Engineering the future of advanced therapy medicinal products: a bioengineering call to action

Future Directions in Stem Cells, Cell Therapy, and Bioengineering in Lung Biology and Diseases.

Over the past two decades, progress in stem cell biology, bioengineering, and systems biology has improved our understanding of lung regeneration and repair. Building on work presented at the 20th Anniversary Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases Conference, this review examines the evolving trajectory of the field and outlines remaining challenges and opportunities for future research. We focus on three main areas: improving ex vivo lung models to better capture cellular heterogeneity and biomechanics; using single-cell, spatial, and computational approaches to support translation into clinical practice; and innovative therapeutic strategies, including gene therapies, epithelial cell therapies, immune cell engineering, extracellular matrix reconditioning, senescence targeting, and whole-organ bioengineering and xenotransplantation. Together, these approaches are shifting lung regeneration from descriptive studies toward precision, mechanism-driven therapies. Future progress in lung regenerative medicine will require integration of omics-driven insights with functional validation and biomaterial innovation to achieve meaningful clinical impact.

Clinical landscape of human pluripotent stem cell-derived cardiomyocyte therapy.

Heart failure is a major clinical and economic burden that afflicts 60 million individuals worldwide. Guideline-directed medical therapies can slow disease progression, but they cannot restore the loss of cardiomyocytes. Over the past two decades, human pluripotent stem cell (hPSC)-based technology has emerged as a leading approach to overcome limited cardiac regenerative capacity, offering a scalable source of functional human cardiomyocytes. The field is now at a pivotal translational stage, as advances in differentiation and tissue engineering have enabled hPSC-based products to enter first-in-human clinical trials. In this review, we summarize the pathophysiological rationale for cell-based therapy in heart failure with reduced ejection fraction. Then, we examine the preclinical foundations of distinct hPSC-derived product formats, including cell suspensions, epicardial sheets, engineered heart muscle, and cardiac spheroids, each with distinct tradeoffs and translational considerations. We conclude by providing updates on ongoing and recently completed clinical trials, evaluating their safety, feasibility, and preliminary efficacy outcomes.

Engineering Mesenchymal Stem Cells for Healthspan-Relevant Applications: Therapeutic Potential, Challenges, and Future Solutions

Highlights What are the main findings? In various clinical trials, largely unmodified mesenchymal stem cell (MSC) therapies have shown limited and inconsistent benefits, highlighting the need for a shift toward MSC products engineered to target specific mechanisms and diseases. Targeted engineering, such as genetic modification, hematopoietic cell E-/L-selectin ligand (HCELL)/CD44 and E-selectin glycoengineering, hypoxic/cytokine preconditioning, biomaterial scaffolding, and MSC-derived extracellular vesicles, may address core limitations of unmodified MSCs by improving homing, persistence, immunomodulation, and resistance to senescence in preclinical models, which may in turn contribute to healthspan-relevant outcomes. What are the implications of the main findings? Disease-matched and combinatorial engineering could establish MSCs as a flexible therapeutic platform for treating age-related diseases and potentially improving healthspan-related outcomes rather than lifespan alone. Clinical translation will depend on standardized manufacturing, validated potency and senescence resistance assays, long-term monitoring of tumorigenicity, and regulatory frameworks suited to aged recipients. Abstract Engineered mesenchymal stem cells (MSCs) have emerged as promising therapeutic platforms for healthspan-relevant applications. As agents of tissue repair and modulators of biological aging, MSCs have been widely studied for their capacity to enhance regeneration, restore immune homeostasis, and reduce chronic inflammation associated with age-related decline. This review examines emerging bioengineering strategies designed to overcome key age-related limitations in MSC homing, survival, and paracrine signaling, which have historically constrained their in vivo efficacy. We discuss major engineering approaches, including genetic modification, surface engineering, metabolic reprogramming, and preconditioning, with particular attention to their contributions to longevity-focused applications. Preclinical studies have demonstrated that engineered MSCs and their extracellular vesicles (EVs) yield measurable improvements in therapeutic performance. Reported benefits include prolonged persistence in inflamed tissues, partial reversal of senescence-associated phenotypes, and modulation of pro-aging inflammatory pathways. While MSC-derived EVs may offer potential safety advantages and could reduce certain risks associated with live-cell administration, this remains to be confirmed in well-controlled clinical studies, and significant challenges persist in terms of manufacturing scalability, cargo consistency, and process standardization. The current literature, which is predominantly preclinical, supports the potential of engineered MSC platforms to improve healthspan-relevant outcomes; direct evidence of healthspan extension in humans is not yet available. However, successful clinical translation will require a standardized manufacturing process to ensure therapeutic safety, reproducibility, and efficacy in age-related conditions.

Manufacturing as biology: How T-cell processing shapes therapeutic outcomes.

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

A comprehensive literature review of preclinical models and clinical trials focusing on mesenchymal, hematopoietic, and pluripotent stem cells, evaluating their efficacy, safety, and manufacturing challenges found stem cell therapies demonstrate remarkable healing potential.

Applications of synthetic biology in biomedicine

This review systematically summarizes progress in foundational tools and key supporting technologies of synthetic biology, highlights innovative strategies and clinical value in biosensors, cell therapy, living therapeutics, and smart biomaterials, and provides an in-depth comparison of different chassis cells, delivery vectors, and regulatory circuits in terms of disease suitability, safety, and translational efficiency.