Cord-Blood Engraftment with Ex Vivo Mesenchymal-Cell Coculture

From the Departments of Stem Cell Transplantation and Cellular Therapy (M.L., I. McNiece, S.N.R., A.A., R.S., I.K., P.K., S.P., U.P., C.H., R.C., J.J.M., R.B.J., Y.N., B.S.A., N.S., B.O., M.H.Q., M.K., G.R., S.C., D.B., I. Maewal, E.J.S.), Biostatistics (M.M.), and Pediatrics (L.J.N.C., L.W.), University of Texas M.D. Anderson Cancer Center, and the Center for Cell and Gene Therapy, Baylor College of Medicine (C.B.) - both in Houston
New England Journal of Medicine (Impact Factor: 55.87). 12/2012; 367(24):2305-2315. DOI: 10.1056/NEJMoa1207285
Source: PubMed


Poor engraftment due to low cell doses restricts the usefulness of umbilical-cord-blood transplantation. We hypothesized that engraftment would be improved by transplanting cord blood that was expanded ex vivo with mesenchymal stromal cells.

We studied engraftment results in 31 adults with hematologic cancers who received transplants of 2 cord-blood units, 1 of which contained cord blood that was expanded ex vivo in cocultures with allogeneic mesenchymal stromal cells. The results in these patients were compared with those in 80 historical controls who received 2 units of unmanipulated cord blood.

Coculture with mesenchymal stromal cells led to an expansion of total nucleated cells by a median factor of 12.2 and of CD34+ cells by a median factor of 30.1. With transplantation of 1 unit each of expanded and unmanipulated cord blood, patients received a median of 8.34×10(7) total nucleated cells per kilogram of body weight and 1.81×10(6) CD34+ cells per kilogram--doses higher than in our previous transplantations of 2 units of unmanipulated cord blood. In patients in whom engraftment occurred, the median time to neutrophil engraftment was 15 days in the recipients of expanded cord blood, as compared with 24 days in controls who received unmanipulated cord blood only (P<0.001); the median time to platelet engraftment was 42 days and 49 days, respectively (P=0.03). On day 26, the cumulative incidence of neutrophil engraftment was 88% with expansion versus 53% without expansion (P<0.001); on day 60, the cumulative incidence of platelet engraftment was 71% and 31%, respectively (P<0.001).

Transplantation of cord-blood cells expanded with mesenchymal stromal cells appeared to be safe and effective. Expanded cord blood in combination with unmanipulated cord blood significantly improved engraftment, as compared with unmanipulated cord blood only. (Funded by the National Cancer Institute and others; number, NCT00498316.).

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    • "BM engraftment of cord blood HSCs is also accelerated after inhibition of CD26/dipeptidylpeptidase IV (Campbell et al., 2007; Christopherson et al., 2007) and ex vivo fucosylation (Robinson et al., 2012). BMSCs cultured under standard adherent conditions have been shown to support the ex vivo expansion of hematopoietic progenitors (Breems et al., 1997; Harvey and Dzierzak, 2004; Sharma et al., 2011; Verfaillie, 1992) but may be insufficient to preserve primitive HSCs (de Lima et al., 2012). However, BMSCs are still retrospectively isolated based on their high plastic adherence and/or cultured in minimal medium supplemented with serum. "
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