Table Of ContentHandbook of the Hemopoietic
Microenvironment
Contemporary Biomedicine
Handbook of the Hemopoietic Microevironment
Edited by Mehdi Tavassoli, 1989
The Red Cell Membrane
Edited by B. U. Raess and Godfrey Tunnicliff, 1989
Leukolysins and Cancer
Edited by Janet H. Ransom and John R. Ortaldo,
1988
Methods of Hybridoma Formation
Edited by Arie H. Bartal and Yashar Hirshaut,
1987
Monoclonal Antibodies in Cancer
Edited by Stewart Sell and Ralph A. Reisfeld, 1985
Calcium and Contractility: Smooth Muscle
Edited by A. K. Grover and E. E. Daniel, 1984
Carcinogenesis and Mutagenesis Testing
Edited by J. F. Douglas, 1984
The Human Teratomas: Experimental and Clinical
Biology
Edited by Ivan Damjanov, Barbara B. Knowles,
and Davor Solter, 1983
Human Cancer Markers
Edited by Stewart Sell and Britta Wahren, 1982
Cancer Markers: Diagnostic and Developmental
Significance
Edited by Stewart Sell, 1980
Handbook
of the
Hemopoietic
Microenvironment
Edited by
Mehdi Tavassoli
Humana Press
Clifton, New Jersey
o Copyright 1989 by The Humana Press Inc.
Softoover reprint of the hardcover 1s t edition 1989
Crescent Manor
PO Box 2148
Clifton, NJ 07015
All rights of any nature whatsoever reserved.
No part of this book may be reproduced, storedin a retrieval sytem, or transmitted in any form
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mission from the publisher.
Library of Congress Cataloging-in-Publication Data
Handbook of the Hemopoietic Microenvironment/edited. by Mehdi Tavassoli
p. 453 cm.-{Contcmporary biomedicine)
Indudes bibliographies and index.
ISBN-13: 978-1-4612-8845-9 e-ISBN-13: 978-1-4612-4494-3
001: 10.1007/978-1-4612-4494-3
1. Hematopoiesis I. Tavassoli, Mehdi, 1933- . II. Series
IDNLM: 1. Bone marrow-cytology. 2. Bone marrow-physiology.
3. Hematopoiesis. 4. Hematopoietic System--cytology.
5. Hematopoietic System-physiology. WH 140 H236]
QP92.H36 1989
612.4'91-dc20
DNLM/DLC
for Ubrary of Congress 89-15497
CIP
Preface
In 1868, Ernst Neumann recognized that blood cells re
quire continuous replenishment during postnata1life. Before
him, the assumption was that cells of the blood, like nerves
once formed in the embryo, remain in the body throughout
life. Neumann also recognized that this process occurred
within the bone marrow, because this tissue provided a fa
vorable environment for proliferation and differentiation of
blood cell precursors.
Vera Danchakoff, the Russian embryologist working in
the US, in 1916 made an analogy to the soil and the seed. Bone
marrow forms the soil, providing a favorable environment
for the growth of seed, the hemopoietic stem cell, and other
progenitor cells.
Imagine in the remote past a heap of similar tree seeds.
These seeds develop in our moderate climate into a tall
and many branched tree. Suppose the wind bears a part
of the seeds away and brings them to a land possessing
different environmental conditions, we will say the arc
tic lands. There the seeds may develop but they may pro
duce trees no higher than our moss.
Some 50 years later, the advent of bone marrow trans
plantation techniques proved her to be correct: in 1961, Till
and McCulloch developed their celebrated spleen colony
technique, and shortly after, Trentin and coworkers found
that the difference in the differentiation pathways of these
colonies is determined by the differences in the environ
mental "niches" in the stroma of hemopoietic tissues. Simul-
v
Preface
VI
taneously, many other techniques were used to gain further
insight into cellular components of stroma and extracellular
matrix and the nature of their interactions with hemopoietic
stems cells and progenitor cells.
