Erythropoietin modulation is associated with improved homing and engraftment after umbilical cord blood transplantation

Omar S. Aljitawi, Soumen Paul, Avishek Ganguly, Tara L. Lin, Sid Ganguly, George Vielhauer, Maegan L. Capitano, Amy Cantilena, Brea Lipe, Jonathan D. Mahnken, Amanda Wise, Abigale Berry, Anurag K. Singh, Leyla Shune, Christopher Lominska, Sunil Abhyankar, Dennis Allin, Mary Laughlin, Joseph P. McGuirk, Hal Broxmeyer

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Umbilical cord blood (UCB) engraftment is in part limited by graft cell dose, generally one log less than that of bone marrow (BM)/peripheral blood (PB) cell grafts. Strategies toward increasing hematopoietic stem/progenitor cell (HSPC) homing to BM have been assessed to improve UCB engraftment. Despite recent progress, a complete understanding of how HSPC homing and engraftment are regulated is still elusive. We provide evidence that blocking erythropoietin (EPO)-EPO receptor (R) signaling promotes homing to BM and early engraftment of UCB CD34+ cells. A significant population of UCB CD34+ HSPC expresses cell surface EPOR. Exposure of UCB CD34+ HSPC to EPO inhibits their migration and enhances erythroid differentiation. This migratory inhibitory effect was reversed by depleting EPOR expression on HSPC. Moreover, systemic reduction in EPO levels by hyperbaric oxygen (HBO) used in a preclinical mouse model and in a pilot clinical trial promoted homing of transplanted UCB CD34+ HSPC to BM. Such a systemic reduction of EPO in the host enhanced myeloid differentiation and improved BM homing of UCB CD34+ cells, an effect that was overcome with exogenous EPO administration. Of clinical relevance, HBO therapy before human UCB transplantation was well-tolerated and resulted in transient reduction in EPO with encouraging engraftment rates and kinetics. Our studies indicate that systemic reduction of EPO levels in the host or blocking EPO-EPOR signaling may be an effective strategy to improve BM homing and engraftment after allogeneic UCB transplantation. This clinical trial was registered at www.ClinicalTrials.gov (#NCT02099266).

Original languageEnglish (US)
Pages (from-to)3000-3010
Number of pages11
JournalBlood
Volume128
Issue number25
DOIs
StatePublished - Dec 22 2016

Fingerprint

Erythropoietin
Hematopoietic Stem Cells
Fetal Blood
Blood
Transplantation
Modulation
Stem cells
Bone
Bone Marrow
Blood Cells
Grafts
Oxygen
Erythropoietin Receptors
Clinical Trials
Transplants
Hyperbaric Oxygenation
Cells
Kinetics

ASJC Scopus subject areas

  • Immunology
  • Biochemistry
  • Hematology
  • Cell Biology

Cite this

Erythropoietin modulation is associated with improved homing and engraftment after umbilical cord blood transplantation. / Aljitawi, Omar S.; Paul, Soumen; Ganguly, Avishek; Lin, Tara L.; Ganguly, Sid; Vielhauer, George; Capitano, Maegan L.; Cantilena, Amy; Lipe, Brea; Mahnken, Jonathan D.; Wise, Amanda; Berry, Abigale; Singh, Anurag K.; Shune, Leyla; Lominska, Christopher; Abhyankar, Sunil; Allin, Dennis; Laughlin, Mary; McGuirk, Joseph P.; Broxmeyer, Hal.

In: Blood, Vol. 128, No. 25, 22.12.2016, p. 3000-3010.

