Unrestricted Somatic Stem Cells (USSC) from Umbilical Cord Blood

 
Project Z
Generation and Functional Characterization of Differentiation Pathways of USSC

 
Summary        Members        Project goals       Collaborations      Other     Back to mainpage
 

Summary

This project will supply USSC generated in bulk or on a clonal level as well as read-out systems for the Research Group.
To ascertain consistency and comparability of USSC, controls will be performed, confirming differentiation potential, immunophenotype and expansion capacity.
Studies on homogeneity of USSC will be extended to identify possible subpopulations and to delineate a possible stem cell hierarchy.

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Members

Founded researchers
Prof. Dr. Gesine Kögler
 		 Leader
Director of The José Carreras Cord Blood Bank and The Cell Processing Laboratory of the Institute for Transplantation Diagnostics and Cellular Therapeutics at the Medical School of the University of Düsseldorf
Dr. Anja Buchheiser
 PostDoc
Project coordinator and supervisor; cell and molecular biology specialist
Simone Maria Kluth
 Ph.D. student
Adipose differentiation; immunohistochemistry
Simon Waclawczyk
 Ph.D. student
Endodermal differentiation; factors of liver and pancreatic development
Daniela Stapelkamp
 Technical assistant
Cell culture and endodermal differentiation; Western blot specialist
Aurélie Lefort
 Technical assistant
Cell culture; GMP-conform USSC generation and quality control
Affiliates
Dr. Stefanie Liedtke
 PostDoc
Secondary project coordinator and supervisor; molecular biology specialist
Teja Falk Radke
 Ph.D. student
Haematopoiesis-supporting capacities of USSC; FACS-analysis
Amelie Houben
 Ph.D. student
Analysis of telomere length and telomerase activity in USSC and MSC
Julia Bosch
 Ph.D. student
Influence of hypoxic conditions on the generation and the development of stromal cells
Stefanie Geyh
 Ph.D. student
Generation of clonal cell lines
Associates
Dr. Rüdiger V. Sorg
 Ph.D.
Immunotherapy
Dr. Thorsten Trapp
 Ph.D.
Molecular neuropathology
Marat Fudim
 Medical doctor candiate





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Project goals

- Generation, expansion and providing of quality controlled USSC


- Generation and providing USSC clones and genetically marked cells


- Providing read-out systems for differentiation potential of manipulated USSC










Supplemental tasks :

 - Optimization of USSC generation and expansion

 - Development of tools to further assess USSC homogeneity

 - Quantification and functional confirmation of osteogenic, neural and endodermal differentiation of USSC

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Collaborations

DFG-project collaboration partners:
Project Z will provide all other projects with cells / read-out systems and receive feedback from all other projects on performance of cells :

A1: Developmental potential of USSC

A2: Evaluation of neural differentiation

A3: Reprogramming and dedifferentiation of USSC

A4: microRNAs, transcription factors, novel markers

A5: Evaluation of epigenetic profiles
National collaboration partners:
Current collaborations :

A. Ruhparwar
 Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany

 J. Zeller
 German Cancer Research Center (DKFZ), Heidelberg, Germany

H. Hanenberg
 Clinic for Pediatric Oncology, Hematology and Clinical Immunology, University Hospital, Duesseldorf, Germany

J.G. Hengstler
 Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany
B. Brand-Saberi
 Institute of Anatomy and Cell Biology, Department of Molecular Embryology, Ruhr-University of Bochum,  Bochum, Germany
 (Formerly Institute of Anatomy and Cell Biology, University of Freiburg, Freiburg, Germany)

U. Flögel
 Inst. for Cardiovascular Physiology, HHU Düsseldorf
International collaboration partners:

Current collaborations :

P. Bianco
 Department of experimental medicine and pathology, La Sapienza University of Rome, Rome, Italy
(Separate DFG-Bilateral Event "DLK-1 As A Marker To Define The Hierarchy Of Neonatal And Adult Mesenchymal Stem Cells In Vitro And In Vivo", Grant KO 2119/8-1)

