Optimization of intrabone delivery of hematopoietic progenitor cells in a swine model using cell radiolabeling with [89]zirconium

Jeremy Mark Pantin, R. F. Hoyt, O. Aras, N. Sato, M. Y. Chen, T. Hunt, R. Clevenger, P. Eclarinal, S. Adler, P. Choyke, Richard W. Childs

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Intrabone (IB) hematopoietic cell transplantation (HCT) of umbilical cord blood in humans remains experimental and the technique has not been optimized. It is unknown whether hematopoietic progenitor cells (HPCs) injected IB are initially retained in the marrow or rapidly enter into the venous circulation before homing to the marrow. To develop an IB-injection technique that maximizes HPC marrow-retention, we tracked radiolabeled human HPCs following IB-injection into swine. We developed a method to radionuclide-label HPCs using a long-lived positron emitter 89Zr and protamine sulfate that resulted in cellular-retention of low-dose radioactivity. This approach achieved radioactivity levels sufficient for detection by positron emission tomography with both high sensitivity and spatial resolution when fused with computed tomography. We found that conditions utilized in pilot IB-HCT clinical trials conducted by others led to both rapid drainage into the central venous circulation and cellular extravasation into surrounding muscle and soft tissues. By optimizing the needle design, using continuous real-time intra-marrow pressure monitoring, and by reducing the infusion-volume and infusion-rate, we overcame this limitation and achieved high retention of HPCs in the marrow. This method of IB cellular delivery is readily applicable in the clinic and could be utilized in future investigational IB-HCT trials aimed at maximizing marrow retention of HPCs.

Original languageEnglish (US)
Pages (from-to)606-617
Number of pages12
JournalAmerican Journal of Transplantation
Volume15
Issue number3
DOIs
StatePublished - Mar 1 2015

Keywords

  • animal models: porcine
  • basic (laboratory) research/science
  • bone marrow
  • clinical research/practice
  • diagnostic techniques and imaging: positron emission tomography
  • graft survival
  • graft-versus-host disease (GVHD)
  • hematology/oncology
  • hematopoietic stem cell transplantation
  • monitoring: physiologic
  • xenotransplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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    Pantin, J. M., Hoyt, R. F., Aras, O., Sato, N., Chen, M. Y., Hunt, T., Clevenger, R., Eclarinal, P., Adler, S., Choyke, P., & Childs, R. W. (2015). Optimization of intrabone delivery of hematopoietic progenitor cells in a swine model using cell radiolabeling with [89]zirconium. American Journal of Transplantation, 15(3), 606-617. https://doi.org/10.1111/ajt.13007