Stem Cell Res Ther [JOURNAL]
Sun
200 papers
HAMA microneedles patch loaded with Three-Dimensional exosome and Mupirocin promote diabetic wound healing.
Hu Y, Wu Y, Luo Y … +7 more , Kong X, Zhu D, Wang K, Lan X, Zhu L, Xu T, Wang K
Stem Cell Res Ther · 2026 May · PMID 42169069 · Full text
Diabetic wound healing impairment poses significant clinical challenges due to infection risks, poor angiogenesis, and chronic inflammation, often leading to amputation or death. Recently, mesenchymal stem cell-derived e...
Diabetic wound healing impairment poses significant clinical challenges due to infection risks, poor angiogenesis, and chronic inflammation, often leading to amputation or death. Recently, mesenchymal stem cell-derived exosomes (Exos) exhibit potential in enhancing angiogenesis and suppressing inflammation, yet clinical application is limited by short half-life, low bioavailability, and high costs. Three-dimensional (3D) culture technology improves exosome yield and therapeutic efficacy, demonstrating superior performance in tissue regeneration. Concurrently, microneedle (MN) systems enable efficient transdermal drug delivery with minimal invasiveness. This study integrates 3d-Exo with Mupirocin into a hyaluronic acid methacrylate (HAMA)-based MN patch (3d-Exo MN) to enhance diabetic wound healing. The HAMA matrix ensures exosome stability and controlled release, while Mupirocin targets infection. In vitro and in vivo evaluations reveal that 3d-Exo MN significantly promotes cell proliferation, migration, and neovascularization, addressing key limitations of conventional therapies. By synergizing 3d-Exo advantages with MN-mediated delivery, this innovative platform offers a targeted, biocompatible strategy for diabetic wound management, bridging gaps in current treatment paradigms through enhanced drug efficacy and localized action.
Dental pulp stem cell exosomes promote angiogenesis via the PI3K/Akt signaling pathway to treat androgenetic alopecia.
Luo W, Shen Y, Yu W … +6 more , Zhao L, Wu M, Xu L, Liu Z, Yang L, Zhang X
Stem Cell Res Ther · 2026 May · PMID 42169044 · Full text
BACKGROUND: Androgenetic alopecia (AGA), the most common form of hair loss, is currently treated with pharmacological agents that often yield inconsistent results and side effects, highlighting the need for novel therape...
BACKGROUND: Androgenetic alopecia (AGA), the most common form of hair loss, is currently treated with pharmacological agents that often yield inconsistent results and side effects, highlighting the need for novel therapeutic approaches. This study aimed to investigate the therapeutic potential and molecular mechanisms of exosomes derived from dental pulp mesenchymal stem cells (DPSC-Exos) for AGA. METHODS: We employed a dihydrotestosterone (DHT)-induced AGA mouse model and treated groups with DPSC-Exos or minoxidil. Hair growth was assessed macroscopically and histologically. In vitro, human dermal papilla cells (DPCs) were treated with DHT and/or DPSC-Exos, with or without the PI3K inhibitor LY294002. Analyses included RNA sequencing, RT-qPCR, western blotting, immunofluorescence, and functional assays (proliferation, migration). Statistical significance was determined using Student's t-test or one-way ANOVA with appropriate post-hoc tests. RESULTS: DPSC-Exos significantly promoted hair regrowth, increased hair follicle density, and enhanced dermal thickness in mice, with efficacy comparable to minoxidil. Transcriptomic and protein analysis revealed DPSC-Exos activated the PI3K/Akt pathway and upregulated VEGFA, leading to perifollicular vascular network reconstruction. In vitro, DPSC-Exos rescued DHT-induced suppression of DPC proliferation, migration, and expression of hair-inductive markers (ALP, α-SMA). These effects were mediated through upregulation of pro-angiogenic factors (VEGFA, FGF2, ANGPT1) and were completely abolished by PI3K inhibition, confirming the pathway's necessity. A positive feedback loop between PI3K/Akt activation and VEGFA expression was identified. CONCLUSION: Our findings demonstrate that DPSC-Exos promote hair regeneration by activating the PI3K/Akt-VEGFA axis, thereby restoring the follicular vascular niche and DPC function. This study positions DPSC-Exos as a promising, cell-free therapeutic strategy for AGA, with clear mechanistic foundations for future translational development.
Targeting skin barrier repair: mechanisms of action, therapeutic evidence, and clinical translation challenges of mesenchymal stem cell-derived exosomes.
