Publications by Matthias Lütolf

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Clinical translation of human skeletal progenitor cells has been limited by the inability to reliably predict their regenerative performance, as current characterization methods rely on phenotypic markers or instructive differentiation assays that obscure intrinsic cell function. Here we demonstrate that human skeletal progenitor competence can only be revealed within a precisely defined and growth factor-free synthetic microenvironment. By independently tuning matrix mechanics, degradability, adhesion, and

Intestinal organoids are useful in vitro models for basic and translational studies aimed at understanding and treating disease. However, their routine culture relies on animal-derived matrices that limit translation to clinical applications. In fact, ther ...

Urine is a dynamic and highly variable biofluid. Urine-urothelium interactions are a critical yet underexplored factor in bladder homeostasis and urinary tract infections (UTIs). Here, we report on a human ‘mini-bladder’ model that exposes a stratified urothelium to urine of defined composition, and incorporates micturition. Prolonged exposure to high-solute concentration urine weakens tight junctions, dysregulates immune responses, and reduces bladder tissue resilience. This increases susceptibility to col

Urine is a dynamic and highly variable biofluid. Urine-urothelium interactions are a critical yet underexplored factor in bladder homoeostasis and urinary tract infections (UTIs). Here, we report on a human ‘mini-bladder’ model that exposes a stratified urothelium to urine of defined composition, and incorporates micturition. Prolonged exposure to high-solute concentration urine weakens tight junctions, dysregulates immune responses, and reduces bladder tissue resilience. This increases susceptibility to co

Cells in our tissues are exposed to complex arrays of biochemical and biophysical cues from their protein- and sugar-rich extracellular matrix (ECM). In concert with cell- intrinsic regulatory cascades, these temporally and spatially coordinated signals instruct cells to acquire specific fates, controlling, for example, cell division, differentiation, migration or apoptosis. Conversely, cells are constantly secreting signals that can trigger structural and biochemical microenvironmental changes, as is most

Multiple molecular and physical cues engage in complex interplay to afford the fine control over stem cell behavior that is required during tissue development, homeostasis, and repair. As a result of a close collaboration between biologists, engineers, and ...

Human mammary epithelial cells can proliferate and reorganize into polarized multi-cellular constructs in-vitro, thereby functioning as an important model system in recapitulating key steps of in-vivo morphogenesis. Current approaches to constructing such ...

c-MAF, highly expressed in villus small intestinal enterocytes, coordinates transcriptional programs for nutrient absorption. Enterocyte-specific c-MAF inactivation impairs dietary lipid handling but also leads to tuft cell expansion and adaptive gut lengt ...

The human genome harbors more than 4.5 million transposable element (TE)-derived insertions, the result of recurrent waves of invasion and internal propagation. Here they show that TEs belonging to evolutionarily recent subfamilies go on to regulate later ...

The perivascular niche is a complex microenvironment containing mesenchymal stem cells (MSCs), among other perivascular cells, as well as temporally organized biochemical and biophysical gradients. Due to a lack of conclusive phenotypic markers, MSCs' iden ...

The complex cellular microenvironment plays an important role in determining cell fate. For example, stem cells located in a microenvironment termed niche integrate a wide variety of extrinsic cues to take distinct fate choices. Capturing this multiple-inp ...

Embryo implantation into the uterus marks a key transition in mammalian development. In mice, implantation is mediated by the trophoblast and is accompanied by a morphological transition from the blastocyst to the egg cylinder. However, the roles of tropho ...

We sought to develop bioactive hydrogels to facilitate arterial healing, e.g., after balloon angioplasty. Toward this end, we developed a new class of proteolytically sensitive, biol. active polyethylene glycol (PEG)-peptide hydrogels that can be formed in situ to temporarily protect the arterial injury from blood contact. Furthermore, we incorporated endothelial cell-specific biol. signals with the goal of enhancing arterial reendothelialization. Here we demonstrated efficient endothelial cell anchorage an

Hematopoietic stem cells (HSCs) are responsible for life-long production of all mature blood cells. Under homeostasis, HSCs in their native bone marrow niches are believed to undergo asymmetric cell divisions (ACDs), with one daughter cell maintaining HSC ...

