Publications de Matthias Lütolf

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The recent demonstration that primary cells from the liver can be expanded in vitro as organoids holds enormous promise for regenerative medicine and disease modelling. The use of three-dimensional (3D) cultures based on ill-defined and potentially immunog ...

Brain organoids enable the mechanistic study of human brain development and provide opportunities to explore self-organization in unconstrained developmental systems1, 2–3. Here we establish long-term, live light-sheet microscopy on unguided brain organoid ...

The rapid increase in the number of approved therapeutic proteins, including recombinant antibodies, for diseases necessitating chronic treatments raises the question of the overall costs imposed on healthcare systems. It is therefore important to investig ...

Stem-cell-derived epithelial organoids are routinely used for the biological and biomedical modelling of tissues. However, the complexity, lack of standardization and quality control of stem cell culture in solid extracellular matrices hampers the routine ...

Epithelial organoids are most efficiently grown from mouse-tumour-derived, reconstituted extracellular matrix hydrogels, whose poorly defined composition, batch-to-batch variability and immunogenicity limit clinical applications. Efforts to replace such il ...

Most hematopoietic stem cells (HSC) in the bone marrow reside in a quiescent state and occasionally enter the cell cycle upon cytokine-induced activation. Although the mechanisms regulating HSC quiescence and activation remain poorly defined, recent studies have revealed a role of lipid raft clustering (LRC) in HSC activation. Here, we tested the hypothesis that changes in lipid raft distribution could serve as an indicator of the quiescent and activated state of HSCs in response to putative niche signals.

The laboratory culture of human stem cells seeks to capture a cellular state as an in vitro surrogate of a biological system. For the results and outputs from this research to be accurate, meaning-ful, and durable, standards that ensure reproducibility and ...

Specialized signaling centers orchestrate robust development and regeneration. Limb morphogenesis, for instance, requires interactions between the mesoderm and the signaling center apical-ectodermal ridge (AER), whose properties and role in cell fate decisions have remained challenging to dissect. To tackle this, we developed mouse embryonic stem cell (mESC)–based heterogeneous cultures and a three-dimensional (3D) organoid model, termed budoids, comprising cells with AER, surface ectoderm, and mesoderm pro

Organoids for modelling the physiology and pathology of gastrointestinal tissues are constrained by a poorly accessible lumen. Here we report the development and applicability of bilaterally accessible organoid-derived patterned epithelial monolayers that ...

During wound healing, the distribution, availability, and signaling of growth factors (GFs) are orchestrated by their binding to extracellular matrix components in the wound microenvironment. Extracellular matrix proteins have been shown to modulate angiog ...

Inducing organogenesis in 3D culture is an important aspect of stem cell research. Anterior neural structures have been produced from large embryonic stem cell (ESC) aggregates, but the steps involved in patterning such complex structures have been ill def ...

Blood stem cells, also termed hematopoietic stem cells (HSC), are used clinically to treat numerous blood cancers. However, due to the low numbers of HSCs that can be isolated from the bone marrow of donors, broad application of this treatment is severely hindered. A robust method is needed that enables in vitro propagation and expansion of HSCs. In addition, as soon as HSCs are removed from their bone marrow niches and put in culture, they begin to differentiate and lose their multipotency. Therefore, a di

Hematopoietic stem cells (HSCs) are capable of extensive self-renewal in vivo and are successfully employed clinically to treat hematopoietic malignancies, yet are in limited supply as in culture this self-renewal capacity is lost. Using an approach at the ...

Cell extrusion is essential for homeostatic self-renewal of the intestinal epithelium. Extrusion is thought to be triggered by crowding-induced compression of cells at the intestinal villus tip. In this study, we found instead that a local “tug-of-war” competition between contractile cells regulated extrusion in the intestinal epithelium. We combined quantitative live microscopy, optogenetic induction of tissue tension, genetic perturbation of myosin II activity, and local disruption of the basal cortex in

Organoids are powerful models for studying tissue development, physiology, and disease. However, current culture systems disrupt the inductive tissue-tissue interactions needed for the complex morphogenetic processes of native organogenesis. Here, we show ...

In the context of a cellular therapy for diabetes, methods for pancreatic progenitor expansion and subsequent differentiation into insulin-producing beta cells would be extremely valuable. Here we establish three-dimensional culture conditions in Matrigel ...

Pluripotent stem cells hold great promise for many pharmaceutical and therapeutic applications. However, the lack of scalable methodologies to expand these cells to clinically relevant numbers is a major roadblock in realizing their full potential. To addr ...

Extracellular mimetic hydrogels formed from peptide crosslinkers and polyethylene glycol monomers permit cell-controlled invasion. The use of matrix metalloproteinase specific peptides might further allow for selective control of different cell-type invasi ...

A quant. structure-reactivity relationship for the Michael-type addn. of thiols onto acrylates was detd. Several thiol-contg. peptides were investigated by examg. the correlation between the second-order rate const. of their addn. onto PEG-diacrylate and the pKa of the thiols within a peptide. By introducing charged amino acids in close proximity to a cysteine, the pKa of the thiol was systematically modulated by electrostatic interactions. Pos. charges from the amino acid arginine decreased the pKa of the

High-content assays have the potential to drastically increase throughput in cell biology and drug discovery, but handling and culturing large libraries of cells such as primary tumor or cancer cell lines requires expensive, dedicated robotic equipment. We ...

Matthias Lütolf

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Mechano-modulatory synthetic niches for liver organoid derivation

Morphodynamics of human early brain organoid development

A high-capacity cell macroencapsulation system supporting the long-term survival of genetically engineered allogeneic cells

High-throughput automated organoid culture via stem-cell aggregation in microcavity arrays

Synthetic dynamic hydrogels promote degradation-independent in vitro organogenesis

Identification of in vitro HSC fate regulators by differential lipid raft clustering

ISSCR standards for the use of human stem cells in basic research

Specialized signaling centers direct cell fate and spatial organization in a mesodermal organoid model

Patterned gastrointestinal monolayers with bilateral access as observable models of parasite gut infection

The heparin binding domain of von Willebrand factor binds to growth factors and promotes angiogenesis in wound healing

3D Reconstitution of the Patterned Neural Tube from Embryonic Stem Cells

Control of Adult Stem Cell Function in Bioengineered in vitro Niches

Perturbation of single hematopoietic stem cell fates in artificial niches

Epithelial tension controls intestinal cell extrusion

Capturing Cardiogenesis in Gastruloids

Artificial three-dimensional niches deconstruct pancreas development in vitro

Development of bioactive hydrogel capsules for the 3D expansion of pluripotent stem cells in bioreactors

Cell specific ingrowth hydrogels

Systematic Modulation of Michael-Type Reactivity of Thiols through the Use of Charged Amino Acids

Live mammalian cell arrays