Hepatocytes derived from peripheral blood stem cells of granulocyte-colony stimulating factor treated F344 rats in analbuminemic rat livers.
BACKGROUND
hematopoietic stem cells (SCs) mobilized from the bone marrow (BM) into peripheral blood (PB) are reported to have ability to differentiate into various cell types. We investigated whether PB-SCs mobilized by treatment with granulocyte-colony stimulating factor (G-CSF) in normal rats can raise albumin-producing hepatocytes after transplantation within the liver of analbuminemic rats.


METHODS
Fischer 344 rats (F344) were used as donors, and F344 congenic Nagase's analbuminemic rats (F344alb) as recipients. The donors were repeatedly treated with human recombinant G-CSF, and their PB mononuclear cells (MNCs) were infused into the portal veins of recipients immediately after 70% hepatectomy (PH).


RESULTS
Although a few single and small clusters (less than five cells) of albumin positive (alb+) hepatocytes were seen in the livers of untreated F344alb and of the animals undergoing PH alone or transplantation of PB-MNCs with or without the prior G-CSF treatment, clusters consisting of more than 6 alb+ hepatocytes were only detected in the livers of recipients that received transplantation of mobilized PB-MNCs or BM-MNCs under the regenerating condition induced by PH. Sry3, a Y chromosome marker, could be detected corresponding to the alb+ clusters by in situ hybridization when male donors and female recipients were used. Moreover, normal albumin gene sequences were demonstrated in the microdissected alb+ clusters by polymerase chain reaction, and the serum albumin levels were elevated in the recipients.


CONCLUSIONS
Hematopoietic SCs mobilized from BM into PB by the G-CSF treatment may raise hepatocyte colonies, when transplanted into regenerating livers.
Huiling
Xiang
X
Department of Surgery, Asahikawa Medical College, Midorigaoka-Higashi, Asahikawa, Japan. Huilingxiang@sohu.com
Inagaki
Mitsuhiro
M
Arikura
Jun
J
Ozaki
Atsuko
A
Onodera
Kazuhiko
K
Ogawa
Katsuhiro
K
Kasai
Shinichi
S
D000818:Animals; D001796:Blood Protein Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D002454:Cell Differentiation; D002465:Cell Movement; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology*; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008099:Liver / Q000473:pathology / Q000601:surgery*; D008297:Male; D009000:Monocytes / Q000637:transplantation*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000494:pharmacology; D012709:Serum Albumin / Q000096:biosynthesis / Q000172:deficiency*
D012333:RNA, Messenger; D011994:Recombinant Proteins; D012709:Serum Albumin; D016179:Granulocyte Colony-Stimulating Factor