Prostaglandin E2 Enhances Human Cord Blood Stem Cell Xenotransplants and Shows Long-Term Safety in Preclinical Nonhuman Primate Transplant Models

被引：214

作者：

Goessling, Wolfram ^{[1
,2
,3
,4
]}

Allen, Robyn S. ^{[5
]}

Guan, Xiao ^{[6
]}

Jin, Ping ^{[7
]}

Uchida, Naoya ^{[8
]}

Dovey, Michael ^{[9
]}

Harris, James M. ^{[9
]}

Metzger, Mark E. ^{[5
]}

Bonifacino, Aylin C. ^{[5
]}

Stroncek, David ^{[7
]}

Stegner, Joseph ^{[10
]}

Armant, Myriam ^{[10
]}

Schlaeger, Thorsten ^{[6
]}

Tisdale, John F. ^{[8
]}

Zon, Leonard I. ^{[1
,2
,6
,11
]}

Donahue, Robert E. ^{[5
]}

North, Trista E. ^{[1
,2
,9
]}

机构：

[1] Harvard Stem Cell Inst, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Boston, MA 02115 USA

[3] Brigham & Womens Hosp, Dana Farber Canc Inst, Gastrointestinal Canc Ctr, Div Genet, Boston, MA 02115 USA

[4] Brigham & Womens Hosp, Dana Farber Canc Inst, Gastrointestinal Canc Ctr, Div Gastroenterol, Boston, MA 02115 USA

[5] NHLBI, Hematol Branch, NIH, Rockville, MD 20850 USA

[6] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA

[7] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA

[8] NIDDK, Mol & Clin Hematol Branch, NHLBI, NIH, Bethesda, MD 20892 USA

[9] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA

[10] Immune Dis Inst, Ctr Human Cell Therapy, Boston, MA 02115 USA

[11] Howard Hughes Med Inst, Boston, MA 02115 USA

来源：

CELL STEM CELL | 2011年 / 8卷 / 04期

基金：

美国国家卫生研究院;

关键词：

BONE-MARROW; PROGENITOR CELLS; EXPANSION; MOBILIZATION; REPOPULATION; ENGRAFTMENT; RECEPTOR; DONORS;

D O I：

10.1016/j.stem.2011.02.003

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Hematopoietic stem cells (HSCs) are used in transplantation therapy to reconstitute the hematopoietic system. Human cord blood (hCB) transplantation has emerged as an attractive alternative treatment option when traditional HSC sources are unavailable; however, the absolute number of hCB HSCE.; transplanted is significantly lower than bone marrow or mobilized peripheral blood stem cells (MPBSCs). We previously demonstrated that dimethyl-prostaglandin E2 (dmPGE2), increased HSCs in vertebrate models. Here, we describe preclinical analyses of the therapeutic potential of dmPGE2 treatment by using human and nonhuman primate HSCs. dmPGE2 significantly increased total human hematopoietic colony formation in vitro and enhanced engraftment of unfractionated and CD34(+) hCB after xenotransplantation. In nonhuman primate autologous transplantation, dmPGE2-treated CD34(+) MPBSCs showed stable multilineage engraftment over 1 year postinfusion. Together, our analyses indicated that dmPGE2 mediates conserved responses in HSCs from human and nonhuman primates and provided sufficient preclinical information to support proceeding to an FDA-approved phase 1 clinical trial.

引用

页码：445 / 458

页数：14

共 32 条

[31] Development of a Human Immunodeficiency Virus Type 1-Based Lentiviral Vector That Allows Efficient Transduction of both Human and Rhesus Blood Cells [J].