Volume 3, Issue 4 - Special Issue on Stem Cell and Regenerative Medicine

The remarkable similarity between non-human primates (NHPs) and humans establishes them as essential models for understanding human biology and diseases, as well as for developing novel therapeutic strategies, thereby providing more comprehensive reference data for clinical treatment. Pluripotent stem cells such as embryonic stem cells and induced pluripotent stem cells provide unprecedented opportunities for cell therapies against intractable diseases and injuries. As continue to harness the potential of these biotechnological therapies, NHPs are increasingly being employed in preclinical trials, serving as a pivotal tool to evaluate the safety and efficacy of these interventions. Here, we review the recent advancements in the fundamental research of stem cells and the progress made in studies involving NHPs.

Natural killer (NK) cells possess innate abilities to effectively eliminate cancer cells. However, because of difficulties of proliferation and easy to be induced dysfunction in the setting of cancer post NK cell therapy, the curative effect of NK cell infusion has been constrained and not been widely applicable in clinical practice. The rapid development of biotechnology has promoted the development of NK cell therapy for cancer treatment. In this review, we will provide a comprehensive analysis of the current status and future prospects of NK cell therapy for cancer, focusing on the biological characteristics of NK cells, as well as strategies to enhance their targeting capabilities and overcome tumor immune suppression within the microenvironment.

Intelligent nanomedicine is currently one of the most active frontiers in cancer therapy development. Empowered by the recent progresses of nanobiotechnology, a new generation of multifunctional nanotherapeutics and imaging platforms has remarkably improved our capability to cope with the highly heterogeneous and complicated nature of cancer. With rationally designed multifunctionality and programmable assembly of functional subunits, the in vivo behaviors of intelligent nanosystems have become increasingly tunable, making them more efficient in performing sophisticated actions in physiological and pathological microenvironments. In recent years, intelligent nanomaterial-based theranostic platforms have showed great potential in tumor-targeted delivery, biological barrier circumvention, multi-responsive tumor sensing and drug release, as well as convergence with precise medication approaches such as personalized tumor vaccines. On the other hand, the increasing system complexity of anti-cancer nanomedicines also pose significant challenges in characterization, monitoring and clinical use, requesting a more comprehensive and dynamic understanding of nano-bio interactions. This review aims to briefly summarize the recent progresses achieved by intelligent nanomaterials in tumor-targeted drug delivery, tumor immunotherapy and temporospatially specific tumor imaging, as well as important advances of our knowledge on their interaction with biological systems. In the perspective of clinical translation, we have further discussed the major possibilities provided by disease-oriented development of anti-cancer nanomaterials, highlighting the critical importance clinically-oriented system design.

Studying human development remains difficult due to limited accessibility to human embryonic tissues. Prompted by the availability of human stem cells that share molecular and cellular similarities with embryonic and extraembryonic cells in peri-implantation human embryos, researchers have now successfully developed stem cell-based human embryo models that are promising as experimental tools for studying early human development. In this Perspective, we discuss the current progress in mouse and human stem cell-derived embryo models and highlight their promising applications in advancing the fundamental understanding of mammalian development.

Neuropsychiatric disorders (NPD) are prevalent and devastating, posing an enormous socioeconomic burden to modern society. Recent genetic studies of NPD have identified a plethora of common genetic risk variants with small effect sizes and rare risk variants of high penetrance. While exciting, there is a pressing need to translate these genetic discoveries into better understanding of disease biology and more tailored clinical interventions. Human induced pluripotent stem cell (hiPSC)-derived 2D and 3D neural cultures are becoming a promising cellular model for bridging the gap between genetic findings and disease biology for NPD. Leveraging the accessibility of patient biospecimen to convert into stem cells and the power of genome editing technology to engineer disease risk variants, hiPSC model holds the promise to disentangle the disease polygenicity, model genetic interaction with environmental factors, and uncover convergent gene pathways that may be targeted for more tailored clinical intervention.

Lipid-based nanoparticles (LNP) have shown significant progress in delivering mRNA for therapeutics, particularly with the success of coronavirus disease 2019 (COVID-19) vaccines. However, there are still challenges, such as organ-specific targeting, sustained protein expression, immunogenicity, and storage that need to be addressed. Therefore, there is interest in developing additional nano drug delivery systems (DDS) to complement LNP technology. Some of these include polymer, lipid-polymer hybrid, organic/inorganic hybrid nanostructure, and inorganic nanoparticle. In our opinion, LNP technology may not be suitable for every disease scenario in categories such as infection disease, cancer, pulmonary disease, autoimmune disorders and genetic rare disease (among others). This is because different diseases may require distinct administration routes, doses, and treatment durations, as well as considerations for biological barriers that may lower the efficacy and/or exert safety concern. In this perspective, we will highlight the need and potential for enhancing the diversity of nano delivery platforms for mRNA-based nanotherapeutics.