title: No Synergistic Effect of Cotransplantation of MSC and Ex Vivo TPO-Expanded CD34(+) Cord Blood Cells on Platelet Recovery and Bone Marrow Engraftment in NOD SCID Mice.
abstract: After cord blood (CB) transplantation, early platelet recovery in immune-deficient mice is obtained by expansion of CB CD34(+) cells with thrombopoietin (TPO) as single growth factor. Moreover, improvement of hematopoietic engraftment has been shown by cotransplantation of mesenchymal stem cells (MSC). We investigated whether a combination of both approaches would further enhance the outcome of CB transplantation in NOD SCID mice. NOD SCID mice were transplanted with either CB CD34(+) cells, CD34(+) cells with MSC, TPO-expanded CD34(+) cells or TPO-expanded CD34(+) cells with MSC. We analyzed human platelet recovery in the peripheral blood (PB) from day 4 after transplantation onward and human bone marrow (BM) engraftment at week 6. The different transplants were assessed in vitro for their migration capacity and expression of CXCR4. TPO expansion improved the early platelet recovery in the PB of the mice. Cotransplantation of MSC with CD34(+) cells improved BM engraftment and platelet levels in the PB 6 weeks after transplantation. Combining TPO expansion and MSC cotransplantation, however, neither resulted in a more efficient early platelet recovery, nor in a better BM engraftment, nor even very low or absent BM engraftment occurred. In vitro, MSC boosted the migration of CD34(+) cells, suggesting a possible mechanism for the increase in engraftment. Our results show that cotransplantation of MSC with TPO-expanded CD34(+) cells at most combines, but does not increase the separate advantages of these different strategies. A combination of both strategies even adds a risk of non engraftment.
authors: 1Jon J van Rood Center for Clinical Transfusion Research, Sanquin Blood Supply Foundation, Leiden, the Netherlands.|2Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors: Mark
authors: M
authors: van der Garde
authors: 1Jon J van Rood Center for Clinical Transfusion Research, Sanquin Blood Supply Foundation, Leiden, the Netherlands.|2Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors: Anneke
authors: A
authors: Brand
authors: 1Jon J van Rood Center for Clinical Transfusion Research, Sanquin Blood Supply Foundation, Leiden, the Netherlands.
authors: Manon C
authors: MC
authors: Slot
authors: 1Jon J van Rood Center for Clinical Transfusion Research, Sanquin Blood Supply Foundation, Leiden, the Netherlands.
authors: Alice
authors: A
authors: de Graaf-Dijkstra
authors: 1Jon J van Rood Center for Clinical Transfusion Research, Sanquin Blood Supply Foundation, Leiden, the Netherlands.|2Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors: Jaap Jan
authors: JJ
authors: Zwaginga
authors: 1Jon J van Rood Center for Clinical Transfusion Research, Sanquin Blood Supply Foundation, Leiden, the Netherlands.
authors: Yvette
authors: Y
authors: van Hensbergen
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D036101:Cord Blood Stem Cell Transplantation; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D016513:Mice, SCID; D013926:Thrombopoietin / Q000008:administration & dosage*; D014183:Transplantation, Heterologous
chemical_list: D018952:Antigens, CD34; D013926:Thrombopoietin