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PMID: 15263023 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential.

The Journal of experimental medicine ·Vol. 200 ·No. 2 ·2004-07-19 ·Pages 123-35

Kögler G, Sensken S, Airey JA, Trapp T, Müschen M, Feldhahn N, Liedtke S, Sorg RV, Fischer J, Rosenbaum C, Greschat S, Knipper A, Bender J, Degistirici O, Gao J, Caplan AI, Colletti EJ, Almeida-Porada G, Müller HW, Zanjani E, Wernet P

Abstract

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.

MeSH Terms
Adipocytes/cytology Albumins/metabolism Animals Blotting, Western Bone and Bones/cytology Cell Culture Techniques Cell Differentiation Cell Division Cell Line Cell Transplantation Cord Blood Stem Cell Transplantation Femur/metabolism Fetal Blood/cytology Flow Cytometry Gene Expression Regulation, Developmental Hematopoietic Stem Cells/cytology Hippocampus/cytology Humans Immunophenotyping Leukocyte Common Antigens/biosynthesis Leukocytes, Mononuclear/metabolism Myocardium/cytology Myocytes, Cardiac/metabolism Neurotransmitter Agents Osteoblasts/metabolism Phenotype Placenta/blood supply Polymerase Chain Reaction Rats Rats, Wistar Reverse Transcriptase Polymerase Chain Reaction Sheep Stem Cells/cytology Time Factors Umbilical Veins
Chemicals
Albumins Neurotransmitter Agents Leukocyte Common Antigens
Authors & Affiliations
21 authors, click to expand affiliations / ORCID
Kögler Gesine
Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich Heine University Medical Center, Moorenstrasse 5, 40225 Düsseldorf, Germany. koegler@itz.uni-duesseldorf.de
Sensken Sandra
Airey Judith A
Trapp Thorsten
Müschen Markus
Feldhahn Niklas
Liedtke Stefanie
Sorg Rüdiger V
Fischer Johannes
Rosenbaum Claudia
Greschat Susanne
Knipper Andreas
Bender Jörg
Degistirici Ozer
Gao Jizong
Caplan Arnold I
Colletti Evan J
Almeida-Porada Graça
Müller Hans W
Zanjani Esmail
Wernet Peter
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
Published
2004-07-19
Pages
123-35
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2212008
Subset
IM
Grants
NIAMS NIH HHS · R01 AR045112 · United States
NHLBI NIH HHS · R01 HL077976 · United States
NIAMS NIH HHS · AR45112 · United States
NHLBI NIH HHS · HL077976 · United States
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