Li Y, Huang J, Fu Z … +5 more , Gao L, Tong X, Zhou L, Zeng J, Tan L
Stem Cell Res Ther · 2026 May · PMID 42163388 · Full text
Dysfunction of the skin barrier is a central pathological feature in dermatology, driving the need for innovative repair strategies. Mesenchymal stem cell-derived exosomes (MSC-exos) represent a promising cell-free thera...
Dysfunction of the skin barrier is a central pathological feature in dermatology, driving the need for innovative repair strategies. Mesenchymal stem cell-derived exosomes (MSC-exos) represent a promising cell-free therapeutic paradigm, leveraging their innate cargo to modulate regeneration and immune responses. This review systematically examines the multifaceted role of MSC-exos in restoring skin barrier integrity. We delineate their molecular mechanisms in repairing physical, immunological, and microbial barrier components, supported by evidence from preclinical disease models. The influence of MSC source and preconditioning on exosome efficacy is analyzed, alongside emerging bioengineering approaches. Crucially, we identify and discuss the key translational challenges-including standardization, scalable manufacturing, and regulatory pathways-that must be addressed to advance these nanotherapeutics toward clinical application. This synthesis provides a critical framework for future research aimed at harnessing MSC-exos for targeted barrier repair.
Prevascularization of electrospun PCL/PLA scaffolds using human adipose-derived stem and endothelial cells enhances vascular integration and host angiogenesis in vivo.
Grob L, Brislinger D, Mueller M … +9 more , Högler A, Galistl K, Sundl M, Kummer D, Ghaffari-Tabrizi-Wizsy N, Müller H, Pichlsberger M, Kamolz LP, Lang-Olip I
Stem Cell Res Ther · 2026 May · PMID 42163377 · Full text
BACKGROUND: Inadequate vascularization remains a major limitation in tissue engineering, often leading to graft failure due to limited oxygen and nutrient supply. Prevascularization, the formation of microvascular networ...
BACKGROUND: Inadequate vascularization remains a major limitation in tissue engineering, often leading to graft failure due to limited oxygen and nutrient supply. Prevascularization, the formation of microvascular networks within scaffolds before implantation, aims to accelerate perfusion and improve graft integration. We developed bilayer electrospun poly(ε-caprolactone)/poly(l-lactide) (PCL/PLA) scaffolds prevascularized by co-culture of human adipose-derived mesenchymal stem cells (AD-MSCs) and human placental arterial endothelial cells (HPAECs). METHODS: AD-MSCs were isolated from lipoaspirates and characterized by flow cytometry and functional assays. Bilayered PCL/PLA scaffolds were engineered with a wide-meshed layer for cell infiltration and a fine-meshed layer for mechanical stability. Scaffolds were seeded with AD-MSCs, HPAECs, or both (co-culture). Cell viability, adhesion, and apoptosis were analyzed histologically. Angiogenic and vasculogenic potential was evaluated in vitro and in vivo using the chick chorioallantoic membrane (CAM) assay. RESULTS: AD-MSCs expressed characteristic markers, demonstrated adipogenic and osteogenic differentiation, and promoted angiogenesis in 2D co-culture. ELISA analyses indicated dynamic secretion of VEGF, HGF, and bFGF, reflecting both paracrine and contact-dependent AD-MSC-HPAEC interactions. On scaffolds, cells primarily adhered to the wide-meshed layer. Co-culture induced vessel-like structures within a multicellular stromal environment; monocultures did not support prevascularization. Five days post-implantation, prevascularized scaffolds exhibited human microvessels at the scaffold-CAM interface and in adjacent tissue, closely associated with AD-MSCs and containing chicken erythrocytes-indicating successful anastomosis and functional perfusion. Quantitative analysis showed a significant increase in vessel branching points in the host CAM tissue in response to AD-MSC-only (2.8-fold) and co-culture (3.5-fold) scaffolds versus acellular controls (p < 0.05). HPAEC-only scaffolds did not promote vascular outgrowth, likely due to poor cell survival. CONCLUSION: Scaffolds seeded with AD-MSCs enhanced host angiogenesis, while only co-cultures with HPAECs supported scaffold prevascularization and functional vascular integration in vivo. The stromal-endothelial combination enabled formation of perfused human microvessels and promoted host vascular remodeling. These findings underscore the translational potential of prevascularized, electrospun scaffolds for improving graft survival in ischemic or poorly vascularized environments.
Adipose tissue-derived mesenchymal stem cells combined with prednisone synergistically ameliorate autoimmune hepatitis in mice.
