Vascular organoids in cardiovascular medicine: From stem cell biology to precision medicine

Engineering functional human vasculature: iPSC-derived vascular cells and organoids for disease modeling and translation.

Human vascular function depends on tightly coordinated structural, mechanical, and cellular interactions, yet these features remain difficult to recapitulate in vitro. Induced pluripotent stem cells (iPSCs) enable efficient generation of vascular cell types, including endothelial cells, smooth muscle cells, and pericytes, but current systems often lack functional maturity and physiological relevance. Recent advances in vascular organoid engineering provide new opportunities to address this limitation. By integrating self-organization, co-culture, and bioengineering approaches, iPSC-derived systems can form three-dimensional vascular networks with increasing physiological relevance. Emerging evidence from studies of iPSC-derived vascular systems, spanning both two-dimensional differentiation models and three-dimensional organoid platforms, highlights the critical roles of hemodynamic cues, including shear stress and perfusion, together with metabolic and immune signaling, in driving the coordinated maturation of endothelial and mural compartments. These platforms enable modeling of key vascular pathologies, including inflammation, vascular remodeling, and barrier dysfunction, while gene editing further facilitates mechanistic investigation in patient-specific contexts. Together, iPSC-derived vascular systems provide a scalable and physiologically relevant platform for disease modeling, drug discovery, and regenerative medicine.

Emerging Role of Human Organoids in Drug Discovery and Development: Current Advances and Challenges

Nanomaterial-Mediated Stem Cells Fate Regulation: From Mechanism of Action to Regenerative Medicine Applications

Stem cells possess self-renewal capacity and differentiation potential. Under appropriate conditions, they can continuously divide to generate more stem cells of the same type or differentiate into various specialized cell types, thereby contributing to the formation of diverse tissues and organs. In tissue engineering and regenerative medicine, stem cells serve as key elements for repairing or replacing functional tissues lost due to disease, injury, or aging. The development of nanomaterials has provided new tools and approaches for stem cell research, particularly in the biomedical field, where they are widely applied in drug delivery, biosensing, medical imaging, and tissue engineering. Moreover, through interactions with cell membranes and/or intracellular components, nanomaterials can modulate key stem cell functions — including differentiation, proliferation, and adhesion — thereby enhancing the therapeutic efficacy of stem cells in biomedical applications. This review first introduces the main characteristics and potential risks associated with the application of nanomaterials to stem cells. The subsequent section provides an overview of how nanomaterials regulate stem cell biological functions and activate associated signaling pathways, followed by a discussion of future directions and challenges in this field.

Function-First Organoid Engineering for Regenerative Medicine: Current Challenges and Future Perspectives.

A function-first framework in which regenerative organoids are engineered and evaluated according to measurable therapeutic outcomes, including tissue-specific function, vascular integration, immune compatibility, reproducibility, scalability, and long-term stability is proposed.

Generation of synthetic vascular organoids via orthogonal programming of human pluripotent stem cells

The development of functional human vasculature is essential for tissue engineering, disease modeling, and regenerative medicine. Conventional differentiation protocols of vascular lineages often exhibit lineage heterogeneity and limited control over cellular ratios. Here, we describe a protocol for generating vascular organoids (VOs) via orthogonal forward programming of hPSCs. By utilizing doxycycline-inducible activation of the transcription factors ETV2 and NKX3.1, hPSCs are rapidly directed toward endothelial and mural cell lineages, respectively. This strategy enables the assembly of VOs with precisely tunable cellular compositions within six days. When combined with fluorescent reporter lines (PECAM1-mRuby3 and ACTA2-EGFP), vascular networks can be visualized in real time without the need for tissue clearing or immunostaining. We detail procedures for stable cell line engineering, 3D organoid assembly, in vitro angiogenesis assays for drug screening, and in vivo transplantation under the mouse kidney capsule to form perfusable human vasculature. This platform provides a flexible, standardized, and scalable tool for investigating vascular biology, modeling inherited vasculopathies, and enhancing the vascularization of co-transplant tissues.

Harnessing stem cells for regenerative medicine: Current applications and future prospects

Background: Degenerative diseases place an immense burden on global healthcare. Stem cell-based regenerative medicine offers transformative, potentially curative therapies to restore damaged tissues and recover normal physiological function. Aim: This review aims to comprehensively evaluate the therapeutic applications, biological mechanisms, and clinical prospects of stem cells in treating diverse human organ disorders. Methods: We conducted a comprehensive literature review of preclinical models and clinical trials focusing on mesenchymal (MSCs), hematopoietic (HSCs), and pluripotent stem cells (PSCs), evaluating their efficacy, safety, and manufacturing challenges. Results: Cell therapies demonstrate remarkable healing potential. MSCs exhibit potent immunomodulatory effects in inflammatory conditions. HSC transplantation remains the gold standard for hematological disorders and is expanding into targeted gene therapies. PSC-derived cells show promising clinical efficacy in spinal cord injuries, macular degeneration, type 1 diabetes, and heart failure. However, significant hurdles remain, including immune rejection, tumorigenicity, and batch-to-batch variability. Conclusion: Cell therapies represent a paradigm shift from lifelong symptom management to definitive cures. Resolving biological, technical, and regulatory hurdles is imperative for the safe, standardized, and widespread clinical translation of these interventions. Relevance for Patients: For patients suffering from chronic, degenerative, or currently incurable conditions, stem cell therapies represent a transformative clinical paradigm. By facilitating functional tissue regeneration and targeted immunomodulation, these therapies reduce the burden of chronic pharmacotherapy and invasive procedures.