We found that UCMSC had superior proliferative potential and more suppressive effects on peripheral blood mononuclear cell proliferation compared with BMMSC. The aGVHD improved dramatically after each of four infusions of UCMSC into the two patients. No adverse effects were noted. Both patients are doing well now. CONCLUSIONS. Considering that acquiring UCMSC is noninvasive, these cells would appear to be the ideal candidates for clinical cell-based therapies. This is the first report of UCMSC in a human clinical application, and this procedure seems both feasible and safe. These findings suggested that UCMSC were effective for treating aGVHD.

Delayed hematopoietic reconstitution after cord blood (CB) transplantation (CBT) needs to be overcome. Bone marrow-derived mesenchymal stem cells (BMMSCs) have been found to enhance engraftment after hematopoietic stem cell transplantation. However, getting BMMSCs involves an invasive procedure. In this study, umbilical cord-derived mesenchymal stem cells (UCMSCs) were isolated from Wharton's jelly and cryopreserved in the UCMSCs bank. Compared with BMMSCs, we found that UCMSCs had superior proliferative potential. We found that NOD/SCID mice cotransplanted with CB and UCMSCs demonstrated significant human CD45(+) cell engraftment compared with those transplanted with CB alone. Then, 20 patients with high-risk leukemia were prospectively randomized to either receive cotransplantation of CB and ex vivo expanded banked UCMSCs or to receive CBT alone. No serious adverse events were observed in the patients receiving UCMSC infusion. The time to undergo neutrophil engraftment and platelet engraftment was significantly shorter in the eight patients receiving cotransplantation than that in the 12 patients receiving CBT alone (p=0.003 and p=0.004, respectively). Thus, application of ex vivo expanded banked UCMSCs in humans appears to be feasible and safe. UCMSCs can enhance engraftment after CBT, but further studies are warranted.

This pilot study is the first report of cotransplantation of UCMSCs in CBT. Intravenous infusion of UCMSCs appeared to be a feasible and safe modality to enhance hematopoietic engraftment in patients receiving CBT. Further studies were warranted.

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Hematopoietic stem cell transplantation (HSCT) is becoming an effective therapeutic modality for a variety of diseases. Mesenchymal stem cells (MSCs) can be used to enhance hematopoietic engraftment, accelerate lymphocyte recovery, reduce the risk of graft failure, prevent and treat graft-versus-host disease, and repair tissue damage in patients receiving HSCT. Till now, most MSCs for human clinical application have been derived from bone marrow. However, acquiring bone-marrow-derived MSCs involves an invasive procedure. Umbilical cord is rich with MSCs. Compared to bone-marrow-derived MSCs, umbilical cord-derived MSCs (UCMSCs) are easier to obtain without harm to the donor and can proliferate faster. No severe adverse effects were noted in our previous clinical application of UCMSCs in HSCT. Accordingly, application of UCMSCs in humans appears to be feasible and safe. Further studies are warranted.