Human somatic cells in regenerative medicine : In vitro characterization of mesenchymal stem cells and chondrocytes
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AbstractTissue engineering is a new treatment strategy available to patients with injuries and diseases. The goal is to rebuild or replace damaged or dead tissue. The means is stem cells or differentiated organ specific cells, with or without scaffolds to ensure that the new tissue acquires the right shape. The present thesis is based on research performed within cell/stem cell biology, with the aim to improve treatment modalities in regenerative medicine.
In order to ensure the best results from tissue engineering treatment strategies, the cells used need to be characterized in detail, and in vitro cell expansion protocols need to be optimalized. In his thesis, cand. scient Aboulghassem Shahdadfar has studied three cell populations with considerable potential in protocols in regenerative medicine. He identified mesenchymal stem cells (MSC) in adipose tissue, and defined their phenotype and gene expression. He showed that these cells could differentiate to several different lineages, and characterized the changes in gene expression induced in these cells by in vitro cell culture. Another population of MSC is found in the bone marrow. Using these cells, Shahdadfar showed that serum from the bone marrow donor could be used for in vitro cell expansion in stead of fetal calf serum, thus avoiding the risk of transfer of zoonoses and immune-stimulating xenogeneic proteins. The cells thus obtained seemed also to be more genetically stable.
Chondrocytes obtained from biopsies of articular cartilage has for some time been used for treatment of focal lesions of the hyaline cartilage of the knee. However, in the course of in vitro culture these cells lose the ability to produce the right constituents of hyaline extracellular matrix. Shahdadfar in this thesis presents an improved cell culture method for chondrocytes, which ensures that the cells maintain the ability to produce the right extracellular matrix. Cells cultured in this way are already being used in patients.
LIST OF PAPERS. This thesis is based on the following papers:
Shahdadfar A*, Boquest AC*, Frønsdal K, Sigurjonsson O, Tunheim SH, Collas P, and Brinchmann JE. Isolation and transcription profiling of purified uncultured human stromal stem cells: alteration of gene expression after in vitro cell culture. Mol Biol Cell. 2005 Mar;16(3):1131-41 Abstract. * These authors contributed equally to this work.
Shahdadfar A, Frønsdal K, Haug T, Reinholt FP, and Brinchmann JE. In vitro expansion of human mesenchymal stem cells: choice of serum is a determinant of cell proliferation, differentiation, gene expression, and transcriptome stability. Stem Cells. 2005. 23(9):1357-66 Abstract.
Shahdadfar A, Løken S, Tunheim SH, Dahl JA, Collas P, Reinholt FP, Engebretsen L, and Brinchmann JE. Persistence of collagen type II synthesis and secretion in rapidly proliferating human articular chondrocytes in vitro. Submitted manuscript