Getting more for your marrow: Boosting hematopoietic stem cell numbers with PGE2

Hagedorn, Elliott J.; Durand, Ellen M.; Fast, Eva M.; Zon, Leonard I.

doi:10.1016/j.yexcr.2014.07.030

Cited by 54 publications

(36 citation statements)

References 39 publications

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“…The ability of PGE2 to promote hematopoiesis has been documented by two types of experiments: (i) ex vivo treatment of hematopoietic stem cells with dmPGE2 improves stem cell engraftment and consequent survival of mice, and (ii) administration of PGE2 or dmPGE2 to sub-lethally irradiated mice accelerates hematopoietic recovery and increases numbers of the short-term subtype of hematopoietic stem cells (11, 13–17, 24–27). Previous work also revealed that dmPGE2-treated cells have increased levels of cyclic AMP, increased expression of CXCR4 and survivin, decreased apoptosis, and increased homing to the bone marrow stem cell niche (11, 14–16, 24, 25, 27).…”

Section: Resultsmentioning

confidence: 99%

Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration

Zhang

Desai

Yang

et al. 2015

Science

240

273

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Tissue regeneration is a medical challenge faced in injury from disease and during medical treatments such as bone marrow transplantation. Prostaglandin PGE2, which supports expansion of several types of tissue stem cells, is a candidate therapeutic target for promoting tissue regeneration in vivo. Here we show that inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a prostaglandin-degrading enzyme, potentiates tissue regeneration in multiple organs in mice. In a chemical screen, we identify a small-molecule inhibitor of 15-PGDH (SW033291) that increases prostaglandin PGE2 levels in bone marrow and other tissues. SW033291 accelerates hematopoietic recovery in mice receiving a bone marrow transplant. SW033291 also promotes tissue regeneration in mouse models of colon and liver injury. Tissues from 15-PGDH knockout mice demonstrate similar increased regenerative capacity. These findings raise the possibility that inhibiting 15-PGDH could be a useful therapeutic strategy in several distinct clinical settings.

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Section: Resultsmentioning

confidence: 99%

Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration

Zhang

Desai

Yang

et al. 2015

Science

240

273

View full text Add to dashboard Cite

show abstract

“…Another area of active development is to improve engraftment of transplanted HSPCs through the use of homing promoting effectors (reviewed in [117,118] inhibitor CHIR-911 [123], the histone deacetylase inhibitor valproic acid [124][125][126], the glycosaminoglycans hyaluronic acid [127], and complement molecule C3a [128,129] to name a few.…”

Section: Molecules That Promote Engraftment Through Improved Homingmentioning

confidence: 99%

Advances in umbilical cord blood stem cell expansion and clinical translation

Pineault

Abu‐Khader

2015

Experimental Hematology

108

101

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“…Ex vivo treatment of one of the two UCB units using prostaglandin E2 (dmPGE2) aimed at enhancing HSC homing by upregulating CXCR4 and HSC survival (FT1050; ProHema) [102][103][104][105][106].…”

Section: IIImentioning

confidence: 99%

“…In a subsequent similar clinical trial, but for which the dmPGE2 treatment of the UCB cells was irst optimized, improved time to neutrophil recovery (median 1 .5 days) was observed when compared with historical controls (21 days) and with the dmPGE2 primed UCB unit engrafting in over 80% of the patients. This has preceded to a Phase II clinical trial [106], and recent studies suggest that dmPGE2 may modulate Wnt signaling in UCB T cells and enhance immune reconstitution postransplant [103]. The efects of dmPGE2 in patients undergoing myeloablative conditioning are unknown.…”

Section: IVmentioning

confidence: 99%

Umbilical Cord Blood Hematopoietic Stem and Progenitor Cell Expansion for Therapeutic Use

Watt¹,

Hua²

2017

Umbilical Cord Blood Banking for Clinical Application and Regenerative Medicine

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Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for severe hematological malignancies and other severe disorders of the blood, immune system, and bone marrow. It is the most successful regenerative therapy to date, with 2013 marking the one millionth HSCT and the 25th anniversary of the irst umbilical cord blood (UCB) HSCT. UCB has most often been used for allogeneic HSCT when a matched bone marrow or peripheral blood donor is unavailable. Recently, novel genome editing technologies to correct inherited gene disorders or to modulate biomarkers/ receptors on HSC and the potential use of HSCT for a variety of other nonmalignant conditions have led to a surge of interest in autologous HSCT, with the HSC source depending on the condition to be treated. UCB HSCs may be used to generate red blood cells, granulocytes, or platelets ex vivo for transfusion into diicult-to-transfuse patients. Alternatively, UCB may be reprogrammed to induced pluripotent stem cells or used to generate cell lines, which can then be diferentiated into diferent cell lineages for transfusion or used as diagnostic reagents. Disadvantages of UCB are its restricted cell numbers and delayed hematological engraftment. Here, UCB HSC expansion/ manipulation ex vivo and clinical applications are addressed.

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Getting more for your marrow: Boosting hematopoietic stem cell numbers with PGE2

Cited by 54 publications

References 39 publications

Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration

Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration

Advances in umbilical cord blood stem cell expansion and clinical translation

Umbilical Cord Blood Hematopoietic Stem and Progenitor Cell Expansion for Therapeutic Use

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