Engraftment Efficiency after Intra-Bone Marrow versus Intravenous Transplantation of Bone Marrow Cells in a Canine Nonmyeloablative Dog Leukocyte Antigen-Identical Transplantation Model.
An intra-bone marrow (IBM) hematopoietic stem cell transplantation (HSCT) is assumed to optimize the homing process and therefore to improve engraftment as well as hematopoietic recovery compared with conventional i.v. HSCT. This study investigated the feasibility and efficacy of IBM HSCT after nonmyeloablative conditioning in an allogeneic canine HSCT model. Two study cohorts received IBM HSCT of either density gradient (IBM-I, n = 7) or buffy coat (IBM-II, n = 6) enriched bone marrow cells. An historical i.v. HSCT cohort served as control. Before allogeneic HSCT experiments were performed, we investigated the feasibility of IBM HSCT by using technetium-99m marked autologous grafts. Scintigraphic analyses confirmed that most IBM-injected autologous cells remained at the injection sites, independent of the applied volume. In addition, cell migration to other bones occurred. The enrichment process led to different allogeneic graft volumes (IBM-I, 2 × 5 mL; IBM-II, 2 × 25 mL) and significantly lower counts of total nucleated cells in IBM-I grafts compared with IBM-II grafts (1.6 × 108/kg versus 3.8 × 108/kg). After allogeneic HSCT, dogs of the IBM-I group showed a delayed engraftment with lower levels of donor chimerism when compared with IBM-II or to i.v. HSCT. Dogs of the IBM-II group tended to reveal slightly faster early leukocyte engraftment kinetics than intravenously transplanted animals. However, thrombocytopenia was significantly prolonged in both IBM groups when compared with i.v. HSCT. In conclusion, IBM HSCT is feasible in a nonmyeloablative HSCT setting but failed to significantly improve engraftment kinetics and hematopoietic recovery in comparison with conventional i.v. HSCT.
Department of Medicine III-Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.
Sandra
S
Lange
Department of Medicine III-Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.
Anne
A
Steder
Department of Medicine III-Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.
Doreen
D
Killian
Department of Medicine III-Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.
Gudrun
G
Knuebel
Department of Medicine III-Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.
Anett
A
Sekora
Department of Radiotherapy, University of Rostock, Rostock, Germany.
Heike
H
Vogel
Institute of Legal Medicine, University of Rostock, Rostock, Germany.
Iris
I
Lindner
Clinic for Nuclear Medicine, University of Rostock, Rostock, Germany.
Simone
S
Dunkelmann
Institute of Pathology, University of Rostock, Rostock, Germany.
Friedrich
F
Prall
Department of Medicine III-Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.
Hugo
H
Murua Escobar
Department of Medicine III-Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.
Mathias
M
Freund
Department of Medicine III-Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany. Electronic address: christian.junghanss@med.uni-rostock.de.
Christian
C
Junghanss
D064591:Allografts; D000818:Animals; D064592:Autografts; D016026:Bone Marrow Transplantation / Q000379:methods*; D002465:Cell Movement; D004285:Dogs; D006085:Graft Survival; D006648:Histocompatibility; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D017148:Infusions, Intraosseous; D007262:Infusions, Intravenous; D008297:Male; D019172:Transplantation Conditioning
D015395:Histocompatibility Antigens Class I; C039692:histocompatibility antigen DLA
Allogeneic; Cell migration; Dog; Intra–bone marrow hematopoietic stem cell transplantation; Nonmyeloablative conditioning