Co-Transplantation of Ucbmn with UC-MSC Enhances Engraftment of Ucbmn in Iron Overload NOD/SCID Mice

Background: Umbilical cord blood (UCB)-derived hematopoietic stem cells (HSC) are ideal for allogeneic HSCT when a compatible donor is unavailable. However, the insufficient number of HSCs per UCB unit delays engraftment and may lead to graft failure and/or mortality. Besides, transfusion-induced iron overload has been reported to be involved in the delayed engraftment of HSC. Previously mesenchymal stem cells (MSC) have been implicated in playing a significant role in HSC engraftment. This study aimed to determine the effect of co-transplantation of umbilical cord mesenchymal stem cells (UC-MSC) on engraftment and hematopoietic recovery.

Methods: The iron overload NOD/SCID mice were induced by dose-escalation injection of iron dextran. And the sublethally irradiated iron overload NOD/SCID mice were divided into four groups: (1) intravenous injection of normal saline (control group, n=8), (2) intravenous injection of umbilical cord mesenchymal MN) alone (n=10), (3) intravenous injection of UCBMN and UC-MSC (n=10), and (4) intrafemoral injection of UCBMN and UC-MSC (n=12). Six weeks after injection of UC, the bone marrow (BM) was harvested and analyzed. The semi-quantitative analysis of cytokines including SDF-1a, OPN, and VEGF-α were examined by immunohistochemistry.

Results: As a result, iron deposits in bone liver, BM and spleen. In the BM of control group, no human CD45⁺ cells were found. Via the intra-bone marrow (iBM) injection, the percentage of human CD45⁺ cells was 9.86% ±1.86% (n=10) in the presence and 3.18% ±0.98% (n=6) in the absence of MSC, respectively, via the tail vein, the percentage of human CD45⁺ cells was 3.5%±0.94%. In additional, the levels of SDF-1a, OPN, and VEGF-a were all significantly higher in The mice that received MSC showed significantly enhanced engraftment in all three experiments (P=0.000).

Conclusion: Co-transplantation of UC-MSC is effective for improving engraftment in iron overload NOD/SCID mice. The point underlying the positive outcome may relate to cytokines including SDF-1a, OPN, and VEGF-a secreted by UC-MSC, which has been indicated to play a crucial part in homing and engraftment.