Morphological, molecular and functional differences of adult bone marrow- and adipose-derived stem cells isolated from rats of different ages

• Published in: Experimental cell research Vol. 318; no. 16; pp. 2034 - 2048
• Main Authors: Mantovani, Cristina, Raimondo, Stefania, Haneef, Maryam S., Geuna, Stefano, Terenghi, Giorgio, Shawcross, Susan G., Wiberg, Mikael
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2012; Elsevier BV
• Subjects: 60 APPLIED LIFE SCIENCES; Adipocytes - cytology; Adipocytes - metabolism; Adipose Tissue - cytology; Adipose Tissue - metabolism; Adult Stem Cells - cytology; Adult Stem Cells - metabolism; Age; AGING; Animals; Animals, Newborn; Biomarkers - metabolism; BONE MARROW; Bone Marrow Cells - cytology; Bone Marrow Cells - metabolism; Cellular Senescence - genetics; Coculture Techniques; DRUGS; Gene Expression Regulation, Developmental; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; MITOCHONDRIA; NERVE CELLS; Neurites - physiology; Notch; p38; p53; POLYMERASE CHAIN REACTION; PROTEINS; RATS; Receptor, Notch2 - genetics; Receptor, Notch2 - metabolism; Rodents; Schwann Cells - cytology; Schwann Cells - metabolism; Senescence; STEM CELLS; Stro1; Strol; TRANSMISSION ELECTRON MICROSCOPY; Mitochondria; Senescence; p38; Notch; Aging; Stro1; p53
• ISSN: 0014-4827; 1090-2422; 1090-2422
• DOI: 10.1016/j.yexcr.2012.05.008

Adult mesenchymal stem cells have self-renewal and multiple differentiation potentials, and play important roles in regenerative medicine. However, their use may be limited by senescence or age of the donor, leading to changes in stem cell functionality. We investigated morphological, molecular and functional differences between bone marrow-derived (MSC) and adipose-derived (ASC) stem cells isolated from neonatal, young and old rats compared to Schwann cells from the same animals. Immunocytochemistry, RT-PCR, proliferation assays, western blotting and transmission electron microscopy were used to investigate expression of senescence markers. Undifferentiated and differentiated ASC and MSC from animals of different ages expressed Notch-2 at similar levels; protein-38 and protein-53 were present in all groups of cells with a trend towards increased levels in cells from older animals compared to those from neonatal and young rats. Following co-culture with adult neuronal cells, dMSC and dASC from animals of all ages elicited robust neurite outgrowth. Mitotracker® staining was consistent with ultrastructural changes seen in the mitochondria of cells from old rats, indicative of senescence. In conclusion, this study showed that although the cells from aged animals expressed markers of senescence, aged MSC and ASC differentiated into SC-like cells still retain potential to support axon regeneration. ► Aged MSC and ASC differentiated into Schwann-like cells support axon regeneration. ► p53 expression does not appreciably influence the biology of Schwann or stem cells. ► Notch 2 expression was similar in cells derived from animals of different ages. ► Proliferation rates of dMSC varied little over time or with animal age.