Tatsuto Kageyama

Development of hair follicle clone for cultured animal fiber engineering

Grant No.：JPMJPR2531

Researcher : Tatsuto Kageyama

Outline

This research aims to elucidate the mechanisms of the hair cycle and fabricate hair follicle clone that repeatedly undergo the hair cycle in vitro. The hair follicle clone will open new avenues to establish a technology for cultured animal fiber engineering.

Yuki Kanai

“Breeding” supra-biological tissues by engineering evolvability

Grant No.：JPMJPR2532

Researcher : Yuki Kanai

Outline

We humans have obtained diverse and complex biological tissues through breeding. In contrast, artificially designed biological tissues still remain simple in form. In this study, we will create an E. coli strain with high “evolvability” by introducing gene circuits that serve as the basis of morphological evolution, and “breed” tissues that exhibit complex fluorescent patterns. By integrating synthetic biology, evolutionary biology, and genome analysis to understand and control the evolvability of multicellular populations, this study aims to pioneer the “breeding science of supra-biological tissues.”

Taisuke Kondo

Supraphysiologic adaptive artificial immunity

Grant No.：JPMJPR2533

Researcher : Taisuke Kondo

Outline

This project aims to build an artificial immune system that autonomously adapts to dynamic in vivo environments by designing engineered immune cells with synthetic genetic circuits. Using high-throughput profiling and prediction models, the behavior of this multicellular system will be analyzed to understand general design principles for in vivo adaptation. This adaptive immune-cell platform could provide a conceptual strategy for next-generation cancer immunotherapy.

Ryota Sakamoto

Engineering Designer Artificial Tissues through Active Cytoskeletal Control

Grant No.：JPMJPR2534

Researcher : Ryota Sakamoto

Outline

This study aims to develop “Designer Artificial Tissues” whose physical and chemical properties can be flexibly engineered beyond the constraints of biological evolution. By integrating key cellular components - lipid membranes, cytoskeleton, and cytoplasm - we will construct artificial tissues and measure their light-controlled contraction-relaxation responses and energy conversion efficiency. We will further elucidate the molecular alignment and non-equilibrium wave dynamics within artificial tissues, and leverage optical control to drive three-dimensional structure formation and wound healing functions. Through this approach, we seek to establish a foundation for designing hybrid tissues that combine biological and artificial elements, and for bio-robots with self-repairing capabilities.

Kenta Shimba

Building Functional Spinal Cord Circuits on a Chip through Dynamic Sensory Input Control

Grant No.：JPMJPR2535

Researcher : Kenta Shimba

Outline

This project will apply a combination of engineering tools and biological methods to reproduce spinal cord circuits in culture by controlling sensory input in real time. Non-invasive measurements will determine the type, connections, and maturity of each cell and guide precise stimulation of sensory neurons. Such stimulation is expected to help cultured spinal cord tissue develop functions similar to those in living organisms. The project will explore strategies to implement reduced pain signaling and enhanced important touch signaling in cultured spinal cord circuits. These studies aim to establish approaches for building tissues that exceed the functions of natural systems.

Shunsuke Tanigawa

Creating functional kidney organoids with the next-generation embryo culture system “Embryo in CUBE”

Grant No.：JPMJPR2536

Researcher : Shunsuke Tanigawa

Outline

Organoids derived from human iPS cells still require further technological advances before they can be applied to transplantation medicine. This study aims to develop a next-generation culture system, “Embryo in CUBE,” which recreates the fetal environment in vitro, enabling embryos to grow and organs to mature, by combining stem cell biology and bioengineering. This system is designed to confer kidney organoids with functional properties, and its outcomes could also have a significant impact on organoids of other organs, contributing to the advancement of pluripotent stem cell–derived organ transplantation and the modeling of late-onset diseases.

