Ex vivo expansion of cord blood-CD34(+) cells using IGFBP2 and Angptl-5 impairs short-term lymphoid repopulation in vivo.

ABSTRACT

Cord blood-derived haematopoietic stem cells (CB-HSCs) are an attractive source for transplantation in haematopoietic disorders. However, the yield of CB-HSCs per graft is limited and often insufficient, particularly for the treatment of adult patients. Here we compare the capacity of three cytokine cocktails to expand CB-CD34(+) cells. Cells were cultured for 5 or 14 days in media supplemented with (a) SCF, FL, IL-3 and IL-6 (SFLIL3/6); (b) SCF, TPO, FGF-1 and IL-6 (STFIL6); and (c) SCF, TPO, FGF-1, IGFBP2 and Angptl-5 (STFAI). We observed that STFAI-culture expansion sustained the most vigorous cell proliferation, maintenance of CD34(+) phenotype and colony-forming unit counts. In addition, STFAI-cultured cells had a potent ex vivo migration activity. STFAI-expanded cells were able to engraft NSG mice. However, no significant difference in overall engraftment was observed among the expansion cocktails. Assessment of short-term reconstitution using multilineage markers demonstrated that the STFAI cocktail for HSCs expansion greatly improved total cell expansion but may impair short-term lymphoid repopulation.