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Open research questions in Pluripotent Stem Cells Research

200 unresolved questions extracted from the limitations and future-work sections of 447 Pluripotent Stem Cells Research papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • One of the main limitations of current models is their reproducibility. The paper identifies the need for standardization and consensus standards to ensure reproducibility. The paper also identifies the need for nuanced ethical frameworks that account for the fast-paced advancements of stem cell science.

    Human stem cell-based embryo models: innovation, ethics, and policy · 2026 · DOI

  • reproducibility of current models is a main limitation, - experimental conditions such as culture media and starting cell line can affect results, - lack of proper models that reflect human development is a limitation

    Human stem cell-based embryo models: innovation, ethics, and policy · 2026 · DOI

  • Investigating graft survival, differentiation and functional integration, - Examining the mechanisms of iPSC-based therapies in the CNS, - Conducting larger studies to confirm the safety and efficacy of iPSC-NS/PC transplantation

    An iPSC-derived neural progenitor cell therapy for subacute spinal cord injury: a phase 1 trial with long-term follow-up · 2026 · DOI

  • The safety of iPSC-NS/PC transplantation in humans is unknown. There is a lack of clinical evidence for the feasibility and safety of this approach. The study aims to address this gap by providing clinical evidence for the safety and efficacy of iPSC-NS/PC transplantation.

    An iPSC-derived neural progenitor cell therapy for subacute spinal cord injury: a phase 1 trial with long-term follow-up · 2026 · DOI

  • Following terminal differentiation, however, cellular identities become remarkably stable and resistant to TF-mediated perturbation, yet the mechanisms underlying this stability remain poorly understood.

    Polycomb establishes TAD-scale H3K27me3 mega-domains to safeguard neuronal identity · 2026 · DOI

  • Although classical embryological studies suggested that developmental progression can occur independently of normal cell division, the extent to which DNA replication contributes to these processes remains unclear.

    DNA replication is dispensable for developmental progression, but required for heterochromatin organization at mouse zygotic genome activation · 2026 · DOI

  • This work reveals impacts of UBE3A on understudied cell types and related neurodevelopmental processes and elucidates potential therapeutic targets.

    Loss of UBE3A impacts both neuronal and non-neuronal cells in human cerebral organoids · 2025 · DOI

  • Human cerebral organoids might reveal these understudied aspects of UBE3A as they recapitulate diverse cell types of the developing human brain.

    Loss of UBE3A impacts both neuronal and non-neuronal cells in human cerebral organoids · 2025 · DOI

  • Even though both approaches are potentially lifesaving, their application and development are currently limited by a range of medical and ethical issues.

    Rescue by the Self and a Fellow Human: Transplantation and Stem Cells · 2024 · DOI

  • The proneural factor NGN2 has been shown to overcome experimental variability observed by morphogen-guided differentiation and directly converts pluripotent stem cells into neurons, but their cellular heterogeneity has not been investigated yet.

    Generation of human excitatory forebrain neurons by cooperative binding of proneural NGN2 and homeobox factor EMX1 · 2024 · DOI

  • Conclusions While genetic silencing of the pacemaker ion channel HCN4 suppresses the automaticity of hPSC-CMs in vitro, this intervention is insufficient to reduce VT risk post-transplantation in the pig MI model, implying more complex mechanism(s) are operational in vivo.

    Stem cell-derived cardiomyocytes expressing a dominant negative pacemaker HCN4 channel do not reduce the risk of graft-related arrhythmias · 2024 · DOI

  • In the case of the brain, the effects of partial reprogramming are scarcely known, and only some of its effects have been observed through the widespread expression of YF.

    In vivo cyclic overexpression of Yamanaka factors restricted to neurons reverses age-associated phenotypes and enhances memory performance · 2024 · DOI

  • While there is a good understanding of the molecular regulatory network maintaining ES pluripotency, the process by which pluripotent ESCs reprogram into totipotent cells and the associated molecular mechanisms of totipotent regulation remain poorly understood.