J. Jansen
A. Schaap-Oziemlak
 Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands

H.J. Looijenga
 Erasmus MC-University Medical Center (Daniel den Hoed Cancer Center), Rotterdam, The Netherlands

Ali Ghodsizad
 The Methodist Hospital, Houston, Texas, USA


Previous collaborations :
J.A. Airey
E.J. Coletti
 Department of Pharmacology, University of Nevada Medical School, Reno, Nevada, USA

A.I. Caplan
J. Gao
 Skeletal Research Center, Case Western Reserve University, Cleveland, Ohio, USA

G. Almeida-Porada
E. Zanjani
 Veterans Administration Medical Center, University of Nevada, Reno, Nevada, USA

A.M. Dickinson
X.-N. Wang
 Department of Haematology, Newcastle, UK
Organized/ Co-organized meetings
2. Workshop "Joint Master Program in Developmental and Stem Cell Biology"

Ruhr-University of Bochum - Heinrich-Heine-University of Düsseldorf – Fudan University in Shanghai
 Second workshop : October 4th - 7th, 2009


1. Workshop "Joint Master Program in Developmental and Stem Cell Biology"

Albert-Ludwigs-University of Freiburg - Heinrich-Heine-University of Düsseldorf – Fudan University in Shanghai
 First workshop : August 24th - 30th, 2008 (Program)

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Other
 
USSC-related publications:
Kögler G, Critser P, Trapp T, Yoder M (2009) Future of cord blood for non-oncology uses. Bone Marrow Transplant.

 Schaap-Oziemlak A, Raymakers RA, Bergevoet SM, Gilissen C, Jansen BJ, Adema GJ, Kögler G, le Sage C, Agami R, van der Reijden BA, Jansen J (2009) MicroRNA hsa-miR-135b regulates mineralization in osteogenic differentiation of human Unrestricted Somatic Stem Cells (USSCs). Stem Cells Dev.

Jansen BJ, Gilissen C, Roelofs H, Schaap-Oziemlak A, Veltman J, Raymakers RA, Jansen J, Kögler G, Figdor CG, Torensma R, Adema GJ
(2009) Functional Differences between mesenchymal stem cell populations are reflected by their transcriptome. Stem Cells Dev.

Langenbach F, Naujoks C, Kersten-Thiele PV, Berr K, Depprich R, Kübler N, Kögler G, Handschel J (2009) Osteogenic differentiation influence stem cell migration out of scaffold free microspheres. Tissue Eng Part A.

Buchheiser A, Liedtke S, Looijenga LH, Kögler G (2009) Cord blood for tissue regeneration. J Cell Biochem. 108(4):762-8.

van den Berk LC, Jansen BJ, Siebers-Vermeulen KG, Netea MG, Latuhihin T, Bergevoet S, Raymakers RA, Kögler G, Figdor CC, Adema GJ, Torensma R (2009) Toll-like receptor triggering in cord blood mesenchymal stem cells. J Cell Mol Med.

Willemze R, Rodrigues CA, Labopin M, Sanz G, Michel G, Socié G, Rio B, Sirvent A, Renaud M, Madero L, Mohty M, Ferra C, Garnier F, Loiseau P, Garcia J, Lecchi L, Kögler G, Beguin Y, Navarrete C, Devos T, Ionescu I, Boudjedir K, Herr AL, Gluckman E, Rocha V; Eurocord-Netcord and Acute Leukaemia Working Party of the EBMT (2009) KIR-ligand incompatibility in the graft-versus-host direction improves outcomes after umbilical cord blood transplantation for acute leukemia. Leukemia 23(3):492-500

Brand A, Rebulla P, Engelfriet CP, Reesink HW, Beguin Y, Baudoux E, Kögler G, Ebrahimi M, Grazzini G, Costa AN, Bosi A, Sacchi N, Lombardini L, Pupella S, Lecchi L, Garcidueñas ED, van Beckhoven JM, de Wit HJ, Fibbe WE, Zhiburt EB, Bart T, Beksaç M, Navarrete C, Regan F (2008) Cord blood banking. Vox Sang. 95(4):335-48

