Ex vivo expansion of cord blood-CD34(+) cells using IGFBP2 and Angptl-5 impairs short-term lymphoid repopulation in vivo.
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.
Institute of Pathology, RWTH Aachen University, Germany.
Mónica S
MS
Ventura Ferreira
Norina
N
Labude
Gudrun
G
Walenda
Carina
C
Adamzyk
Wolfgang
W
Wagner
Daniela
D
Piroth
Albrecht M
AM
Müller
Ruth
R
Knüchel
Thomas
T
Hieronymus
Martin
M
Zenke
Willi
W
Jahnen-Dechent
Sabine
S
Neuss
D042682:Angiopoietins / Q000494:pharmacology*; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002999:Clone Cells; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000494:pharmacology; D005312:Fetal Blood / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000494:pharmacology*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013154:Spleen / Q000166:cytology; D019089:Stem Cell Factor / Q000494:pharmacology; D013926:Thrombopoietin / Q000494:pharmacology
D042682:Angiopoietins; D018952:Antigens, CD34; D016207:Cytokines; D018971:Insulin-Like Growth Factor Binding Protein 2; D019089:Stem Cell Factor; D013926:Thrombopoietin; D017493:Leukocyte Common Antigens