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How to Improve Cord Blood Engraftment?

ABSTRACT: Various factors make cord blood (CB) a significant source of hematopoietic stem cells (HSCs), including ease of procurement and lack of donor attrition, with the ability to process and store the donor cells long term. Importantly, high proliferative potential of the immature HSCs allows one log less use of cells compared to bone marrow or peripheral blood stem cells. As total nucleated cell (TNC) and CD34(+) cell content of CB grafts are correlated to engraftment rate and speed, strategies to expand HSC and homing have been developed. This chapter will focus only on modalities such as intrabone administration, fucosylation, CD26 inhibition, prostaglandin E2 derivative or complement 3 exposure, and SDF-1/CXCR4/CXCL-12 pathway interventions that have been experimented successfully. Furthermore, increasing evidence in line with better recognition of CB progenitors that are involved in engraftment and homing will also be addressed.

SUBMITTER: Beksac M

PROVIDER: S-EPMC4756107 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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How to Improve Cord Blood Engraftment?

Beksac Meral M Yurdakul Pinar P

Frontiers in medicine 20160217

Various factors make cord blood (CB) a significant source of hematopoietic stem cells (HSCs), including ease of procurement and lack of donor attrition, with the ability to process and store the donor cells long term. Importantly, high proliferative potential of the immature HSCs allows one log less use of cells compared to bone marrow or peripheral blood stem cells. As total nucleated cell (TNC) and CD34(+) cell content of CB grafts are correlated to engraftment rate and speed, strategies to ex ...[more]

PMID: 26925402

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Project description:BackgroundPoor 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.MethodsWe 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.ResultsCoculture 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).ConclusionsTransplantation 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; ClinicalTrials.gov number, NCT00498316.).

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How to Improve Cord Blood Engraftment?

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How to Improve Cord Blood Engraftment?

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