Characterization and clinical application of human CD34+ stem/progenitor cell populations mobilized into the blood by granulocyte colony-stimulating factor.
A phase I study was performed to determine the safety and tolerability of injecting autologous CD34(+) cells into five patients with liver insufficiency. The study was based on the hypothesis that the CD34(+) cell population in granulocyte colony-stimulating factor (G-CSF)-mobilized blood contains a subpopulation of cells with the potential for regenerating damaged tissue. We separated a candidate CD34(+) stem cell population from the majority of the CD34(+) cells (99%) by adherence to tissue culture plastic. The adherent and nonadherent CD34(+) cells were distinct in morphology, immunophenotype, and gene expression profile. Reverse transcription-polymerase chain reaction-based gene expression analysis indicated that the adherent CD34(+) cells had the potential to express determinants consistent with liver, pancreas, heart, muscle, and nerve cell differentiation as well as hematopoiesis. Overall, the characteristics of the adherent CD34(+) cells identify them as a separate putative stem/progenitor cell population. In culture, they produced a population of cells exhibiting diverse morphologies and expressing genes corresponding to multiple tissue types. Encouraged by this evidence that the CD34(+) cell population contains cells with the potential to form hepatocyte-like cells, we gave G-CSF to five patients with liver insufficiency to mobilize their stem cells for collection by leukapheresis. Between 1 x 10(6) and 2 x 10(8) CD34(+) cells were injected into the portal vein (three patients) or hepatic artery (two patients). No complications or specific side effects related to the procedure were observed. Three of the five patients showed improvement in serum bilirubin and four of five in serum albumin. These observations warrant further clinical trials.
Faculty of Medicine, Imperial College London, Hammersmith Campus, UK.
Myrtle Y
MY
Gordon
Natasa
N
Levicar
Madhava
M
Pai
Philippe
P
Bachellier
Ioannis
I
Dimarakis
Faisal
F
Al-Allaf
Hanane
H
M'Hamdi
Tamara
T
Thalji
Jonathan P
JP
Welsh
Stephen B
SB
Marley
John
J
Davies
Francesco
F
Dazzi
Federica
F
Marelli-Berg
Paul
P
Tait
Raymond
R
Playford
Long
L
Jiao
Steen
S
Jensen
Joanna P
JP
Nicholls
Ahmet
A
Ayav
Mahrokh
M
Nohandani
Farzin
F
Farzaneh
Joop
J
Gaken
Rikke
R
Dodge
Malcolm
M
Alison
Jane F
JF
Apperley
Robert
R
Lechler
Nagy A
NA
Habib
D018952:Antigens, CD34 / Q000097:blood / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood* / Q000378:metabolism*; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000628:therapy; D008109:Liver Diseases, Parasitic / Q000628:therapy; D008297:Male; D008875:Middle Aged; D039902:Multipotent Stem Cells / Q000378:metabolism
D018952:Antigens, CD34; D016179:Granulocyte Colony-Stimulating Factor