Address of Corresponding Author

Cells Tissues Organs 2005;179:91-101 (DOI: 10.1159/000085000)

  Key Words

• Adult stem cells
• Mesenchymal tissue
• Microenvironment
• Tissue aggregates

  Abstract

Adult mesenchymal stem cells with multilineage differentiation potentially exist in the bone marrow, but have also been isolated from the peripheral blood. The differentiation of stem cells after leaving their niches depends predominately on the local milieu and its new microenvironment, and is facilitated by soluble factors but also by the close cell-cell interaction in a three-dimensional tissue or organ system. We have isolated CD34-negative, mesenchymal stem cell lines from human bone marrow and peripheral blood and generated monoclonal cell populations after immortalization with the SV40 large T-antigen. The cultivation of those adult stem cell clones in an especially designed in vitro environment, including self-constructed glass capillaries with defined growth conditions, leads to the spontaneous establishment of pleomorphic three-dimensional cell aggregates (spheroids) from the monoclonal cell population, which consist of cells with an osteoblast phenotype and areas of mineralization along with well-vascularized tissue areas. Modifications of the culture conditions favored areas of bone-like calcifications. After the transplantation of the at least partly mineralized human spheroids into different murine soft tissue sites but also a dorsal skinfold chamber, no further bone formation could be observed, but angiogenesis and neovessel formation prevailed instead, enabling the transplanted cells and cell aggregates to survive. This study provides evidence that even monoclonal adult human CD34-negative stem cells from the bone marrow as well as peripheral blood can potentially differentiate into different mesenchymal tissues depending on the local milieu and responding to the needs within the microenvironment.

Copyright © 2005 S. Karger AG, Basel

  Author Contacts

Ralf Huss, MD
Institute of Pathology, University of Munich, Thalkirchner Strasse 36
DE-80337 Munich (Germany)
Tel. +49 89 5160 4953, Fax +49 89 5160 4043
E-Mail Ralf.Huss@patho.med.uni-muenchen.de

  Article Information

S.M. and J.H. contributed equally to this work.

Accepted after revision: December 21, 2004
Number of Print Pages : 11
Number of Figures : 6, Number of Tables : 0, Number of References : 43