species' I RBC per rni Weight Biood volurne RBC life span RBC Life expectancy RBC per life

Species (X 10') (kg) iml) idays) per day iyears) of animal

Mouse 9.0 0.025 1.8 50 3.2 X 10' 2 2.4 X 10"

Human 6.0 70 4900 120 2.5 X 10" 80 7.3 X 1OX5

Cat 7.5 4 280 70 3.0 X I O ' O 15 1.6 X l 0 l 4

Dog 7.2 18 1550 115 9.7 X 10'O 13 4.6 X 1014

'Adapted from Abkowitz et al.5'

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