Stem cell transplantation extends the reproductive life span of naturally aging cynomolgus monkeys.

The ovary is crucial for female reproduction and health, as it generates oocytes and secretes sex hormones. Transplantation of mesenchymal stem cells (MSCs) has been shown to alleviate pathological ovarian aging. However, it is unclear whether MSCs could benefit the naturally aging ovary.

Single-cell RNA sequencing reveals transcriptomic landscape and potential targets for human testicular ageing.

Study Question: What is the molecular landscape underlying the functional decline of human testicular ageing?

Summary Answer: The present study provides a comprehensive single-cell transcriptomic atlas of testes from young and old humans and offers insights into the molecular mechanisms and potential targets for human testicular ageing.

What Is Known Already: Testicular ageing is known to cause male age-related fertility decline and hypogonadism. Dysfunction of testicular cells has been considered as a key factor for testicular ageing.

Deficiency of SECTM1 impairs corneal wound healing in aging.

The corneal epithelium is the outermost transparent barrier of the eyeball and undergoes continuous self-renewal by limbal stem cells (LSCs) during its lifetime; however, the impact of aging on LSCs remains largely unknown. Here, we showed that the healing ability of the cornea in elderly macaques (Macaca fascicularis) was significantly decreased compared to that of younger macaques. This delayed wound closure accompanied a disordered cell arrangement and corneal opacity.

AAV-mediated gene therapy restores natural fertility and improves physical function in the Lhcgr-deficient mouse model of Leydig cell failure.

Leydig cell failure (LCF) caused by gene mutations leads to testosterone deficiency, infertility and reduced physical function. Adeno-associated virus serotype 8 (AAV8)-mediated gene therapy shows potential in treating LCF in the Lhcgr-deficient (Lhcgr) mouse model. However, the gene-treated mice still cannot naturally sire offspring, indicating the modestly restored testosterone and spermatogenesis in AAV8-treated mice remain insufficient to support natural fertility.

Efficient Treatment of Pulpitis via Transplantation of Human Pluripotent Stem Cell-Derived Pericytes Partially through -Mediated T Cell Suppression.

Dental pulp pericytes are reported to have the capacity to generate odontoblasts and express multiple cytokines and chemokines that regulate the local immune microenvironment, thus participating in the repair of dental pulp injury in vivo. However, it has not yet been reported whether the transplantation of exogenous pericytes can effectively treat pulpitis, and the underlying molecular mechanism remains unknown. In this study, using a lineage-tracing mouse model, we showed that most dental pulp pericytes are derived from cranial neural crest.

Precise Correction of Lhcgr Mutation in Stem Leydig Cells by Prime Editing Rescues Hereditary Primary Hypogonadism in Mice.

Hereditary primary hypogonadism (HPH), caused by gene mutation related to testosterone synthesis in Leydig cells, usually impairs male sexual development and spermatogenesis. Genetically corrected stem Leydig cells (SLCs) transplantation may provide a new approach for treating HPH. Here, a novel nonsense-point-mutation mouse model (Lhcgr ) is first generated based on a gene mutation relative to HPH patients.

Maternal melatonin supplementation shapes gut microbiota and protects against inflammation in early life.

Background: Gut microbiota colonization is critical for immune education and nutrient metabolism. Research shows that melatonin has beneficial effects as a therapy for many diseases via modulating gut dysbiosis. However, it is unclear whether melatonin alters gut microbiota colonization in early life.

Migration deficits of the neural crest caused by CXADR triplication in a human Down syndrome stem cell model.

Down syndrome (DS) is the most common chromosomal abnormality in live-born infants and is caused by trisomy of chromosome 21. Most individuals with DS display craniofacial dysmorphology, including reduced sizes of the skull, maxilla, and mandible. However, the underlying pathogenesis remains largely unknown.

BMAL1 moonlighting as a gatekeeper for LINE1 repression and cellular senescence in primates.

