Ex vivoexpansion of cord blood-CD34+cells using IGFBP2and Angptl-5 impairs short-term lymphoid repopulationin vivo

Autor: Martin Zenke, Carina Adamzyk, Ruth Knüchel, Thomas Hieronymus, Mónica S. Ventura Ferreira, Wolfgang Wagner, Albrecht M. Müller, Sabine Neuss, Norina Labude, Gudrun Walenda, Willi Jahnen-Dechent, Daniela Piroth
Rok vydání: 2012
Předmět:
Zdroj: Journal of Tissue Engineering and Regenerative Medicine. 7:944-954
ISSN: 1932-6254
DOI: 10.1002/term.1486
Popis: 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. Copyright © 2012 John Wiley & Sons, Ltd.
Databáze: OpenAIRE