Release from quiescence of CD34+ CD38- human umbilical cord blood cells reveals their potentiality to engraft adults.
Using optimal culture conditions in which the transforming growth factor beta 1 (TGF-beta 1) inhibitory loop has been interrupted by antisense TGF-beta 1 oligonucleotides or anti-TGF-beta serum, we have compared the proliferative capacities and the abilities of the CD34+ CD38- cell populations from bone marrow and umbilical cord blood to generate early progenitors in long-term cultures. The CD34+ CD38- fraction of umbilical cord blood accounts for 4% of the CD34+ fraction compared to only 1% in bone marrow, indicating that umbilical cord blood may be relatively enriched in stem cells. We estimate that the CD34+ CD38- cells from a typical umbilical cord blood sample produce equivalent numbers of colony-forming units (CFU)-granulocyte/erythrocyte/macrophage/megakaryocyte, twice as many CFU-granulocyte/macrophage (GM) and 3 times as many burst-forming units-erythroid as the same population from an average bone marrow sample used in adult transplantation. In addition, the colonies resulting from the umbilical cord blood samples were significantly larger than those from bone marrow, indicating a greater growth potential. However, the content of later progenitors, which may be important for short-term reconstitution, was less in umbilical cord blood-derived than in bone marrow-derived cell preparations, as estimated by a 4-fold lower production of CFU-GM in long-term cultures of CD34+ CD38+ cells. This deficit is partially compensated by the higher growth capacity of the resulting CFU-GM. These studies suggest that umbilical cord blood is a suitable source of cells for adult transplantation.
Cardoso
A A
AA
Centre National de la Recherche Scientifique UPR 272, Villejuif, France.
Li
M L
ML
Batard
P
P
Hatzfeld
A
A
Brown
E L
EL
Levesque
J P
JP
Sookdeo
H
H
Panterne
B
B
Sansilvestri
P
P
Clark
S C
SC
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D015703:Antigens, CD / Q000097:blood*; D018952:Antigens, CD34; D000943:Antigens, Differentiation / Q000097:blood*; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology; D006133:Growth Substances / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology
D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D006133:Growth Substances; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1