A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential.
Here a new, intrinsically pluripotent, CD45-negative population from human cord blood, termed unrestricted somatic stem cells (USSCs) is described. This rare population grows adherently and can be expanded to 10(15) cells without losing pluripotency. In vitro USSCs showed homogeneous differentiation into osteoblasts, chondroblasts, adipocytes, and hematopoietic and neural cells including astrocytes and neurons that express neurofilament, sodium channel protein, and various neurotransmitter phenotypes. Stereotactic implantation of USSCs into intact adult rat brain revealed that human Tau-positive cells persisted for up to 3 mo and showed migratory activity and a typical neuron-like morphology. In vivo differentiation of USSCs along mesodermal and endodermal pathways was demonstrated in animal models. Bony reconstitution was observed after transplantation of USSC-loaded calcium phosphate cylinders in nude rat femurs. Chondrogenesis occurred after transplanting cell-loaded gelfoam sponges into nude mice. Transplantation of USSCs in a noninjury model, the preimmune fetal sheep, resulted in up to 5% human hematopoietic engraftment. More than 20% albumin-producing human parenchymal hepatic cells with absence of cell fusion and substantial numbers of human cardiomyocytes in both atria and ventricles of the sheep heart were detected many months after USSC transplantation. No tumor formation was observed in any of these animals.
Kögler
Gesine
G
Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich Heine University Medical Center, Moorenstrasse 5, 40225 Düsseldorf, Germany. koegler@itz.uni-duesseldorf.de
Sensken
Sandra
S
Airey
Judith A
JA
Trapp
Thorsten
T
Müschen
Markus
M
Feldhahn
Niklas
N
Liedtke
Stefanie
S
Sorg
Rüdiger V
RV
Fischer
Johannes
J
Rosenbaum
Claudia
C
Greschat
Susanne
S
Knipper
Andreas
A
Bender
Jörg
J
Degistirici
Ozer
O
Gao
Jizong
J
Caplan
Arnold I
AI
Colletti
Evan J
EJ
Almeida-Porada
Graça
G
Müller
Hans W
HW
Zanjani
Esmail
E
Wernet
Peter
P
D017667:Adipocytes / Q000166:cytology; D000418:Albumins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001842:Bone and Bones / Q000166:cytology; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D017690:Cell Transplantation; D036101:Cord Blood Stem Cell Transplantation; D005269:Femur / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology*; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000378:metabolism; D018377:Neurotransmitter Agents; D010006:Osteoblasts / Q000378:metabolism; D010641:Phenotype; D010920:Placenta / Q000098:blood supply*; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors; D014471:Umbilical Veins
D000418:Albumins; D018377:Neurotransmitter Agents; D017493:Leukocyte Common Antigens