Leibniz Cooperative Excellence
Tick Tock: Linking Pathology and Lifestyle to Epigenetic Determinants of Biological vs. Chronological Stem Cell Aging
Aging leaves traces in our DNA. These traces, co-called DNA methylations, can be read by researchers to accurately determine an organism’s age. However, the determination of an organism’s age alone is not a proof that methylation itself directly affects the process of aging.
Causal relationships
This project aims to find exactly these causal connections between DNA methylation and aging. The researchers focus on hematopoietic stem cells, which give rise to immune cells. Immune cells are a particular example of cells that lose their functions in aging organisms. Therefore, the project will contribute significantly to our understanding of aging processes and to the development of therapeutic interventions.
Cooperating partners
Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
- (Coordinator)
German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE)
Hannover Medical School (MHH)
XpandHSC: Ex vivo Expansion of Functional Human Hematopoietic Stem Cells to Improve Therapy
One important limiting factor for successful clinical therapies using hematopoietic stem cells (HSCs) is the low number of histocompatible donor cells available for a specific patient. This caveat is based on the lack of understanding and, correspondingly, the lack of available protocols for the cultivation or even expansion of functional human HSCs in vitro.
Interdisciplinary approach
Our goal is to understand mechanisms of the regulation of HSCs and to use this understanding to expand human HSCs in vitro using advanced culture systems. In these culture systems we model the three-dimensional stem cell niche using molecular factors mediating the expansion of HSCs while preserving their functionality in vitro. Successful expansion of human HSCs is validated using innovative mouse models supporting human HSC engraftment in vivo.
Combined expertise
To meet this challenge we assembled a team that combines expertise in fundamental hematopoietic stem cell research (Waskow Lab), proteomics (Ori Lab) and clinical application (Heidel Lab) with expert bioinformatic analysis (Höfer Lab), and material scientists (Werner Lab). This collaboration involves the bioinformatic integration of gene expression and proteome data of HSCs and defined niche cells from their immediate microenvironment in vivo and will lead to the identification of novel regulatory candidate genes.
Development of improved therapies
The candidates will be used in innovative 3D culture systems based on tailored biohybrid hydrogels, a modular matrix platform based on glycosaminoglycans, and tested for their suitability for the cultivation of human HSCs. Validation of the most effective culture conditions that support the maintenance and expansion of human HSCs will be performed by transplantation experiments into excellent recipient mouse models generated within the consortium.
Taken together, our interdisciplinary approach will provide detailed information on the influence of extracellular matrix, cytokines, the mechanical properties of the cellular environment such as stiffness, and the effects of specific molecular regulators on the maintenance and expansion of HSCs in vitro, hopefully contributing to the development of improved clinical therapies.
Cooperating partners
Leibniz Institute on Aging – Fritz Lipmann Institute (FLI)
- (Coordinator)
Hannover Medical School (MHH)
Leibniz Institute of Polymer Research Dresden
German Cancer Research Center
Contact
Björn von Eyß
Coordinator
+49 3641 65-6047
bjoern.voneyss@~@leibniz-fli.de
Contact
Claudia Waskow
Coordinator
claudia.waskow@~@leibniz-fli.de
