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Original Article |
1 Institute of Immunology, Rikshospitalet University Hospital, Oslo, Norway
2 Centre for Occupational and Environmental Medicine, Rikshospitalet University Hospital, Oslo, Norway
3 Institute and Department of Pathology, University of Oslo and Rikshospitalet University Hospital, Oslo, Norway
* To whom correspondence should be addressed. E-mail: j.e.brinchmann{at}medisin.uio.no.
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Abstract |
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Human marrow mesenchymal stem cells (hMSC) represent an appealing source of adult stem cells for cell therapy and tissue engineering as they are easily obtained and expanded while maintaining their multilineage differentiation potential. All current protocols for in vitro culture of hMSC include fetal bovine serum (FBS) as nutritional supplement. FBS is an undesirable additive to cells that are expanded for therapeutic purposes in humans, since the use of FBS carries the risk of transmitting viral and prion diseases and proteins that may initiate xenogeneic immune responses. In the present study, we have therefore investigated if autologous serum (AS) or allogeneic human serum (alloHS) could replace FBS for the expansion of hMSC in vitro. We discovered that the choice of serum affected hMSC at several different levels. First, hMSC in AS proliferated markedly faster than hMSC in FBS, while use of alloHS resulted in hMSC growth arrest and death. Second, hMSC in FBS differentiated more rapidly towards mesenchymal lineages compared with hMSC in AS. Interestingly, genome-wide microarray analysis identified a number of transcripts involved in cell cycle and differentiation which were differentially regulated between hMSC in FBS and AS. Finally, a number of transcripts, including some involved in cell cycle inhibition, were up-regulated in hMSCs in FBS at a late passage, while the hMSC transcriptome in AS was remarkably stable. Thus, hMSC may be expanded rapidly and with stable gene expression in AS in the absence of growth factors, whereas FBS induces a more differentiated and less stable transcriptional profile.
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