Caspase Inhibitor ZVAD-fmk Facilitates Engraftment of Donor Hematopoietic Stem Cells in Intra-Bone Marrow-Bone Marrow Transplantation

被引：8

作者：

Imai, Yuichiro ^{[1
,2
]}

Adachi, Yasushi ^{[1
,3
,4
]}

Shi, Ming ^{[1
]}

Shima, Chieko ^{[1
]}

Yanai, Seiji ^{[1
]}

Okigaki, Mitsuhiko ^{[5
]}

Yamashima, Tetsumori ^{[6
]}

Kaneko, Kazunari ^{[2
]}

Ikehara, Susumu ^{[1
,3
,4
]}

机构：

[1] Kansai Med Univ, Dept Pathol 1, Moriguchi, Osaka 5708506, Japan

[2] Kansai Med Univ, Dept Pediat, Moriguchi, Osaka 5708506, Japan

[3] Kansai Med Univ, Transplantat Ctr, Moriguchi, Osaka 5708506, Japan

[4] Kansai Med Univ, Regenerat Res Ctr Intractable Dis, Moriguchi, Osaka 5708506, Japan

[5] Kyoto Prefectural Univ, Sch Med, Dept Cardiovasc Med, Kamigyo Ku, Kyoto 606, Japan

[6] Kanazawa Univ, Grad Sch Med Sci, Div Neurosci, Dept Restorat Neurosurg, Kanazawa, Ishikawa, Japan

来源：

STEM CELLS AND DEVELOPMENT | 2010年 / 19卷 / 04期

关键词：

VERSUS-HOST-DISEASE; AUTOIMMUNE-DISEASES; PERIPHERAL-BLOOD; INJECTION; APOPTOSIS; ACTIVATION; RECOVERY; SURVIVAL; IMPROVES; PATIENT;

D O I：

10.1089/scd.2009.0251

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

When bone marrow transplantation (BMT) is carried out, survival of the donor hematopoietic stem cells is crucial to maintain donor hematopoiesis in the recipients. We have shown that intra bone marrow-bone marrow transplantation (IBM-BMT) can induce the rapid recovery of donor hematopoiesis and allow a reduction in radiation doses as a pretreatment for BMT. If IBM-BMT methodology can be further improved, BMT could be carried out more safely and more easily. In this experiment, we attempted to suppress apoptosis of donor hematopoietic cells using a caspase inhibitor, ZVAD-fmk, upon IBM-BMT in mouse allogeneic IBM-BMT. IBM-BMT with ZVAD-fmk induced superior engraftment of donor hematopoietic cells and greater numbers of day-12 colony-forming units of spleen (CFU-S) than IBM-BMT without ZVAD-fmk upon allogeneic BMT (C57BL/6 into BALB/c mice). ZVAD-fmk slightly suppressed apoptosis of whole BMCs, whereas it significantly suppressed apoptosis of c-kit(+)/Sca-1(+)/lineage(-) cells (KSL cells) in vitro. These results suggest that ZVAD-fmk can suppress apoptosis of hematopoietic stem cells and/or immature progenitor cells of the donor bone marrow cells, thereby accelerating the donor hematopoiesis.

引用

页码：461 / 467

页数：7

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