Aging in humans is intricately linked with alterations in circadian rhythms concomitant with physiological decline and stem cell exhaustion. However, whether the circadian machinery directly regulates stem cell aging, especially in primates, remains poorly understood. In this study, we found that deficiency of BMAL1, the only non-redundant circadian clock component, results in an accelerated aging phenotype in both human and cynomolgus monkey mesenchymal progenitor cells (MPCs).

Autologous transplantation of thecal stem cells restores ovarian function in nonhuman primates.

Premature ovarian insufficiency (POI) is defined as the loss of ovarian activity under the age of 40. Theca cells (TCs) play a vital role during folliculogenesis and TCs dysfunction participate in the pathogenesis of POI. Therefore, transplantation of thecal stem cells (TSCs), which are capable of self-renewal and differentiation into mature TCs, may provide a new strategy for treating POI.

Single-cell analysis of nonhuman primate preimplantation development in comparison to humans and mice.

Background: Genetic programs underlying preimplantation development and early lineage segregation are highly conserved across mammals. It has been suggested that nonhuman primates would be better model organisms for human embryogenesis, but a limited number of studies have investigated the monkey preimplantation development. In this study, we collect single cells from cynomolgus monkey preimplantation embryos for transcriptome profiling and compare with single-cell RNA-seq data derived from human and mouse embryos.

Transplantation of hPSC-derived pericyte-like cells promotes functional recovery in ischemic stroke mice.

Pericytes play essential roles in blood-brain barrier (BBB) integrity and dysfunction or degeneration of pericytes is implicated in a set of neurological disorders although the underlying mechanism remains largely unknown. However, the scarcity of material sources hinders the application of BBB models in vitro for pathophysiological studies. Additionally, whether pericytes can be used to treat neurological disorders remains to be elucidated.

Transplantation of encapsulated human Leydig-like cells: A novel option for the treatment of testosterone deficiency.

Previous studies have demonstrated that the transplantation of alginate-poly-ʟ-lysine-alginate (APA)-encapsulated rat Leydig cells (LCs) provides a promising approach for treating testosterone deficiency (TD). Nevertheless, LCs have a limited capacity to proliferate, limiting the efficacy of LC transplantation therapy. Here, we established an efficient differentiation system to obtain functional Leydig-like cells (LLCs) from human stem Leydig cells (hSLCs).

Endosialin defines human stem Leydig cells with regenerative potential.

Study Question: Is endosialin a specific marker of human stem Leydig cells (SLCs) with the ability to differentiate into testosterone-producing Leydig cells (LCs) in vitro and in vivo?

Summary Answer: Endosialin is a specific marker of human SLCs which differentiate into testosterone-producing LCs in vitro and in vivo.

What Is Known Already: Human SLCs have been identified and isolated using the marker platelet-derived growth factor receptor α (PDGFRα) or nerve growth factor receptor (NGFR). However, the specificity was not high; thus, LCs and germ cells could be mistakenly sorted as SLCs if PDGFRα or NGFR was used as a marker for human SLCs isolation.

Restorative functions of Autologous Stem Leydig Cell transplantation in a Testosterone-deficient non-human primate model.

Stem Leydig cells (SLCs) transplantation can restore testosterone production in rodent models and is thus a potential solution for treating testosterone deficiency (TD). However, it remains unknown whether these favorable effects will be reproduced in more clinically relevant large-animal models. Therefore, we assessed the feasibility, safety and efficacy of autologous SLCs transplantation in a testosterone-deficient non-human primate (NHP) model.

Nestin regulates cellular redox homeostasis in lung cancer through the Keap1-Nrf2 feedback loop.

Abnormal cancer antioxidant capacity is considered as a potential mechanism of tumor malignancy. Modulation of oxidative stress status is emerging as an anti-cancer treatment. Our previous studies have found that Nestin-knockdown cells were more sensitive to oxidative stress in non-small cell lung cancer (NSCLC).

