Intra-osseous Co-transplantation of CD34-selected Umbilical Cord Blood and Mesenchymal Stromal Cells.

Leland Metheny Iii,Alex Y Huang,Howard Meyerson,Saada Eid,Alexander Tong,Karen Lingas,Marcos De Lima,Jane Reese

doi:10.15761/hmo.1000105

Abstract

Human mesenchymal stromal cells (MSC) have been shown to support the growth and differentiation of hematopoietic stem cells (HSC). We hypothesized that intra-osseous (IO) co-transplantation of MSC and umbilical cord blood (UCB) may be effective in improving early HSC engraftment, as IO transplantation has been demonstrated to enhance UCB engraftment in NOD SCID-gamma (NSG) mice. Following non-lethal irradiation (300rads), 6 groups of NSG mice were studied: 1) intravenous (IV) UCB CD34+ cells, 2) IV UCB CD34+ cells and MSC, 3) IO UCB CD34+ cells, 4) IO UCB CD34+ cells and IO MSC, 5) IO UCB CD34+ cells and IV MSC, and 6) IV UCB CD34+ and IO MSC. Analysis of human-derived CD45+, CD3+, and CD19+ cells 6 weeks following transplant revealed the highest level of engraftment in the IO UCB plus IO MSC cohort. Bone marrow analysis of human CD13 and CD14 markers revealed no significant difference between cohorts. We observed that IO MSC and UCB co-transplantation led to superior engraftment of CD45+, CD3+ and CD19+ lineage cells in the bone marrow at 6 weeks as compared with the IV UCB cohort controls. Our data suggests that IO co-transplantation of MSC and UCB facilitates human HSC engraftment in NSG mice.

Highlights

Umbilical cord blood (UCB) is rich in hematopoietic stem cells (HSC) and it has been used as a graft source for both hematopoietic stem cell transplant (SCT) patients and murine models of transplant [1,2]
Cellular engraftment was significantly enhanced in the group receiving the IO co-transplantation of UCB and mesenchymal stromal cells (MSC) as compared to IV UCB alone (34% vs. 2.9%, respectively; Figure 1 and Table 1; p < 0.001)
Consistent with our hypothesis that administration of MSC improves overall UCB engraftment, we observed that any combination of UCB and MSC coadministration, irrespective of the mode of delivery of either the UCB or MSC, exhibited significantly improved HSC engraftment as compared to IV UCB injection alone

Summary

Introduction

Umbilical cord blood (UCB) is rich in hematopoietic stem cells (HSC) and it has been used as a graft source for both hematopoietic stem cell transplant (SCT) patients and murine models of transplant [1,2]. Due to delayed or sub-optimal engraftment in both mice and humans, other methods beyond IV infusion have been proposed. These include intra-osseous infusion, co-infusion of the UCB with mesenchymal stromal cells (MSC), or ex vivo expansion of UCB prior to infusion [3,4,5]. We report our data on intra-osseous co-infusion of UCB and MSC in a murine model of transplant. Cui et al demonstrated that when fluorescently labelled donor bone marrow cells are injected IV in an irradiated syngeneic mouse model, only 1-2% of donor HSCs reached the bone marrow [6].

Methods

Results

Conclusion