Research output: Contribution to journalArticle

Aljitawi, OS, Paul, S, Ganguly, A, Lin, TL, Ganguly, S, Vielhauer, G, Capitano, ML, Cantilena, A, Lipe, B, Mahnken, JD, Wise, A, Berry, A, Singh, AK, Shune, L, Lominska, C, Abhyankar, S, Allin, D, Laughlin, M, McGuirk, JP & Broxmeyer, H 2016, 'Erythropoietin modulation is associated with improved homing and engraftment after umbilical cord blood transplantation', Blood, vol. 128, no. 25, pp. 3000-3010. https://doi.org/10.1182/blood-2016-05-715292
Aljitawi, Omar S. ; Paul, Soumen ; Ganguly, Avishek ; Lin, Tara L. ; Ganguly, Sid ; Vielhauer, George ; Capitano, Maegan L. ; Cantilena, Amy ; Lipe, Brea ; Mahnken, Jonathan D. ; Wise, Amanda ; Berry, Abigale ; Singh, Anurag K. ; Shune, Leyla ; Lominska, Christopher ; Abhyankar, Sunil ; Allin, Dennis ; Laughlin, Mary ; McGuirk, Joseph P. ; Broxmeyer, Hal. / Erythropoietin modulation is associated with improved homing and engraftment after umbilical cord blood transplantation. In: Blood. 2016 ; Vol. 128, No. 25. pp. 3000-3010.
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abstract = "Umbilical cord blood (UCB) engraftment is in part limited by graft cell dose, generally one log less than that of bone marrow (BM)/peripheral blood (PB) cell grafts. Strategies toward increasing hematopoietic stem/progenitor cell (HSPC) homing to BM have been assessed to improve UCB engraftment. Despite recent progress, a complete understanding of how HSPC homing and engraftment are regulated is still elusive. We provide evidence that blocking erythropoietin (EPO)-EPO receptor (R) signaling promotes homing to BM and early engraftment of UCB CD34+ cells. A significant population of UCB CD34+ HSPC expresses cell surface EPOR. Exposure of UCB CD34+ HSPC to EPO inhibits their migration and enhances erythroid differentiation. This migratory inhibitory effect was reversed by depleting EPOR expression on HSPC. Moreover, systemic reduction in EPO levels by hyperbaric oxygen (HBO) used in a preclinical mouse model and in a pilot clinical trial promoted homing of transplanted UCB CD34+ HSPC to BM. Such a systemic reduction of EPO in the host enhanced myeloid differentiation and improved BM homing of UCB CD34+ cells, an effect that was overcome with exogenous EPO administration. Of clinical relevance, HBO therapy before human UCB transplantation was well-tolerated and resulted in transient reduction in EPO with encouraging engraftment rates and kinetics. Our studies indicate that systemic reduction of EPO levels in the host or blocking EPO-EPOR signaling may be an effective strategy to improve BM homing and engraftment after allogeneic UCB transplantation. This clinical trial was registered at www.ClinicalTrials.gov (#NCT02099266).",
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AU - Aljitawi, Omar S.

AU - Paul, Soumen

AU - Ganguly, Avishek

AU - Lin, Tara L.

AU - Ganguly, Sid

AU - Vielhauer, George

AU - Capitano, Maegan L.

AU - Cantilena, Amy

AU - Lipe, Brea

AU - Mahnken, Jonathan D.

AU - Wise, Amanda

AU - Berry, Abigale

AU - Singh, Anurag K.

AU - Shune, Leyla

AU - Lominska, Christopher

AU - Abhyankar, Sunil

AU - Allin, Dennis

AU - Laughlin, Mary

AU - McGuirk, Joseph P.

AU - Broxmeyer, Hal

PY - 2016/12/22

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N2 - Umbilical cord blood (UCB) engraftment is in part limited by graft cell dose, generally one log less than that of bone marrow (BM)/peripheral blood (PB) cell grafts. Strategies toward increasing hematopoietic stem/progenitor cell (HSPC) homing to BM have been assessed to improve UCB engraftment. Despite recent progress, a complete understanding of how HSPC homing and engraftment are regulated is still elusive. We provide evidence that blocking erythropoietin (EPO)-EPO receptor (R) signaling promotes homing to BM and early engraftment of UCB CD34+ cells. A significant population of UCB CD34+ HSPC expresses cell surface EPOR. Exposure of UCB CD34+ HSPC to EPO inhibits their migration and enhances erythroid differentiation. This migratory inhibitory effect was reversed by depleting EPOR expression on HSPC. Moreover, systemic reduction in EPO levels by hyperbaric oxygen (HBO) used in a preclinical mouse model and in a pilot clinical trial promoted homing of transplanted UCB CD34+ HSPC to BM. Such a systemic reduction of EPO in the host enhanced myeloid differentiation and improved BM homing of UCB CD34+ cells, an effect that was overcome with exogenous EPO administration. Of clinical relevance, HBO therapy before human UCB transplantation was well-tolerated and resulted in transient reduction in EPO with encouraging engraftment rates and kinetics. Our studies indicate that systemic reduction of EPO levels in the host or blocking EPO-EPOR signaling may be an effective strategy to improve BM homing and engraftment after allogeneic UCB transplantation. This clinical trial was registered at www.ClinicalTrials.gov (#NCT02099266).

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