Researchers from Tel Aviv University and the Leibniz Institute in Dresden have developed a 3D material with tunable structure, stiffness, and cytokine binding. In culture, it helped expand stem and hematopoietic progenitor cells, while maintaining their primary characteristics and the ability to form colonies.
Stem cells in the bone marrow produce red blood cells, white blood cells, and platelets throughout our lives. The ability to grow them outside the body may aid in research, transplantation, and the development of cell therapies, but it poses a fundamental difficulty: When the cells are removed from their natural environment and attempted to multiply them in culture, some may lose the properties that define them as stem cells and begin to differentiate.
A team from Tel Aviv University and the Leibniz Institute for Polymer Research in Dresden has developed a 3D hydrogel designed to mimic some of the mechanical and biochemical signals received by cells in the bone marrow. The hydrogel is made of peptides andGlycosaminoglycans, a family of polysaccharides also found in the extracellular matrix of the body. The researchers showed that a controlled change in the level of sulfation of a sulfatide-like component Heparin Allows you to program the properties of the material and create an environment that supports stem cells andstem cells Human hematopoiesis.
The study was led by Prof. Ayala Lampel from Tel Aviv University and Prof. Carsten Werner from the Leibniz Institute. The first author is Shirl Wertnik From the Shmonis School of Biomedical and Cancer Research at Tel Aviv University. The article was published in the journal Advanced Functional Materials on August 10, 2026.
Not just a bed, but a niche
A hydrogel is a water-rich polymer network. It can provide cells with a soft, three-dimensional substrate, but in the case of blood stem cells, this is not enough. In the bone marrow, the cells reside in a complex “niche”: a local environment that exerts mechanical forces on them, binds signaling proteins, and presents them to the cells at the appropriate time and concentration. This combination helps determine whether the cell will remain a stem cell, divide, or differentiate into a mature blood cell.
In the new system, the peptides form tiny fibers, while the sulfated glycosaminoglycans participate in the network organization and bind Cytokines—Signaling proteins that regulate cell behavior. Thus, the material not only serves as a skeleton. It also stores and presents signaling molecules to cells, similar to some of the functions of the extracellular matrix.
A chemical switch that adjusts the material
Sulfation is the addition of sulfate groups to a molecule. These groups carry a negative electrical charge, so their number and distribution affect the interactions between heparin and the charged peptides. The researchers combined peptides designed to bind heparin with heparin derivatives with three degrees of sulfation, and examined how the chemical changes translated into the structure and properties of the hydrogel.
It turned out that highly sulfated glycosaminoglycans can act as a facilitator for self-assembly. In some cases, the peptides promoted a transition from a random coil to a beta-sheet-rich structure, thus activating gel formation even without permanent covalent bonds. The reversible interactions create a viscoelastic network that can respond to and relax under load in a manner somewhat reminiscent of a natural extracellular matrix.
The experiments showed that the material's stiffness and its ability to bind cytokines can be tuned through molecular design. However, the two variables are not completely separate: changing the charge affects both assembly and protein binding. To find a suitable composition for blood cells, the researchers used a systematic design of experiments approach, exploring a range of chemical and mechanical combinations rather than changing a single factor at a time.
Goal: Preserve the primary cells
The optimal composition was rich in heparin and had a charge balance that supported the formation of a uniform network. When the researchers cultured human hematopoietic stem and progenitor cells in it, they were able to expand the cell population while maintaining markers associated with primary populations and clonogenic potential—the ability of a single cell to form a colony of blood cells under test conditions.
The comparison with conventional suspension culture is important for understanding the result. The hydrogel was not just designed to achieve the largest number of cells. According to the researchers, it shifted the balance from mass-scale culture toward preferential preservation of cells with primary characteristics and function. In stem cell culture, the quality and function of the population may be as important as the total quantity.
The researchers also identified the overall negative charge of the network as a key factor in the hydrogel's uniformity and cell support. This is a design principle that could help in the development of other materials: instead of relying solely on trial and error, it is possible to link peptide sequence, glycosaminoglycan chemistry, nanoscale structure, gel mechanics, and biological outcome.
No medical treatment yet
The findings present a promising platform for culture and research, but this is not yet a treatment tested in humans. Before clinical use, it will be necessary to show that the system works consistently with cells from different donors, that it can be produced under controlled medical conditions, and that the expanded cells are safe and functional after transplantation. Molecular markers and colony formation are important metrics, but are not a substitute for long-term functional testing in vivo.
The principle may also be useful beyond the circulatory system. Many cells depend on a local niche that connects mechanics, structure, and biochemical signaling. Therefore, programmed combinations of peptides and glycosaminoglycans may be used in the future to develop culture systems, deliver proteins, and engineer cellular environments in regenerative medicine. Each such application will require a separate adaptation to the cell type and desired function.
Questions and Answers
What are hematopoietic stem cells and progenitor cells?
These are cells that form the blood cell systems. Hematopoietic stem cells are capable of renewing themselves over time and giving rise to different lineages of blood cells. The stem cells are already in more advanced stages of differentiation, but can still divide and form several types of cells.
What is the role of the hydrogel in the research?
The hydrogel creates a 3D culture environment that mimics some of the characteristics of the bone marrow niche. It provides mechanical support and also binds cytokines, allowing us to examine how a combination of stiffness and biochemical signaling affects the cells.
Why is sulfation level important?
The sulfate groups give glycosaminoglycans a negative charge. Changing the level of sulfation affects the binding to peptides, the self-assembly of the network, and its ability to bind signaling proteins. It therefore serves as a kind of chemical tuning knob for the material's properties.
Is the hydrogel ready for use in bone marrow transplants?
No. The study was conducted in culture and presents design principles and preliminary results in human cells. Further studies, safety testing, and functional trials are needed before clinical use can be considered.
What is clonogenic potential?
This is a measure of the ability of a single cell to divide and form a colony of progeny cells under laboratory conditions. Maintaining this ability after growth in the hydrogel indicates that the cells not only survived, but retained an important function associated with stem and progenitor cells.
The scientific article
More on the subject on the science website
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- Researchers at Tel Aviv University have developed technology to identify cancer stem cells that cause leukemia.
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