Phase I/II Trial of StemRegenin-1 Expanded Umbilical Cord Blood Hematopoietic Stem Cells Supports Testing as a Stand-Alone Graft

John E. Wagner; Claudio G. Brunstein; Anthony E. Boitano; Todd E. Defor; David McKenna; Darin Sumstad; Bruce R. Blazar; Jakub Tolar; Chap Le; Julie Jones; Michael P. Cooke; Conrad C. Bleul

doi:10.1016/j.stem.2015.10.004

Phase I/II Trial of StemRegenin-1 Expanded Umbilical Cord Blood Hematopoietic Stem Cells Supports Testing as a Stand-Alone Graft

John E. Wagner, Claudio G. Brunstein, Anthony E. Boitano, Todd E. Defor, David McKenna, Darin Sumstad, Bruce R. Blazar, Jakub Tolar, Chap Le, Julie Jones, Michael P. Cooke, Conrad C. Bleul

Research output: Contribution to journal › Article › peer-review

259 Scopus citations

Abstract

Clinical application of umbilical cord blood (UCB) as a source of hematopoietic stem cells for transplantation is limited by low CD34+ cell dose, increased risk of graft failure, and slow hematopoietic recovery. While the cell dose limitation is partially mitigated by using two UCB units, larger-dosed single units would be preferable. We have evaluated the feasibility and safety of StemRegenin-1 (SR-1), an aryl hydrocarbon receptor antagonist that expands CD34+ cells, by placing one of the two units in expansion culture. SR-1 produced a 330-fold increase in CD34+ cells and led to engraftment in 17/17 patients at a median of 15 days for neutrophils and 49 days for platelets, significantly faster than in patients treated with unmanipulated UCB. Taken together, the marked expansion, absence of graft failure, and enhanced hematopoietic recovery support testing of SR-1 expansion as a stand-alone graft and suggest it may ameliorate a limitation of UCB transplant.

Original language	English (US)
Pages (from-to)	144-155
Number of pages	12
Journal	Cell Stem Cell
Volume	18
Issue number	1
DOIs	https://doi.org/10.1016/j.stem.2015.10.004
State	Published - Jan 7 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Inc.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access

10.1016/j.stem.2015.10.004

OpenUrl availability

Full text

Cite this

Wagner, J. E., Brunstein, C. G., Boitano, A. E., Defor, T. E., McKenna, D., Sumstad, D., Blazar, B. R., Tolar, J., Le, C., Jones, J., Cooke, M. P., & Bleul, C. C. (2016). Phase I/II Trial of StemRegenin-1 Expanded Umbilical Cord Blood Hematopoietic Stem Cells Supports Testing as a Stand-Alone Graft. Cell Stem Cell, 18(1), 144-155. https://doi.org/10.1016/j.stem.2015.10.004

@article{8598b7e7fdef4a80aedc1557c81f554f,

title = "Phase I/II Trial of StemRegenin-1 Expanded Umbilical Cord Blood Hematopoietic Stem Cells Supports Testing as a Stand-Alone Graft",

abstract = "Clinical application of umbilical cord blood (UCB) as a source of hematopoietic stem cells for transplantation is limited by low CD34+ cell dose, increased risk of graft failure, and slow hematopoietic recovery. While the cell dose limitation is partially mitigated by using two UCB units, larger-dosed single units would be preferable. We have evaluated the feasibility and safety of StemRegenin-1 (SR-1), an aryl hydrocarbon receptor antagonist that expands CD34+ cells, by placing one of the two units in expansion culture. SR-1 produced a 330-fold increase in CD34+ cells and led to engraftment in 17/17 patients at a median of 15 days for neutrophils and 49 days for platelets, significantly faster than in patients treated with unmanipulated UCB. Taken together, the marked expansion, absence of graft failure, and enhanced hematopoietic recovery support testing of SR-1 expansion as a stand-alone graft and suggest it may ameliorate a limitation of UCB transplant.",

author = "Wagner, {John E.} and Brunstein, {Claudio G.} and Boitano, {Anthony E.} and Defor, {Todd E.} and David McKenna and Darin Sumstad and Blazar, {Bruce R.} and Jakub Tolar and Chap Le and Julie Jones and Cooke, {Michael P.} and Bleul, {Conrad C.}",

note = "Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = jan,

day = "7",

doi = "10.1016/j.stem.2015.10.004",

language = "English (US)",

volume = "18",

pages = "144--155",

journal = "Cell Stem Cell",

issn = "1934-5909",

publisher = "Cell Press",

number = "1",

}

TY - JOUR

T1 - Phase I/II Trial of StemRegenin-1 Expanded Umbilical Cord Blood Hematopoietic Stem Cells Supports Testing as a Stand-Alone Graft

AU - Wagner, John E.

AU - Brunstein, Claudio G.

AU - Boitano, Anthony E.

AU - Defor, Todd E.

AU - McKenna, David

AU - Sumstad, Darin

AU - Blazar, Bruce R.

AU - Tolar, Jakub

AU - Le, Chap

AU - Jones, Julie

AU - Cooke, Michael P.

AU - Bleul, Conrad C.

PY - 2016/1/7

Y1 - 2016/1/7

N2 - Clinical application of umbilical cord blood (UCB) as a source of hematopoietic stem cells for transplantation is limited by low CD34+ cell dose, increased risk of graft failure, and slow hematopoietic recovery. While the cell dose limitation is partially mitigated by using two UCB units, larger-dosed single units would be preferable. We have evaluated the feasibility and safety of StemRegenin-1 (SR-1), an aryl hydrocarbon receptor antagonist that expands CD34+ cells, by placing one of the two units in expansion culture. SR-1 produced a 330-fold increase in CD34+ cells and led to engraftment in 17/17 patients at a median of 15 days for neutrophils and 49 days for platelets, significantly faster than in patients treated with unmanipulated UCB. Taken together, the marked expansion, absence of graft failure, and enhanced hematopoietic recovery support testing of SR-1 expansion as a stand-alone graft and suggest it may ameliorate a limitation of UCB transplant.

AB - Clinical application of umbilical cord blood (UCB) as a source of hematopoietic stem cells for transplantation is limited by low CD34+ cell dose, increased risk of graft failure, and slow hematopoietic recovery. While the cell dose limitation is partially mitigated by using two UCB units, larger-dosed single units would be preferable. We have evaluated the feasibility and safety of StemRegenin-1 (SR-1), an aryl hydrocarbon receptor antagonist that expands CD34+ cells, by placing one of the two units in expansion culture. SR-1 produced a 330-fold increase in CD34+ cells and led to engraftment in 17/17 patients at a median of 15 days for neutrophils and 49 days for platelets, significantly faster than in patients treated with unmanipulated UCB. Taken together, the marked expansion, absence of graft failure, and enhanced hematopoietic recovery support testing of SR-1 expansion as a stand-alone graft and suggest it may ameliorate a limitation of UCB transplant.

UR - http://www.scopus.com/inward/record.url?scp=84954201991&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84954201991&partnerID=8YFLogxK

U2 - 10.1016/j.stem.2015.10.004

DO - 10.1016/j.stem.2015.10.004

M3 - Article

C2 - 26669897

AN - SCOPUS:84954201991

SN - 1934-5909

VL - 18

SP - 144

EP - 155

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 1

ER -

Phase I/II Trial of StemRegenin-1 Expanded Umbilical Cord Blood Hematopoietic Stem Cells Supports Testing as a Stand-Alone Graft

Abstract

Bibliographical note

UN SDGs

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this