Human brain development begins with the formation of the neural tube, a neuroepithelium organized around a single continuous lumen that is patterned to specify distinct brain regions. Human pluripotent stem cell (hPSC)-derived neural organoids offer powerful models to study this process and its disruption in disease. However, most existing protocols rely on stochastic self-organization of hPSC aggregates, leading to high variability in tissue architecture and cell type composition, which limits reproducibil

Fate decisions in the embryo are controlled by a plethora of microenvironmental interactions in a three-dimensional niche. To investigate whether aspects of this microenvironmental complexity can be engineered to direct myogenic human-induced pluripotent s ...

The ability of the biomimetic peptides YIGSR, PHSRN and RGD to selectively affect adhesion and migration of human microvascular endothelial cells (MVEC) and vascular smooth muscle cells (HVSMC) was evaluated. Cell mobility was quantified by time-lapse vide ...

An enzymatically cross-linked polyethylene glycol (PEG)-based hydrogel was engineered to promote and align nerve cells in a three-dimensional manner. To render the injectable, otherwise bioinert, PEG-based material supportive for cell growth, its mechanica ...

The contribution of chemotherapy-induced tissue injury to individual susceptibility to metastasis remains largely unexplored. We report that chemotherapy indirectly prevents colorectal cancer (CRC) liver metastases by inducing a lasting systemic “chemomemory”. Chemotherapy-induced intestinal mucositis alters nutrient availability, promoting the expansion of tryptophan-metabolizing bacteria and production of the microbial metabolite indole-3-propionic acid (IPA). IPA reprograms bone marrow myelopoiesis by re

The difficulty of studying post-implantation development in mammals has sparked a flurry of activity to develop in vitro models, termed embryoids, based on self-organizing pluripotent stem cells. Previous approaches to derive embryoids either lack the phys ...

Matthias Lütolf

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Growth factor-free synthetic matrices reveal intrinsic skeletal progenitor competence

The Effect of Thiol Structure on Allyl Sulfide Photodegradable Hydrogels and their Application as a Degradable Scaffold for Organoid Passaging

A bioengineered human urothelial organoid model reveals the urine-urothelium interplay in tissue resilience and UPEC recurrence in urinary tract infections

A microphysiological human mini-bladder reveals urine-urothelium interplay in tissue resilience and UPEC recurrence in urinary tract infections

Synthetic biomaterials as cell-responsive artificial extracellular matrices

Biomaterials Approaches in Stem Cell Mechanobiology

Mammary epithelial morphogenesis in 3D combinatorial microenvironments

c-MAF coordinates enterocyte zonation and nutrient uptake transcriptional programs

Primate-specific transposable elements shape transcriptional networks during human development

Locally controlling mesenchymal stem cell morphogenesis by 3D PDGF-BB gradients towards the establishment of an in vitro perivascular niche

Artificial niche microarrays for identifying extrinsic cell-fate determinants

Embryo-uterine interaction coordinates mouse embryogenesis during implantation

MMP-2 sensitive, VEGF-bearing bioactive hydrogels for promotion of vascular healing

In Vivo Pre-Instructed HSCs Robustly Execute Asymmetric Cell Divisions In Vitro

Unified Generation of Regionalized Neural Organoids from Single-Lumen Neuroepithelium

An engineered multicellular stem cell niche for the 3D derivation of human myogenic progenitors from iPSCs

The selective modulation of endothelial cell mobility on RGD peptide containing surfaces by YIGSR peptides

Synthetic 3D PEG-Anisogel Tailored with Fibronectin Fragments Induce Aligned Nerve Extension

Chemotherapy-driven intestinal dysbiosis and indole-3-propionic acid rewire myelopoiesis to promote a metastasis-refractory state

Bioengineered embryoids mimic post-implantation development in vitro