A quarter of a century has passed since this area of re
search opened, and it has now blossomed. Yet, surprisingly,
no volume has been devoted to a synthesis of this field. In this
volume, which is devoted to the treatment of "soil," some of
the leading authorities in the field have undertaken this
synthesis. John Trentin provides a historical perspective, as
well as a definition. He critically reviews the evidence for the
presence of hemopoietic microenvironments. Marshall
Lichtman and coworkers deal with the structural analysis of
bone marrow and, particularly, the relevance of this structure
to the last stage of hemopoiesis, i.e., the egress of mature cells
into the circulation. Robert McCuskey, one of the few who
uses the exacting technique of in vivo microscopy, describes
the contribution of this unique method to our understanding
of the hemopoietic microenvironment. Fatty involution of
marrow and the role of adipose tissue, the strange bedfellow
of hemopoietic tissue, is the subject of another chapter. A
cellular ester membrane model has been useful in elucidating
many aspects of microenvironmental control of hemopoiesis.
This area will be reviewed by William Knospe.
Three chapters deal with the cellular components of the
stroma. In a comprehensive chapter, Mati Shaklai describes
cellular components of stroma in vivo at a morphologic level,
but also makes a correlative comparison with an in vitro sys
tem. Peter Quesenberry discusses the stroma in long-term
marrow culture. In the past few years, many of these stromal
cells have been cloned, and the study of their structural
functional characteristics are expected to answer certain
remaining questions. Dov Zipori will review this area. The
interface of immune and hemopoietic systems and the modu-
Preface vii
lation of hemopoiesis by monocytes and T-Iymphocytes are
treated in a chapter by Joao Ascensao and Esmail Zanjani,
who have also considered the immune nature of failure of
hemopoiesis. In analogy with "seed" and "soil," we may then
speak of the "worm" to identify one pathogenesis of marrow
failure.
The role of extracellular matrix is coming into focus, not
only in the regulation of hemopoiesis, but also as a regulatory
factor in cell biology in general. Renate Gay and colleagues
will provide and introduction to this area and will synthesize
our knowledge of noncollagenous matrix in the regulation of
hemopoiesis. The role of the collagenous matrix will be
treated in a different chapter by Kenneth Zuckerman and
coworkers. Finally, the development of knowledge generally
aims at applications, and thus, N. T. Shahidi will discuss the
potential clinical applications of this field.
Therefore, this volume is intended as a reading source
for all investigators in experimental hematology, but also
provides a reference source for hematologists, cell biologists,
experimental pathologists, immunologists, and even bio
chemists.
Among many, I am grateful to Kenneth Brinkhaus, who
appreciated the void of literature in this area and persuaded
me to undertake this task, a task that would have been impos
sible without the dedicated and highly organized adminis
trative assistance of Jackie Davis. I am also indebted to the
authors of the individual chapters, many of whom tolerated,
with good humor, my frequent and often repetitive vexing
requests for revisions. If this volume as a whole is more than
the sum of its parts, the credit belongs to them.
Mehdi Tavassoli
Preface
Vtlt
References
Tavassoli, M. (1980), Blood, Pure and Eloquent (Wintrobe, M. M., ed.),
McGraw Hill, New York, pp. 57-79.
Neumann, E. (1968), Zentralbl. Med. Wissensch. 6,689.
Danchakoff, V. (1916), Anat. Rec. 10,397-414.
Till, J. E. and McCulloch, E. A. (1961), Radiat. Res. 14, 213-222.
Trentin, J. J. (1970), Regulation of Hematopoiesis (Gordon, A. 5., ed.), Apple
ton-Century-Crofts, New York, pp. 161-186.
Dedication
To Marie, Ali, Javad, and Cherine
for their understanding and encouragements.
Contents
Preface ................................................................................. v
Contributors ............................................................................. xxi
Hemopoietic Microenvironments
Historical Perspectives, Status, and Projections
John J. Trentin
Introduction ................................................................................... 1
Definition ....................................................................................... 3
Radiation Protection by Marrow Transplantation ................. .4
The Spleen Colony Assay ............................................................ 5
Antecedents of the Hemopoietic Microenvironment
Concept ...................................................................................... 5
Homing .................................................................................. 5
Unexplained Failure of Marrow Isografts ........................ 7
Spleen Colony Types ................................................................... 9
Decision .................................................................................. 9
Spleen Colony Retransplantation ............................................ 14
Effect of Erythropoietin Deprivation on Spleen
Colony Types .......................................................................... 18
Visualization of Erythropoietin-Sensitive
Stem Cell Colonies .................................................................. 20
Decision for Lineage-Specific Differentiation ........................ 23
Endoc1onal Origin of the Second Line of Differentiation ..... 25
The Working Hypothesis .......................................................... 28
Tests of the Working Hypothesis ............................................. 29
Xl