Atypical behaviour and connectivity in SHANK3-mutant macaques.

Mutation or disruption of the SH3 and ankyrin repeat domains 3 (SHANK3) gene represents a highly penetrant, monogenic risk factor for autism spectrum disorder, and is a cause of Phelan-McDermid syndrome. Recent advances in gene editing have enabled the creation of genetically engineered non-human-primate models, which might better approximate the behavioural and neural phenotypes of autism spectrum disorder than do rodent models, and may lead to more effective treatments. Here we report CRISPR-Cas9-mediated generation of germline-transmissible mutations of SHANK3 in cynomolgus macaques (Macaca fascicularis) and their F1 offspring.

Characterization and Therapeutic Application of Mesenchymal Stem Cells with Neuromesodermal Origin from Human Pluripotent Stem Cells.

Mesenchymal stem cells (MSC) hold great promise in the treatment of various diseases including autoimmune diseases, inflammatory diseases, etc., due to their pleiotropic properties. However, largely incongruent data were obtained from different MSC-based clinical trials, which may be partially due to functional heterogeneity among MSC.

Nuclear Nestin deficiency drives tumor senescence via lamin A/C-dependent nuclear deformation.

Emerging evidence has revealed that Nestin not only serves as a biomarker for multipotent stem cells, but also regulates cell proliferation and invasion in various tumors. However, the mechanistic contributions of Nestin to cancer pathogenesis are still unknown. In the present study, previously thought to reside exclusively in the cytoplasm, Nestin can also be found in the nucleus and participate in protecting tumor cells against cellular senescence.

Cell adhesion-mediated mitochondria transfer contributes to mesenchymal stem cell-induced chemoresistance on T cell acute lymphoblastic leukemia cells.

Background: Despite the high cure rate of T cell acute lymphoblastic leukemia (T-ALL), drug resistance to chemotherapy remains a significant clinical problem. Bone marrow mesenchymal stem cells (MSCs) protect leukemic cells from chemotherapy, but the underlying mechanisms are poorly understood. In this study, we aimed to uncover the mechanism of MSC-induced chemoresistance in T-ALL cells, thus providing a promising clinical therapy target.

A Nestin-Cyclin-Dependent Kinase 5-Dynamin-Related Protein 1 Axis Regulates Neural Stem/Progenitor Cell Stemness via a Metabolic Shift.

Neural stem/progenitor cells (NSPCs) transplantation provides an alternative approach for various central nervous system (CNS) diseases treatment, while the difficulties in NSPC acquisition and expansion limit their further application. Unveiling the mechanism of NSPC stemness regulation may contribute to its further application. Nestin, generally recognized as a marker of NSPCs, plays a crucial role in the CNS development and NSPC stemness maintenance.

Modeling the Pathogenesis of Charcot-Marie-Tooth Disease Type 1A Using Patient-Specific iPSCs.

Charcot-Marie-Tooth disease type 1A (CMT1A), one of the most frequent inherited peripheral neuropathies, is associated with PMP22 gene duplication. Previous studies of CMT1A mainly relied on rodent models, and it is not yet clear how PMP22 overexpression leads to the phenotype in patients. Here, we generated the human induced pluripotent stem cell (hiPSC) lines from two CMT1A patients as an in vitro cell model.

The similarities between smDCs and regDCs in alleviating the immune injury caused by transplantation of hepatocytes differentiated from ESCs.

Background: This study aimed to investigate the tolerogenic mechanisms induced by semimature dendritic cells (smDCs) and regulatory dendritic cells (regDCs) after transplantation of hepatocytes differentiated from mouse embryonic stem cells (ESCs) and to confirm the low immunogenicity of hepatocytes differentiated from ESCs.

Methods: Green fluorescent protein-labeled ESCs collected from 129 mice were cultured to differentiate into hepatocytes. smDCs and regDCs were cultured in vitro.