Aging as modulator and target of cell based therapies
Claire Fabian1, Yahaira Naaldijk1, Lusine Danielyan2, Alexandra Stolzing1+3
Regenerative medicine is investigating (stem) cell transplantations as a treatment for many diseases of the elderly. Cell therapies often show promising results in animal models, however the translation into large clinical trials are difficult. This might be in part because we do not know much about the mechanisms of action of the used cells, the optimal cell dose, the best delivery route but partly because we do not take the donor age of the cells into account and pre-clinical trials are mostly run in young animals only. I will discuss the role of aging in stem cell therapies but also show initial results on the use of cell therapy to delay brain aging.
I have shown that mesenchymal stem cells decrease functional activity if they are derived from older donors or have been expanded in vitro. One question is therefore if donor age has an impact on cell therapy outcomes. In addition the recipient age also has to be investigated as it changes the environment in which the cells are transplanted into.
Material & Methods: We transplanted mouse mesenchymal stem cells or microglia into mice (young, aged and Alzheimer). Cells were either from young or mature donors. Cells were tracked either using eGFP or the y-chromosome. Histology and real time PCR were performed to analyse the status of inflammation.
Results: We find that aged donor cells were not engrafting well, with this being more pronounced for microglia then for MSC. Interestingly more cells were found in aged/diseased brains compared to young brains and this was linked to the amount of chemo-attractant MCP-1 expression. Young cells minimise inflammation levels in the brain of AD mice and in aged mice, however this was not found for aged cells.
Conclusion: Donor age as well as recipient age modifies cell migration and engraftment and has to be taken into consideration when investigating cell therapies. Different cell types seem to be able to minimise inflammation in aged or diseases brains, also translating into improved animal behaviour.
Claire Fabian1, Yahaira Naaldijk1, Lusine Danielyan2, Alexandra Stolzing1+3
- Leipzig University, Germany
- Tubingen University, Germany
- Loughborough University, Centre for Biological Engineering, Wolfson School, UK
Regenerative medicine is investigating (stem) cell transplantations as a treatment for many diseases of the elderly. Cell therapies often show promising results in animal models, however the translation into large clinical trials are difficult. This might be in part because we do not know much about the mechanisms of action of the used cells, the optimal cell dose, the best delivery route but partly because we do not take the donor age of the cells into account and pre-clinical trials are mostly run in young animals only. I will discuss the role of aging in stem cell therapies but also show initial results on the use of cell therapy to delay brain aging.
I have shown that mesenchymal stem cells decrease functional activity if they are derived from older donors or have been expanded in vitro. One question is therefore if donor age has an impact on cell therapy outcomes. In addition the recipient age also has to be investigated as it changes the environment in which the cells are transplanted into.
Material & Methods: We transplanted mouse mesenchymal stem cells or microglia into mice (young, aged and Alzheimer). Cells were either from young or mature donors. Cells were tracked either using eGFP or the y-chromosome. Histology and real time PCR were performed to analyse the status of inflammation.
Results: We find that aged donor cells were not engrafting well, with this being more pronounced for microglia then for MSC. Interestingly more cells were found in aged/diseased brains compared to young brains and this was linked to the amount of chemo-attractant MCP-1 expression. Young cells minimise inflammation levels in the brain of AD mice and in aged mice, however this was not found for aged cells.
Conclusion: Donor age as well as recipient age modifies cell migration and engraftment and has to be taken into consideration when investigating cell therapies. Different cell types seem to be able to minimise inflammation in aged or diseases brains, also translating into improved animal behaviour.
