Thrombospondins deployed by thrombopoietic cells determine angiogenic switch and extent of revascularization
J. Clin. Invest. Hans-Georg Kopp, et al. 116:3277 doi:10.1172/JCI29314 [
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Figure 4TSP-deficient thrombocytotic phenotype is transplantable.
(
A–
C) Lethally irradiated (9.5 Gy) WT control mice were transplanted with
TSP-DKO bone marrow and
TSP-DKO mice were transplanted with WT bone marrow. Ninety days after transplantation, platelet counts were 1.7 ± 0.1 × 10
6/μl in WT recipients transplanted with
TSP-DKO bone marrow and 1.4 ± 0.6 10
6/μl in
TSP-DKO recipients transplanted with WT bone marrow.
P < 0.04. Platelet (
A) and megakaryocyte levels (
B) and vascular density (
C) were determined in the transplanted mice. (
D) When 5-FU was given (250 mg/kg i.v.) to the same mice, WT mice with
TSP-deficient hematopoiesis displayed a faster platelet recovery than
TSP-deficient mice that had been transplanted with WT bone marrow. On day 10, platelet levels were 0.18 ± 0.05 × 10
6/μl in
TSP-DKO mice with WT hematopoiesis compared with 1.6 ± 0.27 × 10
6/μl in the WT recipients of
TSP-deficient bone marrow (
P < 0.03). Therefore, TSP from transplanted megakaryocytes, rather than TSP presented or secreted by nontransplanted bone marrow stromal components, may regulate megakaryopoiesis and thrombopoiesis following myelosuppression. *
P < 0.05.