Patient-derived induced pluripotent stem cells (iPSCs) provide a renewable model for studying acute myeloid leukemia (AML), but whether AML-iPSCs faithfully preserve the functional heterogeneity of genetically distinct AML clones remains unclear. Here, we functionally characterized a genetically defined AML-iPSC resource comprising 34 AML-iPSC lines from 11 AML patients, with complementary assays performed across partially overlapping subsets of lines. AML-iPSC lines were classified as aberration-positive (Ab + ) or aberration-negative (Ab − ) based on retention of the clinically defining patient-specific leukemia-associated genetic abnormalities. Representative Ab + and Ab − AML-iPSC lines derived from donor hematopoietic cells exhibited comparable differentiation capacity across nonhematopoietic lineages, whereas Ab + AML-iPSC lines demonstrated reduced hematopoietic differentiation, as determined by phenotypic analysis and functional colony-forming assays. Across overlapping subsets of AML-iPSC lines, these clone-specific hematopoietic phenotypes were conserved across four independent differentiation platforms, supporting that they reflect stable clone-specific properties rather than methodological artifacts. Residual hematopoietic progenitors derived from Ab + AML-iPSC lines retained leukemic features, including persistence of leukemia-associated genetic abnormalities, immature blast-like morphology, and enhanced serial replating capacity indicative of self-renewal-associated properties. In a representative paired patient model, these progenitors also demonstrated persistent myeloid-skewed hematopoietic output following xenotransplantation. Together, these findings establish a renewable platform for mechanistic studies investigating how clonal heterogeneity contributes to disease evolution and therapeutic resistance in AML following pluripotent reprogramming.
Bone marrow-derived leptin receptor-expressing (LepR + ) stromal cells (LepR + BMSCs) have been identified as the primary source of osteoblasts, adipocytes, and fibroblasts in the bone marrow, and they play key roles in the maintenance of the bone marrow microenvironment; however, research on the fate and immunomodulatory changes of human LepR + BMSCs is limited. Here, we isolated LepR + BMSCs from a young donor and studied their fate changes of osteogenic, adipogenic, myogenic differentiation, and immunomodulation with or without CXM102, a novel compound that we have previously demonstrated its anti-osteoporotic effects in mice. Our results showed that CXM102 facilitated a preferential lineage shift toward osteogenesis from adipogenesis of LepR + BMSCs in vitro , as evidenced by increased RUNX 2 expression and decreased PPARγ in a bivalent differentiation system. Moreover, interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were markedly downregulated in HS-5 stromal cells cocultured with conditioned medium from CXM102-treated LepR + BMSCs. Furthermore, CXM102 also inhibited collagen I deposition in LepR + BMSCs when induced into myogenesis. These results demonstrated that CXM102 could promote osteogenesis, but inhibit adipogenesis and myogenesis of LepR + BMSCs, while also showing benign immunomodulation in vitro .
Stem cell-associated microRNAs (miRNAs) have emerged as pivotal regulators of osteogenesis, influencing lineage commitment, differentiation, and skeletal tissue homeostasis. Their dysregulation has been increasingly linked to a spectrum of osteogenic disorders, including osteoporosis, osteoarthritis, and impaired fracture healing. This narrative review synthesizes current evidence on the diagnostic potential of stem cell-associated miRNAs in bone-related pathologies. We highlight their roles in modulating osteoblast and osteoclast activity, maintaining mesenchymal stem cell fate, and orchestrating signaling pathways such as Wnt/β-catenin, bone morphogenetic protein, and Notch. Particular emphasis is placed on circulating miRNAs as minimally invasive biomarkers, offering prospects for early detection, disease stratification, and monitoring therapeutic response. Furthermore, we discuss methodological advances in miRNA profiling, challenges in clinical translation, and the need for standardized validation frameworks. By integrating molecular insights with translational perspectives, this review underscores the promise of stem cell-associated miRNAs as diagnostic tools in osteogenic disorders, while identifying critical gaps that must be addressed to enable their incorporation into precision medicine strategies.
Hematopoietic stem cell (HSC) has self-renewal and multilineage differentiation capacities. They sustain lifelong homeostasis and repair of damaged tissues, serving as the core cellular foundation for long-term homeostasis and regenerative repair. Maintaining HSC stemness is essential for normal hematopoiesis; this is not a static property but a dynamically regulated process that directly governs the stable operation of regular hematopoiesis. Recent studies show that HSC quiescence, self-renewal, and lineage differentiation are coordinately controlled by multiple signaling cues. Transcription factor networks, the extracellular matrix, metabolic reprogramming, and epigenetic modifications interact to form a regulatory network that governs stemness maintenance. Under physiological conditions, these factors establish stemness homeostasis; when aberrantly remodeled, they drive diseases such as leukemia and bone marrow failure. This review summarizes the factors that modulate HSC function and stemness during genetic information transmission, and discusses their biological significance. It further elaborates on the regulatory network, compares its distinct patterns in physiological versus pathological states, and explores its translational clinical value. Ultimately, this work aims to provide basic researchers with an integrated conceptual framework and to offer feasible forward-looking strategies for clinical translation.
Dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), and extracellular vesicles (EVs) show regenerative potential, but clinical translation depends on a reproducible product–process–procedure system. This systematic scoping review mapped how DPSC- and EV-containing dental products are defined, manufactured, formulated, dosed, delivered, monitored, and regulated. Following Joanna Briggs Institute guidance (JBI) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR), an umbrella-assisted strategy combined two recent high-coverage reviews with a targeted update through July 15, 2026. Data were charted for source, characterization, carrier, dose, delivery, visualization, safety, outcomes, and manufacturing readiness; a nine-domain review-level framework (Translational Readiness Appraisal for Dental cell and EV products) summarized relative maturity without serving as a validated clinical score. The map comprised 52 unique primary reports and nine methodological or secondary sources. Scaffold-based DPSC/SHED studies generally favored cell-containing constructs, but most were heterogeneous short-term animal experiments. Small human studies of autologous DPSC or SHED products reported encouraging feasibility and few serious safety signals, yet were underpowered for effectiveness or uncommon harms. Dental EV evidence remained predominantly preclinical; isolation, particle-normalized dosing, potency, storage, biodistribution, and batch comparability were frequently incomplete. Magnification was not consistently standardized as a delivery variable. Relative readiness was highest for autologous DPSC pulp products, intermediate for DPSC-scaffold bone or periodontal products, and low for dental EV products. Translation now requires indication-specific potency assays, carrier-product codevelopment, dose–response and biodistribution studies, documented delivery fidelity, standardized outcomes, long-term safety follow-up, and explicit good manufacturing practice (GMP) and regulatory strategies before confirmatory trials.
