Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2134961 | Experimental Hematology | 2008 | 9 Pages |
ObjectiveDelayed platelet recovery post–cord blood (CB) transplantation might be due to CB characteristics: low maturity of stem cell compartment, poor production of CD34+/CD41+ cells when induced to differentiate along the megakaryocytic (MK) lineage, retention of a low ploidy in the expanded MKs. Ex vivo expansion of CB hematopoietic progenitor cells for reconstitution of different human hematopoietic lineages has already been developed in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. However, optimal conditions for MK–progenitor engraftment to reduce hemorrhaging risk still to be developed. This study assesses the hypothesis that CB–CD34+ amplification with thrombopoietin (TPO) can be applied to a portion of a CB transplant unit to stimulate recovery along MK differentiation program.Materials and MethodsHuman CB–CD34+ cells were amplified in a serum–free, clinical grade medium with 100 ng/mL TPO alone and in addition to other cytokines (Kit ligand, interleukin–6, and Flt–3 ligand). Seven–day cultured cells were transplanted into irradiated NOD/SCID mice and engraftment, megakaryocytopoiesis, and platelet production were assessed.ResultsPlatelet release was successful and continuously present for at least 8 weeks in NOD/SCID mice transplanted with CB cells stimulated by TPO. Thrombocytopoiesis was more effective with transplanted TPO–amplified cells than with the cytokine cocktails.ConclusionPlatelet number obtained is within the minimum level considered sufficient for hemostasis. Furthermore, amplified cells maintain their self–renewal capacity and multilineage potential differentiation. Thus, transplantation of TPO–expanded CB cells has the potential favoring both platelet recovery and human engraftment.