Trapp T, Kögler G, El-Khattouti A, Sorg RV, Besselmann M, Föcking M, Bührle CP, Trompeter I, Fischer JC, Wernet P (2008) Hepatocyte growth factor/c-MET axis-mediated tropism of cord blood-derived unrestricted somatic stem cells for neuronal injury. J Biol Chem. 21;283(47):32244-53

Winter M, Wang XN, Däubener W, Eyking A, Rae M, Dickinson AM, Wernet P, Kögler G, Sorg RV (2008) Suppression of Cellular Immunity by Cord Blood-Derived Unrestricted Somatic Stem Cells is Cytokine Dependent. J Cell Mol Med.

Liedtke S, Stephan M, Kögler G (2008) Oct 4 expression revisited: potential pitfalls for data misinterpretation in stem cell research. Journal Biol. Chemistry 389:845

Greschat S, Schira J, Kury P, Rosenbaum C, de Souza Silva MA, Kogler G, Wernet P, Muller HW (2008) Unrestricted Somatic Stem Cells from Human Umbilical Cord Blood Can be Differentiated into Neurons with a Dopaminergic Phenotype. Stem Cells Dev 17:221

Ghodsizad A, Niehaus M, Kogler G, Martin U, Wernet P, Bara C, Khaladj N, Makoui M, Thiele J, Mengel M, Karck M, Klein H, Gams E, Haverich A, Ruhparwar A (2008) Transplanted human cord blood derived USSC improve left-ventricular function and prevent left-ventricular dilation and scar formation after acute myocardial ischemia. Heart 95(1):27-35.

Radke TF, Buchheiser A, Lefort A, Maleki M, Wernet P, Kogler G (2007) GMP-conform generation and cultivation of USSC from cord blood using the SEPAX-separation method and a closed culture system applying cell stacks. Blood 110:367 (abstract)

Liedtke S, Enczmann J., Waclawczyk S, Wernet  P, Koegler G (2007) Oct4 and Its Pseudogenes Confuse Stem Cell Research. Cell Stem Cell 1:364

Sensken S, Waclawczyk S, Knaupp AS, Trapp T, Enczmann J, Wernet P, Kogler G (2007) In vitro differentiation of human cord blood-derived unrestricted somatic stem cells towards an endodermal pathway. Cytotherapy 9:362

Kogler G, Sensken S, Wernet P (2006) Comparative generation and characterization of pluripotent unrestricted somatic stem cells with mesenchymal stem cells from human cord blood. Exp Hematol 34:1589

Kogler G, Radke TF, Lefort A, Sensken S, Fischer J, Sorg RV, Wernet P (2005) Cytokine production and hematopoiesis supporting activity of cord blood-derived unrestricted somatic stem cells. Exp Hematol 33:573

Kogler G, Sensken S, Airey JA, Trapp T, Muschen 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, Muller HW, Zanjani E, Wernet P (2004) A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. J Exp Med 200:123
Awards:
2009 - Poster price Stem Cell Network North Rhine Westphalia:
Stefanie Geyh, Thomas Krenz, Simone Maria Kluth, Peter Wernet, Constanze Wiek, Helmut Hanenberg, Anja Buchheiser, Gesine Kögler
"Generation of clonal derived Unrestricted Somatic Stem Cells (USSC) from cord blood and analysis of their expression and differentiation potential"

2009 - ASH travel award
Amelie Pia Houben, Anja Buchheiser, Murat Aktas, Johannes Fischer, Peter Wernet, Gesine Koegler
"Age-Related Differences Between Unrestricted Somatic Stem Cells from Cord Blood and Bone Marrow Derived Mesenchymal Stroma Cells."


Important citations:
Science 315, 760 (2007)


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