Transplanted human cord blood cells generate amylase-producing pancreatic acinar cells in engrafted mice.
OBJECTIVE
Pancreatic acinar cells and hepatocytes arise from the same cell population located within the embryonic endoderm. It has been reported that a multipotent population of liver cells is capable of differentiating into pancreatic cells. Recent studies revealed that murine and human hematopoietic cells could generate hepatocytes in vivo. Based on this developmental proximity between liver and pancreatic acinar cells, we examined whether human cord blood (CB) cells can generate pancreatic cells in vivo using a murine xenograft model.


METHODS
We transplanted 1 x 10 CD34 human CB cells into "conditioned" newborn nonobese diabetic-severe combined immunodeficiency/beta-2 microglobulin-null mice via facial vein injection and, 3 to 4 months later, examined the pancreata from recipient mice showing high-level human multilineage hematopoietic engraftment in the bone marrow.


RESULTS
Reverse transcriptase-polymerase chain reaction and immunohistochemical analyses revealed human amylase mRNA and protein expression, respectively, in the pancreata from recipient mice. Using fluorescence in situ hybridization, we identified human alpha-satellite, DNA-positive cells with a morphology characteristic of pancreatic acinar cells. We also identified cells in paraffin sections of the pancreata that expressed amylase mRNA, had morphological characteristics of acinar cells, and contained human but not mouse centromeric DNA.


CONCLUSIONS
These findings establish that human umbilical CB cells are capable of generating pancreatic acinar cells via a nonfusion mechanism.
Minamiguchi
Hitoshi
H
Department of Veterans Affairs Medical Center and Department of Medicine, Medical University of South Carolina, Charleston, SC, USA.
Ishikawa
Fumihiko
F
Fleming
Paul A
PA
Yang
Su
S
Drake
Christopher J
CJ
Wingard
John R
JR
Ogawa
Makio
M
D000681:Amylases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D018952:Antigens, CD34 / Q000032:analysis; D002454:Cell Differentiation; D048430:Cell Shape; D036101:Cord Blood Stem Cell Transplantation; D004276:DNA, Satellite / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology* / Q000201:enzymology / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D046790:Pancreas, Exocrine / Q000166:cytology* / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000201:enzymology / Q000276:immunology; D013997:Time Factors; D014183:Transplantation, Heterologous; D001613:beta 2-Microglobulin / Q000235:genetics / Q000378:metabolism
D018952:Antigens, CD34; D004276:DNA, Satellite; D012333:RNA, Messenger; D001613:beta 2-Microglobulin; D000681:Amylases