    Advances in understanding the regulation of pluripotency fate transition in embryonic stem cells · 2024 · DOI

  • However, the exact roles of ERK1/2 in mouse ESC self-renewal and differentiation remain unclear.

    A novel chemical genetic approach reveals paralog-specific role of ERK1/2 in mouse embryonic stem cell fate control · 2024 · DOI

  • This study aims to provide an overview of the workflow for iPSC induction, comparing well-established protocols in humans and mice with the limited information available for avian species.

    Avian iPSC Derivation to Recover Threatened Wild Species: A Comprehensive Review in Light of Well-Established Protocols · 2024 · DOI

  • The high metabolic cost of the therapy. The need for 24-hour residency in a controlled clinical environment. The requirement for careful screening for pre-existing syndromes or chronic immunological conditions.

    "Integrated Chemotherapeutic Reprogramming and Targeted Senotherapeutic Clearance Elicits Near-Complete (80–89%) Restoration of Youthful Multi-Omic Profiles and Systemic Physiological Resilience." · 2026 · DOI

  • Further study of the effects of the therapy on age-related diseases. Investigation of the potential for the approach to be used in conjunction with other therapies.

    "Integrated Chemotherapeutic Reprogramming and Targeted Senotherapeutic Clearance Elicits Near-Complete (80–89%) Restoration of Youthful Multi-Omic Profiles and Systemic Physiological Resilience." · 2026 · DOI

  • The inability of single-cell transcriptome sequencing technology to resolve spatial positional information. The lack of understanding of the molecular mechanisms governing PGC specification into oogonia.

    A spatiotemporal transcriptomic atlas of porcine (Sus scrofa) female early gonadal development · 2026 · DOI

  • The mechanisms that underlie TE and blastocoel morphogenesis are poorly understood. The potential of human blastoid models to uncover fundamental mechanisms of early human development remains limited.

    A single small molecule-based human embryo model reveals V-ATPase requirement in mammalian blastocyst cavitation · 2026 · DOI

  • The V-ATPase knockdown assay was performed using transcriptomic analysis, but the paper does not include a dose-response study with varying degrees of V-ATPase inhibition (partial versus complete knockdown) to determine whether cavitation exhibits a threshold-dependent response or linear relationship with V-ATPase activity.

    A single small molecule-based human embryo model reveals V-ATPase requirement in mammalian blastocyst cavitation · 2026 · DOI

  • Short-and long-term goals in the field of regenerative RNA nanomedicine need to be addressed. The call to action for regenerative RNA nanomedicine is to change the face of regenerative medicine in the coming years.

    Advancing regenerative medicine with RNA nanotechnology for chronic and end organ diseases · 2026 · DOI

  • There is a need for alternate therapeutic options for patients who are ineligible for organ transplantation. The development of safe and efficacious regenerative medicine is challenging.

    Advancing regenerative medicine with RNA nanotechnology for chronic and end organ diseases · 2026 · DOI

  • Interspecies differences limit the direct extrapolation of findings from animal models to human physiology. Two-dimensional culture systems lack three-dimensional cell-extracellular matrix interactions. The use of biologically derived extracts in hiPSC culture can result in significant heterogeneity.

    From chemically defined hiPSCs to self-organizing cardiac organoids: current strategies guided by developmental signaling · 2026 · DOI

  • Further studies are needed to fully explore the potential of cardiac organoids. Research should focus on the development of more advanced hiPSC culture systems and the identification of key developmental signaling pathways. The use of cardiac organoids in precision cardiovascular medicine should be further investigated.

    From chemically defined hiPSCs to self-organizing cardiac organoids: current strategies guided by developmental signaling · 2026 · DOI

  • The involvement of more than one cell in the initiation of oncogenesis is not fully understood. The mechanisms of activation of the early totipotent program by unselective stem cell fusion are not well explored.

    On the potential origin of the zygote-like cancer stem cell with a focus on fusion for cell rescue · 2026 · DOI

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200 open questions have been extracted from the limitations and future-work passages of 447 Pluripotent Stem Cells Research papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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