Gu et al. present NEAT, a nanoengineered extrusion-aligned tract bioprinting strategy that fabricates aligned, human neural stem cell-laden collagen hydrogel constructs through shear-induced fibrillar organization. In a rat model of complete spinal cord transection, NEAT enables axonal reconnection and functional locomotor recovery, demonstrating its translational potential for spinal cord repair and neural tissue engineering.

Paulsen et al. present the process development and clinical application of an hiPSC-derived OSC product, Fertilo. They describe the raw material upgrades, process consistency and reproducibility, and analytical assessment required for the generation of a clinically suitable product, as well as favorable outcomes from the first-in-human application of Fertilo.

Bartram et al. show that HSCs with accrued divisions generate low-output progeny that are highly variable in lineage distribution and transcriptionally divergent within individual lineages. HSC functional decline arises from redirecting BCAA usage from catabolic toward anabolic activity. BCAA metabolite replacement restores division-dependent HSC fitness.

Sharma et al. present a bioengineered retinal organoid system that supports long-term survival and functional maturation of retinal ganglion cells through transient vascular support and microfluidic guidance. The platform sustains neuronal activity and enables circuit-level light responses in advanced human retinal models.

Liu et al. generate human sympathetic ganglion organoids and assemble them with heart-forming organoids to build functionally connected sympathetic-cardiac organoids in vitro. Their platform captures autonomic development, neuromodulation of heart function, and metabolic injury, opening new opportunities to study human autonomic disorders and cardiometabolic disease.

Human pineal development and neuroendocrine regulation remain incompletely understood at the molecular and functional levels. Kiral et al. establish human pineal gland organoids (hPGOs) that recapitulate pinealocyte maturation, noradrenergic responsiveness, and melatonin synthesis, providing a platform for investigating circadian dysfunction and disease-associated sleep disturbances.

In this issue of Cell Stem Cell, Zhang et al. identify a pathological NTRK2 isoform switch in bronchopulmonary dysplasia that alters the regenerative capacity of capillary endothelial cells, highlighting isoform-specific targeting as a promising strategy for vascular repair.

Editors’ note: The Ogawa-Yamanaka Stem Cell Prize recognizes groundbreaking work in translational regenerative medicine using reprogrammed cells. The prize is supported by Gladstone Institutes, in partnership with Cell Press. Among his myriad accomplishments, Rudolf Jaenisch—winner of the 2025 Ogawa-Yamanaka Stem Cell Prize—was the first to demonstrate the potential of induced pluripotent stem cells to treat disease.

This perspective highlights anti-aging strategies with an emphasis on the partial reprogramming approach for cellular rejuvenation and extending healthspan. It also discusses the use of ex vivo perfusion technology to help bring innovative therapies, like partial reprogramming, into clinical practice.

Wang et al. show that grafted cortical neurons reconstitute the ischemic cortex while extending specific projections and forming functional synapses with host neurons in the brain and spinal cord. Projections are segregated by transcriptional subtypes, revealing intrinsic transcriptional programs that encode projection preferences and enable subtype-specific circuit integration during repair.

Jones et al. demonstrate that Notch signaling suppresses CD4+ (helper) T cell induction from PSCs and that manipulating TCR and Notch signaling enables control over CD4+ vs. CD8+ (cytotoxic) T cell production. The resulting PSC-CD4+ T cells achieve a naive/memory phenotype and are capable of functional Th1/2/17 polarization.

Kiral and colleagues develop human pineal gland organoids (hPGOs) that produce melatonin, respond to noradrenergic signaling, and restore circulating levels in pinealectomized mice. They demonstrate that UBE3A deficiency in Angelman syndrome disrupts pinealocyte maturation and impairs melatonin synthesis, establishing a robust human model for investigating pineal biology and sleep dysfunction.

Endo et al. show that preserving the intestinal niche enables near-complete engraftment of ileal organoids in the jejunum. The resulting ilealized segment restores bile acid absorption and improves survival in short bowel syndrome, suggesting a path toward region-targeted, autologous regenerative therapy.

Zhang et al. uncover a pathological NTRK2 isoform switch in gCaps that impairs vascular regeneration in bronchopulmonary dysplasia. Restoring full-length NTRK2 reverses vascular and alveolar defects in hyperoxic lung injury. These findings highlight isoform-specific NTRK2 targeting as a promising regenerative strategy.

Zhao and colleagues develop a 3D co-culture system of human embryo and endometrium that mirrors post-implantation development, revealing key signaling events at the maternal-embryonic interface relevant to early pregnancy success.

Dysplastic KRT5+ basal-like cells emerge in alveoli across lung diseases, yet their role in disease progression remains unclear. Xi and colleagues demonstrate that KRT5+ cells impair alveolar regeneration by interacting with and retaining T cells in the lung post viral infection. Tissue-resident T cells inhibit club-to-AT2 differentiation to impair lung repair.

Glass, Matoba, et al. demonstrate that human cortical organoid cell-type proportions, cross-sectional area growth, and cell cycle genes in early neural progenitors are associated with inter-individual variability in infant cortical surface area measurements, supporting the fidelity of organoids as a model system.

Sympathetic ganglia control vital body functions, yet their modeling is challenging. Xiang and colleagues developed hPSC-derived organoids that recapitulate the sympathetic ganglia and their functional connection with the heart. These findings provide a model for studying human sympathetic ganglia, sympathetic control of target organs, and related diseases.

Human pluripotent stem cells offer a scalable platform for generating immune effector cells with enhanced anti-tumor potential. This review explores recent advances in hPSC-derived NK cells, T cells, and macrophages, highlighting strategies to overcome immunogenicity, toxicity, and scalability challenges in allogeneic cancer immunotherapy.

Preserving the functionality of hematopoietic stem cells during ex vivo manipulation for clinical applications remains a challenge. Here, Midena et al. implement a nanoengineered 3D culture substrate compatible with multiple gene therapy platforms that enhances the engraftment and clonal output of engineered cells through biomechanical regulation of stem cell properties.

Repair glia in peripheral nerves are part of a regenerative niche in acute skin wounds. This glial niche promotes skin wound healing by regulating innate immune cell recruitment, in particular monocytes and monocyte-derived macrophages, both critical for a successful repair process.

(Cell Stem Cell 31, 1162–1174.e1–e9; August 1, 2024)

Kiral and colleagues develop human pineal gland organoids (hPGOs) that produce melatonin, respond to noradrenergic signaling, and restore circulating levels in pinealectomized mice. They demonstrate that UBE3A deficiency in Angelman syndrome disrupts pinealocyte maturation and impairs melatonin synthesis, establishing a robust human model for investigating pineal biology and sleep dysfunction.

Endo et al. show that preserving the intestinal niche enables near-complete engraftment of ileal organoids in the jejunum. The resulting ilealized segment restores bile acid absorption and improves survival in short bowel syndrome, suggesting a path toward region-targeted, autologous regenerative therapy.

Zhang et al. uncover a pathological NTRK2 isoform switch in gCaps that impairs vascular regeneration in bronchopulmonary dysplasia. Restoring full-length NTRK2 reverses vascular and alveolar defects in hyperoxic lung injury. These findings highlight isoform-specific NTRK2 targeting as a promising regenerative strategy.