Cotransplantation of MSCs and HSCs.

Apilot study by Wu et al. (1) suggests that umbilical cordYderived mesenchymal stem cells (UCMSCs) promote hematopoietic engraftment when cotransplanted with cord blood (CB) cells (Fig. 1A). The authors make good use of two somatic stem cells, both derived from umbilical cord. Together with the establishment of their UCMSC bank, their trial appears to be potentially meaningful for future development of UCMSC cotransplantation. A recent article by de Lima et al. (2) demonstrates that hematopoietic engraftment is improved by transplantation of CB cells that are expanded ex vivo with allogeneic bone marrowYderived MSCs (BMMSCs). In this study (2), two CB units were transplanted: one was an expanded CB unit and the other was an unmanipulated CB unit (Fig. 1B). Although BMMSCs were used ex vivo only (2), expanded CB in combination with unmanipulated CB significantly improved engraftment compared with unmanipulated CB only. Based on these findings, it would be interesting to investigate whether addition of ex vivo expanded CB to the pilot study setting by Wu et al. (1) would further improve engraftment (Fig. 1C). The study by de Lima et al. (2) appears to be safe and effective, because ex vivo expanded CB unit would contribute to rapid recovery of hematopoiesis. However, this study raises some concerns. (i) CB was expanded under culture condition with cytokines including granulocyte colony-stimulating factor, which would expand myeloid progenitor cells at the expense of longterm hematopoietic stem cells (LT-HSCs) (Fig. 1B). Because long-term repopulation has been shown to be dependent on unmanipulated CB, there might be a longterm risk of cytopenia. (ii) Due to reduced percentage of lymphocytes in expanded CB described by de Lima et al. (2), there might be an increased risk of viral infection. Regarding (i), recent evidence suggests that in vitro maintenance of LT-HSCs is possible by dual inhibition (2i) of both glycogen synthase kinase-3 and mammalian target of rapamycin, without use of cytokines that promote differentiation of LT-HSCs (3). Although LT-HSCs were shown to be preserved