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Age-dependent neuroectodermal differentiation capacity of human mesenchymal stromal cells: limitations for autologous cell replacement strategies.
Cytotherapy 2010; 12(1):17-30C

Abstract

BACKGROUND AIMS

Human adult bone marrow (BM)-derived mesenchymal stromal cells (hMSC) are reported to break germ layer commitment and differentiate into cells expressing neuroectodermal properties. Although it is of pivotal interest for cell replacement therapies for neurologic disorders, no data exist on the influence of the donor's age on this multipotent differentiation behavior.

METHODS

We evaluated various epigenetic neuroectodermal conversion protocols in adult hMSC derived from older donors (>45 versus 18-35 years of age) using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and immunocytochemistry. The protocols included single- and multi-step conversion-differentiation protocols combined with co-culture techniques. Furthermore, the age dependency of mesodermal differentiation potential and cell senescence were investigated.

RESULTS

The neuroectodermal differentiation potential of hMSC derived from old donors was completely lost, with no cells showing mature neuroectodermal phenotypes using single- and multi-step conversion-differentiation protocols and no improvement of neurogenesis by various co-culture conditions. Comparison of young versus old donor-derived hMSC showed fewer cells expressing early neuroectodermal marker proteins in the latter samples. qRT-PCR showed reduced expression of the proliferation marker KI67 and the neuroectodermal gene NES (nestin) in old donor-derived cells compared with young donor hMSC. Telomere length analysis showed no general cell aging.

CONCLUSIONS

Our data provide evidence that only young donor-derived hMSC can be epigenetically differentiated in vitro into neuroectodermal cells, pointing towards senescence of multipotentiality of old donor-derived hMSC. There is thus an urgent need to develop better protocols for successful neuroectodermal differentiation of hMSC from old individuals as a prerequisite for autologous cell replacement strategies for neurologic diseases in elderly patients.

Authors+Show Affiliations

Department of Neurology, Dresden University of Technology, Dresden, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19878082

Citation

Hermann, Andreas, et al. "Age-dependent Neuroectodermal Differentiation Capacity of Human Mesenchymal Stromal Cells: Limitations for Autologous Cell Replacement Strategies." Cytotherapy, vol. 12, no. 1, 2010, pp. 17-30.
Hermann A, List C, Habisch HJ, et al. Age-dependent neuroectodermal differentiation capacity of human mesenchymal stromal cells: limitations for autologous cell replacement strategies. Cytotherapy. 2010;12(1):17-30.
Hermann, A., List, C., Habisch, H. J., Vukicevic, V., Ehrhart-Bornstein, M., Brenner, R., ... Storch, A. (2010). Age-dependent neuroectodermal differentiation capacity of human mesenchymal stromal cells: limitations for autologous cell replacement strategies. Cytotherapy, 12(1), pp. 17-30. doi:10.3109/14653240903313941.
Hermann A, et al. Age-dependent Neuroectodermal Differentiation Capacity of Human Mesenchymal Stromal Cells: Limitations for Autologous Cell Replacement Strategies. Cytotherapy. 2010;12(1):17-30. PubMed PMID: 19878082.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Age-dependent neuroectodermal differentiation capacity of human mesenchymal stromal cells: limitations for autologous cell replacement strategies. AU - Hermann,Andreas, AU - List,Catrin, AU - Habisch,Hans-Jörg, AU - Vukicevic,Vladimir, AU - Ehrhart-Bornstein,Monika, AU - Brenner,Rolf, AU - Bernstein,Peter, AU - Fickert,Stefan, AU - Storch,Alexander, PY - 2009/11/3/entrez PY - 2009/11/3/pubmed PY - 2010/4/7/medline SP - 17 EP - 30 JF - Cytotherapy JO - Cytotherapy VL - 12 IS - 1 N2 - BACKGROUND AIMS: Human adult bone marrow (BM)-derived mesenchymal stromal cells (hMSC) are reported to break germ layer commitment and differentiate into cells expressing neuroectodermal properties. Although it is of pivotal interest for cell replacement therapies for neurologic disorders, no data exist on the influence of the donor's age on this multipotent differentiation behavior. METHODS: We evaluated various epigenetic neuroectodermal conversion protocols in adult hMSC derived from older donors (>45 versus 18-35 years of age) using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and immunocytochemistry. The protocols included single- and multi-step conversion-differentiation protocols combined with co-culture techniques. Furthermore, the age dependency of mesodermal differentiation potential and cell senescence were investigated. RESULTS: The neuroectodermal differentiation potential of hMSC derived from old donors was completely lost, with no cells showing mature neuroectodermal phenotypes using single- and multi-step conversion-differentiation protocols and no improvement of neurogenesis by various co-culture conditions. Comparison of young versus old donor-derived hMSC showed fewer cells expressing early neuroectodermal marker proteins in the latter samples. qRT-PCR showed reduced expression of the proliferation marker KI67 and the neuroectodermal gene NES (nestin) in old donor-derived cells compared with young donor hMSC. Telomere length analysis showed no general cell aging. CONCLUSIONS: Our data provide evidence that only young donor-derived hMSC can be epigenetically differentiated in vitro into neuroectodermal cells, pointing towards senescence of multipotentiality of old donor-derived hMSC. There is thus an urgent need to develop better protocols for successful neuroectodermal differentiation of hMSC from old individuals as a prerequisite for autologous cell replacement strategies for neurologic diseases in elderly patients. SN - 1477-2566 UR - https://www.unboundmedicine.com/medline/citation/19878082/Age_dependent_neuroectodermal_differentiation_capacity_of_human_mesenchymal_stromal_cells:_limitations_for_autologous_cell_replacement_strategies_ L2 - https://linkinghub.elsevier.com/retrieve/pii/10.3109/14653240903313941 DB - PRIME DP - Unbound Medicine ER -