title: A mesenchymal stromal cell gene signature for donor age.
abstract: Human aging is associated with loss of function and regenerative capacity. Human bone marrow derived mesenchymal stromal cells (hMSCs) are involved in tissue regeneration, evidenced by their capacity to differentiate into several lineages and therefore are considered the golden standard for cell-based regeneration therapy. Tissue maintenance and regeneration is dependent on stem cells and declines with age and aging is thought to influence therapeutic efficacy, therefore, more insight in the process of aging of hMSCs is of high interest. We, therefore, hypothesized that hMSCs might reflect signs of aging. In order to find markers for donor age, early passage hMSCs were isolated from bone marrow of 61 donors, with ages varying from 17-84, and clinical parameters, in vitro characteristics and microarray analysis were assessed. Although clinical parameters and in vitro performance did not yield reliable markers for aging since large donor variations were present, genome-wide microarray analysis resulted in a considerable list of genes correlating with human age. By comparing the transcriptional profile of aging in human with the one from rat, we discovered follistatin as a common marker for aging in both species. The gene signature presented here could be a useful tool for drug testing to rejuvenate hMSCs or for the selection of more potent, hMSCs for cell-based therapy.
authors.affiliation: Department of Tissue Regeneration, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
authors.forename: Hugo
authors.initials: H
authors.lastname: Alves
authors.forename: Jetty
authors.initials: J
authors.lastname: van Ginkel
authors.forename: Nathalie
authors.initials: N
authors.lastname: Groen
authors.forename: Marc
authors.initials: M
authors.lastname: Hulsman
authors.forename: Anouk
authors.initials: A
authors.lastname: Mentink
authors.forename: Marcel
authors.initials: M
authors.lastname: Reinders
authors.forename: Clemens
authors.initials: C
authors.lastname: van Blitterswijk
authors.forename: Jan
authors.initials: J
authors.lastname: de Boer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D000818:Animals; D016922:Cellular Senescence / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005819:Genetic Markers / Q000235:genetics; D023281:Genomics; D006801:Humans; D019520:Living Donors; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008875:Middle Aged; D051381:Rats
chemical_list: D005819:Genetic Markers