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Optimization of Intrabone Delivery of Hematopoietic Progenitor Cells in a Swine Model Using Cell Radiolabeling with [89]zirconium
Author(s) -
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.
Publication year - 2015
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.13007
Subject(s) - medicine , progenitor cell , haematopoiesis , transplantation , umbilical cord , homing (biology) , bone marrow , nuclear medicine , cd34 , stem cell , cancer research , pathology , immunology , surgery , biology , microbiology and biotechnology , ecology
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 89 Zr 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.