TY - JOUR
T1 - Influence of hemoglobin vesicles, cellular-type artificial oxygen carriers, on human umbilical cord blood hematopoietic progenitor cells in vitro
AU - Yamaguchi, Miki
AU - Fujihara, Mitsuhiro
AU - Wakamoto, Shinobu
AU - Sakai, Hiromi
AU - Takeoka, Shinji
AU - Tsuchida, Eishun
AU - Azuma, Hiroshi
AU - Ikeda, Hisami
PY - 2009/1/1
Y1 - 2009/1/1
N2 - Hemoglobin vesicles (HbVs), liposomal oxygen carriers containing human hemoglobin, are candidates for development as clinically useful blood substitutes. Although HbVs are shown to distribute transiently into the bone marrow in animal models, the influence of HbVs on human hematopoietic stem/progenitor cells has not yet been studied. Therefore, we investigated the influence of HbVs at a concentration of up to 3 vol/vol % on the clonogenic activity (in semisolid culture) and proliferative activity (in liquid culture) of human hematopoietic progenitor cells derived from umbilical cord blood (CB) in vitro. Continuous exposure of CB mononuclear cells to HbVs tended to decrease the number and size of mature-committed colonies and most notably reduced the number of colonies of high-proliferative potential colony-forming cells (HPP-CFC). In contrast, exposure to HbVs for 20 h or 3 days, which is more relevant to the clinical setting, had no effect on the number of mature-committed colonies and only modestly decreased the number of HPP-CFC. Continuous exposure (10 days) to HbVs significantly suppressed the cellular proliferation and differentiation of both the erythroid and myeloid lineages in liquid culture. Again, short exposure (20 h or 3 days) did not affect these parameters. Thus, our results show that HbVs, under conditions relevant to the clinical setting, have no adverse effect on human CB hematopoietic progenitor activity in vitro.
AB - Hemoglobin vesicles (HbVs), liposomal oxygen carriers containing human hemoglobin, are candidates for development as clinically useful blood substitutes. Although HbVs are shown to distribute transiently into the bone marrow in animal models, the influence of HbVs on human hematopoietic stem/progenitor cells has not yet been studied. Therefore, we investigated the influence of HbVs at a concentration of up to 3 vol/vol % on the clonogenic activity (in semisolid culture) and proliferative activity (in liquid culture) of human hematopoietic progenitor cells derived from umbilical cord blood (CB) in vitro. Continuous exposure of CB mononuclear cells to HbVs tended to decrease the number and size of mature-committed colonies and most notably reduced the number of colonies of high-proliferative potential colony-forming cells (HPP-CFC). In contrast, exposure to HbVs for 20 h or 3 days, which is more relevant to the clinical setting, had no effect on the number of mature-committed colonies and only modestly decreased the number of HPP-CFC. Continuous exposure (10 days) to HbVs significantly suppressed the cellular proliferation and differentiation of both the erythroid and myeloid lineages in liquid culture. Again, short exposure (20 h or 3 days) did not affect these parameters. Thus, our results show that HbVs, under conditions relevant to the clinical setting, have no adverse effect on human CB hematopoietic progenitor activity in vitro.
KW - Biocompatibility
KW - Colony assay
KW - Hematopoietic progenitor cells
KW - Hemoglobin-vesicles
KW - Liposome-encapsulated hemoglobin
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U2 - 10.1002/jbm.a.31857
DO - 10.1002/jbm.a.31857
M3 - Article
C2 - 18257068
AN - SCOPUS:57449097000
VL - 88
SP - 34
EP - 42
JO - Journal of Biomedical Materials Research - Part A
JF - Journal of Biomedical Materials Research - Part A
SN - 1549-3296
IS - 1
ER -