Engraftment Efficiency after Intra–Bone Marrow versus Intravenous Transplantation of Bone Marrow Cells in a Canine Nonmyeloablative Dog Leukocyte Antigen-Identical Transplantation Model

Abstract

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 × 10/kg versus 3.8 × 10/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.

Intra-bone marrow co-transplantation of umbilical cord mesenchymal stem cells promotes the engraftment of umbilical cord blood stem cells in iron overload NOD/SCID mice

“…The results suggested that IBM injection might be able to reduce the loss of HSC in the reticuloendothelial system and promote the homing of HSC. This finding was inconsistent with previous reports showing IBM is an effective approach for HSCT compared to traditional IV transplantation [10,12,13]. However, we found there was no difference between IBM and IV groups regarding the engraftment rate of UCB-MNC when using the iron overload model.…”

Bone marrow stem cell applied in the canine veterinary clinics

“…Studies performed in the last years on hematopoietic stem cells from canine bone marrow. (Osgood et al 1939, Thomas et al 1962, Epstein et al 1967, Escobar et al 2012, Killian et al 2013, Sato et al 2013, Mathes et al 2014, Vrecenak et al 2014, Rosinski et al 2015, Suter et al 2015, Luangphakdy et al 2016, Lange et al 2017 Fig.2. Studies performed in the last years on mesenchymal stem cells from canine bone marrow.…”

Noninvasive Tracking of Hematopoietic Stem Cells in a Bone Marrow Transplant Model

“…Of the 1694 articles identified in Scopus, after screening, 771 articles were excluded (416 reviews, 106 publications before 2000, 50 publications in other languages, and 199 duplicated in Pubmed search), and after assessing eligibility, 910 articles were excluded (287 reported no data about HSC and 623 reported no data about noninvasive imaging); thus, only 13 articles were included from this database. In total, only 21 nonduplicate full text articles were included in this review [9,11,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34], as depicted in Figure 1.…”

“…To study the dynamics of hematopoietic reconstitution, in which cells localize deep inside hematopoietic organs and other tissues, different modalities of molecular imaging are used for HSC tracking and engraftment, such as (i) optical imaging represented by bioluminescence imaging (BLI) [9,11,[16][17][18][19][20] and fluorescence imaging (FLI) [21][22][23][24][25], (ii) nuclear imaging represented by positron emission tomography (PET) [26][27][28] and single-photon emission computed tomography (SPECT) [29][30][31], and (iii) magnetic resonance imaging (MRI) [32][33][34].…”