Intrabone transplantation of CD34+ cells with optimized delivery does not enhance engraftment in a rhesus macaque model
| Autor: | Cynthia E. Dunbar, Theresa Engels, Aylin C. Bonifacino, John F. Tisdale, Robert E. Donahue, Robert F. Hoyt, Randall R. Clevenger, Jan K Davidson-Moncada, Naoya Uchida, Kate Stringaris, William G. Telford, Mark E. Metzger, Richard W. Childs, Timothy Hunt, Noriko Sato, Allen E. Krouse, Peter L. Choyke, Robert Reger, Lydia N. Raines, Jeremy Pantin |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Yellow fluorescent protein Population CD34 Antigens CD34 Umbilical cord Flow cytometry 03 medical and health sciences 0302 clinical medicine medicine Animals Progenitor cell education Radioisotopes Transplantation education.field_of_study medicine.diagnostic_test biology Chemistry Hematopoietic Stem Cell Transplantation Hematology Hematopoietic Stem Cells Macaca mulatta Haematopoiesis 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research biology.protein Zirconium |
| Zdroj: | Blood Adv |
| ISSN: | 2473-9537 2473-9529 |
| DOI: | 10.1182/bloodadvances.2020003040 |
| Popis: | Intrabone (IB) injection of umbilical cord blood has been proposed as a potential mechanism to improve transplant engraftment and prevent graft failure. However, conventional IB techniques produce low retention of transplanted cells in the marrow. To overcome this barrier, we developed an optimized IB (OIB) injection method using low-volume, computer-controlled slow infusion that promotes cellular retention in the marrow. Here, we compare engraftment of CD34+ cells transplanted in a myeloablative rhesus macaque (RM) model using the OIB method compared with IV delivery. RM CD34+ cells obtained by apheresis were split equally for transduction with lentiviral vectors encoding either green fluorescent protein or yellow fluorescent protein reporters. Following conditioning, one marked autologous population of CD34+ cells was injected directly IB using the OIB method and the other was injected via slow IV push into the same animal (n = 3). Daily flow cytometry of blood quantified the proportion of engrafting cells deriving from each source. Marrow retention was examined using positron emission tomography/computed tomography imaging of 89Zirconium (89Zr)-oxine–labeled CD34+ cells. CD34+ cells injected via the OIB method were retained in the marrow and engrafted in all 3 animals. However, OIB-transplanted progenitor cells did not engraft any faster than those delivered IV and contributed significantly less to hematopoiesis than IV-delivered cells at all time points. Rigorous testing of our OIB delivery system in a competitive RM myeloablative transplant model showed no engraftment advantage over conventional IV infusion. Given the increased complexity and potential risks of IB vs IV approaches, our data do not support IB transplantation as a strategy to improve hematopoietic engraftment. |
| Databáze: | OpenAIRE |
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