The Journal of Experimental Medicine
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Published 19 July 2004. doi:10.1084/jem.20040440
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 2, 123-135
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A New Human Somatic Stem Cell from Placental Cord Blood with Intrinsic Pluripotent Differentiation Potential

Gesine Kögler1, Sandra Sensken1, Judith A. Airey2, Thorsten Trapp1, Markus Müschen1, Niklas Feldhahn1, Stefanie Liedtke1, Rüdiger V. Sorg1, Johannes Fischer1, Claudia Rosenbaum3, Susanne Greschat3, Andreas Knipper1,4, Jörg Bender4, Özer Degistirici1,4, Jizong Gao5, Arnold I. Caplan5, Evan J. Colletti2, Graça Almeida-Porada6, Hans W. Müller3, Esmail Zanjani6, and Peter Wernet1

1 Institute for Transplantation Diagnostics and Cell Therapeutics, University of Düsseldorf Medical School, 40225 Düsseldorf, Germany
2 Department of Pharmacology, University of Nevada Medical School, Reno, NV 89523
3 Molecular Neurobiology Laboratory, Department of Neurology, University of Düsseldorf Medical School, 40225 Düsseldorf, Germany
4 Kourion Therapeutics, 40764 Langenfeld, Germany
5 Skeletal Research Center, Case Western Reserve University, Cleveland, OH 44106
6 Veterans Administration Medical Center, University of Nevada, Reno, NV 89557

Address correspondence to Gesine Kögler, Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich Heine University Medical Center, Moorenstrasse 5, Bldg. 14.80, 40225 Düsseldorf, Germany. Phone: 49-211-8116794. Fax: 49-211-8116792. email: koegler{at}itz.uni-duesseldorf.de

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 1015 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.

Key Words: cord blood • regenerative medicine • ex vivo expansion • developmental potential

Abbreviations used in this paper: ALP, alkaline phosphatase; CB, cord blood; DAG, dexomethasone, ascorbic acid, ß-glycerol phosphate; DAPI, 4-6'diamidino-2-phenylindoline; GABA, gamma amino butyric acid; GFAP, glial fibrillary acidic protein; hTau, human Tau protein; IBMX, isobuthyl methyl xanthine; MAPC, multipotent adult progenitor cell; MSC, mesenchymal stem cells; NF, neurofilament; NGF, nerve growth factor; NGS, normal goat serum; pd, population doubling; PFA, paraformaldehyde; TH, tyrosine-hydroxylase; USSC, unrestricted somatic stem cell.


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