Rio Tsutsumi

Decoding Cellular Programs toward Programmable Mesenchymal Morphogenesis

Grant No.：JPMJPR2537

Researcher : Rio Tsutsumi

Outline

This project targets mesenchymal tissue morphogenesis, seeking principles to design and control macroscopic tissue morphogenesis from cell-level self-organizing programs. I will model limb skeletal morphogenesis by integrating organoids with quantitative analysis, using limb mesenchyme differentiated from ES/iPS cells of mouse, human, and other species. By comparing species-specific “programs” of morphogenesis and calibrating in silico models, we will identify a minimal set of parameters that govern morphological diversity. These parameters will provide levers to predict, design, and control tissue shape. The resulting framework will unify micro-to-macro causality in morphogenesis and establish design rules for engineering diverse tissue architectures.

MINGHAO NIE

Development of cultured skin integrating a three-dimensional flexible substrate and capillary vessel network

Grant No.：JPMJPR2538

Researcher : MINGHAO NIE

Outline

In recent years, cultured skin has advanced rapidly toward applications such as regenerative medicine and drug evaluation, yet challenges remain in nutrient supply for long-term maintenance of tissue morphology and function. This project aims to engineer three-dimensional cultured skin with an integrated capillary network on a flexible substrate, enabling both efficient nutrient delivery and mechanical responsiveness. This biofabrication approach is expected to provide a versatile platform for investigating skin mechanobiology, advancing cosmetic development, and serving as covering materials for biohybrid robots.

Koichiro Hayashi

Creation of an Active ‘Super’ Bone–Marrow Unit for Disease Control

Grant No.：JPMJPR2539

Researcher : Koichiro Hayashi

Outline

This study aims to optimize the micro- and nanostructures of carbonate apatite honeycomb materials and to elucidate the mechanisms underlying the formation of a “super” bone–marrow possessing both hematopoietic and immune functions. In addition, by integrating these materials with multicellular populations derived from dental pulp, we seek to establish an innovative strategy to generate such constructs rapidly and noninvasively. Furthermore, we intend to realize this construct as an “active super-biomimetic tissue” that can proactively regulate immune responses from the initial stage of implantation. Ultimately, this research pursues its application as a preventive therapeutic approach against medication-related osteonecrosis of the jaw, an intractable disease that remains a major clinical challenge.

Takehiro Hiraoka

Deciphering and regulating embryo implantation using an ex vivo uterine system

Grant No.：JPMJPR253A

Researcher : Takehiro Hiraoka

Outline

This study addresses the fundamental challenge that embryo implantation occurs deep within the maternal body and cannot be directly observed. To overcome this limitation, the research will advance an ex vivo uterine system previously established by the applicant, with a particular focus on oxygen supply and scaffold to faithfully reproduce implantation ex vivo. The platform will be employed to investigate cell type–specific functions through chemical perturbations and targeted gene delivery, while elucidating how modulation of multicellular interactions governs implantation dynamics. These efforts are expected to yield mechanistic insights into implantation and ultimately contribute to the identification of diagnostic markers and the development of replacement therapies, paving the way for innovative implantation-assisting technologies in assisted reproductive technology.

Shinji Miyata

Engineering a super-biological brain with human-like giant neurons

Grant No.：JPMJPR253B

Researcher : Shinji Miyata

Outline

In this study, I aim to construct an engineered super-biological brain by inducing the formation of giant human-like neurons within the mouse brain. The key lies in the extracellular matrix surrounding neurons, known as the perineuronal net, whose artificial regulation enables remodeling of neuronal structure and function. Furthermore, I will apply this technology to neurodegenerative disease models to create engineered super-biological tissues capable of reproducing human-specific pathological features that conventional models have failed to mimic.

Maho Yagi

Creation of desiccation-tolerant supra-biological tissues pioneered by tardigrade proteins

Grant No.：JPMJPR253C

Researcher : Maho Yagi

Outline

I aim to create desiccation-tolerant supra-biological tissues inspired by the remarkable desiccation tolerance of tardigrades. In this project, I will focus on tardigrade proteins and elucidate how supramolecular networks preserve intercellular adhesion and structural stability. Building on these insights, I will design and construct artificial networks and introduce them into living cells to test and refine their functions. By comprehensively analyzing the functional interactions among tardigrade proteins and the molecular networks that strengthen cell adhesion, I will establish and demonstrate artificial systems capable of stabilizing cellular and tissue structures under desiccation and rehydration conditions.