Biology subjects

Woersdoerfer, P.

Publications and source records attributed to Woersdoerfer, P..

4 recordsLinked to original sources

bioRxiv2026

Generation of Self-Organizing Macrovascular Constructs by Bioprinting human iPSC-Derived Mesodermal Progenitor Cells

Vascularization remains a major obstacle in tissue engineering. Here, we introduce a developmentally inspired bioprinting strategy to generate centimeter-scale, self-organising "mother vessel" constructs from iPSC-derived human mesodermal progenitor cells (hiMPCs). By systematically optimizing the bioink composition, we identified a formulation that combines high print fidelity, mechanical stability and cell compatibility within a single-step bioprinting process. Within the first week after printing, hiMPCs in the "mother vessel" constructs underwent spontaneous differentiation and morphogenesis, forming intima-, media-, and adventitia-like layers containing CD31 endothelial, SMA mural and CD34/CD150 progenitor cells. Remarkably, Iba1 macrophage-like cells appeared despite their absence in the initial population, indicating intrinsic differentiation into both vascular and non-vascular lineages essential for angiogenesis, remodeling and tissue homeostasis. Surrounding the newly formed vessel wall-like structure was a broad, vascularized mesodermal tissue compartment that also contained the above-mentioned progenitors. Co-culture with prevascularized mesodermal organoids resulted in early structural interconnection of microvessels with the printed wall, representing a prerequisite for subsequent hierarchical vascular network formation. As a proof-of-concept, the mother vessel withstood controlled flow conditions in a bioreactor without detectable leakage, demonstrating its principal suitability for perfusion analyses. Together, these findings establish a biologically driven platform that bridges macro- and microvascularization. This may pave the way toward perfusable, vascularized larger tissue constructs, a major bottleneck in regenerative biofabrication.

bioengineering↗

bioRxiv2025

Tissue resident macrophages innately develop in a human iPSC-derived cardiac organoid model

The heart is the first functional organ to develop during embryogenesis, forming in parallel with the vasculature and hematopoietic cell lineages. To advance our understanding of human cardiac development and disease, human induced pluripotent stem cell-derived cardiomyocytes offer a promising in vitro model. However, conventional 2D culture systems lack the complexity required to recapitulate the intricate interactions of different cell types leading to fully functional and mature cardiac tissue. Here, we present a cardiac organoid model that mimics several aspects of cardiogenesis. The organoids develop a functional myocardium consisting of cardiomyocytes and fibroblasts capable of spontaneous rhythmic contractions. The myocard is interspersed with a branched endothelial network. Additionally, macrophages develop within the organoids and integrate into the myocardium. In summary, we describe a complex 3D cell culture platform to study human heart tissue development with all the involved cell types (cardiomyocytes, fibroblasts, endothelial cells, macrophages), paving the way for new insights into the role of macrophages in cardiac development and disease.

developmental biology↗

bioRxiv2022

Human neuro-mesodermal assembloids recapitulate aspects of peripheral nervous system development in vitro

Here we describe a novel neuro-mesodermal assembloid model which recapitulates aspects of peripheral nervous system (PNS) development such as neural crest cell (NCC) induction, delamination, migration and sensory as well as sympathetic ganglion formation. The ganglia send neuronal projections to the mesodermal as well as the neural compartment. Axons in the mesodermal part are associated with Schwann cells. In addition, peripheral ganglia as well as nerve fibers interact with the co-developing vascular plexus, forming a neurovascular niche. Finally, developing sensory ganglia show response to capsaicin treatment indicating their functionality. The presented assembloid model could help to uncover mechanisms of NCC delamination, migration and PNS development in the human tissue context. Moreover, the model could be used for toxicity screenings or drug testing. The co-development of mesodermal and neuroectodermal tissues and of a well-organized vascular plexus along with a peripheral nervous system allows to investigate the crosstalk between neuroectoderm and mesoderm and between peripheral neurons/neuroblasts and endothelial cells. Such interactions influence NCC delamination and migration, sensory neuron differentiation and rearrangement of the primitive vascular plexus in the embryo.

developmental biology↗

bioRxiv2021

Human iPSC-derived mesodermal progenitor cells preserve their vasculogenesis potential after extrusion and form hierarchically organized blood vessels

Post-fabrication formation of a proper vasculature remains an unresolved challenge in bioprinting. Established strategies focus on the supply of the fabricated structure with nutrients and oxygen and either rely on the mere formation of a channel system using fugitive inks, or additionally use mature endothelial cells and/or peri-endothelial cells such as smooth muscle cells for the formation of blood vessels in vitro. Functional vessels, however, exhibit a hierarchical organization and multilayered wall structure that is important for their function. Human induced pluripotent stem cell-derived mesodermal progenitor cells (hiMPCs) have been shown to possess the capacity to form blood vessels in vitro, but have so far not been assessed for their applicability in bioprinting processes. Here, we demonstrate that hiMPCs, after formulation into an alginate / collagen type 1 bioink and subsequent extrusion, retain their ability to give rise to the formation of complex vessels that display a hierarchical network in a process that mimicks the embryonic steps of vessel formation by vasculogenesis. Histological evaluations at different time points of extrusion revealed initial formation of spheres, followed by lumen formation and further structural maturation as evidenced by building a multilayered vessel wall and a vascular network. These findings are supported by immunostainings for endothelial and peri-endothelial cell markers as well as electron microscopic analyses at the ultrastructural level. Moreover, capillary-like vessel structures deposited a basement membrane-like matrix structure at the basal side between the vessel wall and the alginate-collagen matrix. These results evidence the applicability and great potential of hiMPCs for the bioprinting of vascular structures mimicking the basic morphogenetic steps of de novo vessel formation during embryogenesis.

bioengineering↗