title: Direct Comparison of Wharton's Jelly and Bone Marrow-Derived Mesenchymal Stromal Cells to Enhance Engraftment of Cord Blood CD34(+) Transplants.
abstract: Cotransplantation of CD34(+) hematopoietic stem and progenitor cells (HSPCs) with mesenchymal stromal cells (MSCs) enhances HSPC engraftment. For these applications, MSCs are mostly obtained from bone marrow (BM). However, MSCs can also be isolated from the Wharton's jelly (WJ) of the human umbilical cord. This source, regarded to be a waste product, enables a relatively low-cost MSC acquisition without any burden to the donor. In this study, we evaluated the ability of WJ MSCs to enhance HSPC engraftment. First, we compared cultured human WJ MSCs with human BM-derived MSCs (BM MSCs) for in vitro marker expression, immunomodulatory capacity, and differentiation into three mesenchymal lineages. Although we confirmed that WJ MSCs have a more restricted differentiation capacity, both WJ MSCs and BM MSCs expressed similar levels of surface markers and exhibited similar immune inhibitory capacities. Most importantly, cotransplantation of either WJ MSCs or BM MSCs with CB CD34(+) cells into NOD SCID mice showed similar enhanced recovery of human platelets and CD45(+) cells in the peripheral blood and a 3-fold higher engraftment in the BM, blood, and spleen 6 weeks after transplantation when compared to transplantation of CD34(+) cells alone. Upon coincubation, both MSC sources increased the expression of adhesion molecules on CD34(+) cells, although stromal cell-derived factor-1 (SDF-1)-induced migration of CD34(+) cells remained unaltered. Interestingly, there was an increase in CFU-GEMM when CB CD34(+) cells were cultured on monolayers of WJ MSCs in the presence of exogenous thrombopoietin, and an increase in BFU-E when BM MSCs replaced WJ MSCs in such cultures. Our results suggest that WJ MSC is likely to be a practical alternative for BM MSC to enhance CB CD34(+) cell engraftment.
authors.affiliation: 1 Jon J van Rood Center for Clinical Transfusion Research , Sanquin Blood Supply Foundation, Leiden, the Netherlands .|2 Department of Immunohematology and Blood Transfusion, Leiden University Medical Center , Leiden, the Netherlands .|3 Stem Cell Research, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford , and NHS Blood and Transplant Oxford, Oxford, United Kingdom .
authors.forename: Mark
authors.initials: M
authors.lastname: van der Garde
authors.affiliation: 2 Department of Immunohematology and Blood Transfusion, Leiden University Medical Center , Leiden, the Netherlands .
authors.forename: Melissa
authors.initials: M
authors.lastname: van Pel
authors.affiliation: 1 Jon J van Rood Center for Clinical Transfusion Research , Sanquin Blood Supply Foundation, Leiden, the Netherlands .|2 Department of Immunohematology and Blood Transfusion, Leiden University Medical Center , Leiden, the Netherlands .
authors.forename: Jose Eduardo
authors.initials: JE
authors.lastname: Millán Rivero
authors.affiliation: 1 Jon J van Rood Center for Clinical Transfusion Research , Sanquin Blood Supply Foundation, Leiden, the Netherlands .
authors.forename: Alice
authors.initials: A
authors.lastname: de Graaf-Dijkstra
authors.affiliation: 1 Jon J van Rood Center for Clinical Transfusion Research , Sanquin Blood Supply Foundation, Leiden, the Netherlands .
authors.forename: Manon C
authors.initials: MC
authors.lastname: Slot
authors.affiliation: 1 Jon J van Rood Center for Clinical Transfusion Research , Sanquin Blood Supply Foundation, Leiden, the Netherlands .
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kleinveld
authors.affiliation: 3 Stem Cell Research, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford , and NHS Blood and Transplant Oxford, Oxford, United Kingdom .
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Watt
authors.affiliation: 2 Department of Immunohematology and Blood Transfusion, Leiden University Medical Center , Leiden, the Netherlands .
authors.forename: Helene
authors.initials: H
authors.lastname: Roelofs
authors.affiliation: 1 Jon J van Rood Center for Clinical Transfusion Research , Sanquin Blood Supply Foundation, Leiden, the Netherlands .|2 Department of Immunohematology and Blood Transfusion, Leiden University Medical Center , Leiden, the Netherlands .
authors.forename: Jaap Jan
authors.initials: JJ
authors.lastname: Zwaginga
mesh_terms: D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D018952:Antigens, CD34