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Improved hematopoiesis in anemic Sl/Sld mice by splenectomy and therapeutic
transplantation of a hematopoietic microenvironment
P Anklesaria, TJ FitzGerald, K Kase, A Ohara and JS Greenberger
Department of Radiation Oncology, University of Massachusetts Medical
Center, Worcester 01655.
The ability of a clonal hematopoiesis-supportive bone-marrow stromal cell
line GBlneor to engraft and alter the microenvironment-induced anemia of
Sl/Sld mice was studied. Prior to stromal cell transplantation, Sl/Sld mice
received 1 Gy total body irradiation (TBI) and 13 Gy to the right hind
limb. Two months after intravenous (IV) injection of 5 x 10(5) GBlneor
cells, 54.4% +/- 17.0% donor origin (G418r) colony-forming cells were
recovered from the right hind limb of Sl/Sld mice. Long-term bone marrow
cultures (LTBMCs) established from GBlneor-transplanted mice produced 189.5
CFU-GEMM-forming progenitors/flask over 10 weeks compared with 52.7 +/- 6.2
CFU-GEMM forming progenitors/flask from irradiated nontransplanted Sl/Sld
mice. A partial correction of macrocytic anemia was detected 2 months after
GBlneor transplantation in splenectomized, irradiated Sl/Sld mice (HgB 7.2
+/- 0.4 g/dL; MCV 68.3 +/- 7.0 fL) compared to splenectomized, irradiated,
nontransplanted Sl/Sld mice (HgB 5.5 +/- 1.1 g/dL; MCV 76 +/- 8.5 fL) or
control Sl/Sld mice (HgB 5.4 +/- 0.5 g/dL; MCV 82.4 +/- 1.3 fL). Mean RBC
volume distribution analysis showed a 2.5-fold increase in percentage of
peripheral blood RBCs with MCV less than or equal to 45 fL and confirmed
reduction of the MCV in splenectomized- GBlneor-transplanted mice compared
to control Sl/Sld mice. A hematopoiesis-suppressive clonal stromal cell
line derived from LTBMCs of Sl/Sld mice (Sldneor) engrafted as effectively
(43.5% +/- 1.2% G418r CFU-F/limb) as did GBlneor cells (38.3% +/- 0.16%
G418r CFU-F/limb) to the irradiated right hind limbs of C57Bl/6 mice.
LTBMCs established after 2 or 6 months from Sldneor-transplanted mice
showed decreased hematopoiesis (182 +/- 12 [2 months] and 3494.3 +/- 408.1
[6 months] CFU-GEMM forming progenitors/flask over 10 weeks) compared to
those established from GBlneor-transplanted mice (5980 +/- 530 [2 months]
and 7728 +/- 607, [6 months] CFU-GEMM progenitors forming/flask). Thus,
transplantation of clonal bone-marrow stromal cell lines in vivo can stably
transfer their physiologic properties to normal or mutant mice.
Volume 74,
Issue 3,
pp. 1144-1151,
08/15/1989
Copyright © 1989 by The American Society of Hematology
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