Kong J, Liang X, Chen G … +3 more , Liu X, Liao N, Li D
Stem Cell Res Ther · 2026 May · PMID 42163288 · Full text
BACKGROUND: The combination of adipose tissue-derived mesenchymal stem cell (ADSC) transplantation with conventional therapy for autoimmune hepatitis (AIH) represents a critical step toward the clinical translation of AD...
BACKGROUND: The combination of adipose tissue-derived mesenchymal stem cell (ADSC) transplantation with conventional therapy for autoimmune hepatitis (AIH) represents a critical step toward the clinical translation of ADSC-based therapeutics. However, no preclinical studies have yet reported on such combination therapy for AIH. This study aims to evaluate the therapeutic efficacy of ADSC-prednisone (AP) combined therapy in an AIH mouse model and to investigate the underlying mechanisms. METHODS: ConA-induced and CFA/S100-induced AIH mice were treated with prednisone, ADSCs, or AP combination therapy. Serum biochemistry, histopathology, immune cell infiltration, cytokine profiles, MAPK signaling pathways (p38/MAPK, JNK/ERK), and single-cell RNA sequencing (scRNA-seq) were analyzed. RESULTS: Both ADSC and prednisone monotherapies significantly reduced serum transaminases (ALT, AST, ALP, TBIL) and hepatic inflammation compared with untreated controls. Notably, AP combination therapy demonstrated superior protection, with greater reductions in immune cell infiltration (CD4⁺, CD8⁺, CD11b⁺), pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-12), and autoantibody production (IgG). Mechanistically, ADSCs suppressed p38/MAPK activation, while AP further enhanced inhibition of JNK/p38 signaling. scRNA-seq revealed that AP therapy reshaped the liver cellular landscape, reduced immune cell abundance, and promoted regenerative signaling networks involving VEGF, TGF-β, and FGF pathways. CONCLUSION: ADSCs combined with prednisone synergistically ameliorate immune-mediated liver injury through dual immunosuppression and modulation of key signaling pathways, promoting immune tolerance and tissue repair. This strategy offers a promising therapeutic approach for AIH.
Variable cMyBP-C expression from cell to cell in a MYBPC3 hiPSC-CM model recapitulates HCM patient phenotype.
Ivaskevica K, Kowalski K, Piep B … +8 more , Teske J, Meissner JD, Kosanke M, Radocaj A, Montag J, Zweigerdt R, Kraft T, Konze SA
Stem Cell Res Ther · 2026 May · PMID 42152135 · Full text
BACKGROUND: Hypertrophic cardiomyopathy (HCM) is frequently associated with mutations in cardiac myosin binding protein C (cMyBP-C; MYBPC3) and cMyBP-C haploinsufficiency. Previously we discovered burst-like transcriptio...
BACKGROUND: Hypertrophic cardiomyopathy (HCM) is frequently associated with mutations in cardiac myosin binding protein C (cMyBP-C; MYBPC3) and cMyBP-C haploinsufficiency. Previously we discovered burst-like transcription of MYBPC3 and unequal amounts of wild type cMyBP-C from cardiomyocyte to cardiomyocyte in HCM-patient's myocardium. The present study introduces human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) carrying the patient-specific heterozygous MYBPC3 c.927-2 A > G mutation and the respective isogenic control to examine in long-term culture whether comparable pathophysiological features exist in vitro. METHODS: We generated a human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) model harboring the patient-specific MYBPC3 c.927-2 A > G splice-site mutation. An isogenic control line was used for direct comparison. We assessed cMyBP-C protein expression, transcriptional dynamics, contractile function, and calcium handling, and compared the cellular phenotype to heart tissue from the HCM patient with the same mutation. RESULTS: cMyBP-C haploinsufficiency in MYBPC3-hiPSC-CMs was confirmed by Western blot. Immunostaining showed myofibrillar disarray and an increasing proportion of cMyBP-C-negative CMs over time for mutant hiPSC-CMs, closely mirrored the variable cMyBP-C protein expression observed in HCM-patient's myocardium. RNA-FISH revealed variable MYBPC3 transcription from cell to cell, likely contributing to cMyBP-C expression heterogeneity. Twitch shortening velocity slowed over time while Ca²⁺ transient kinetics accelerated in mutant hiPSC-CMs. Transcriptomic analysis revealed dysregulation of pathways associated with contraction, calcium handling, and HCM. CONCLUSIONS: This study presents a validated hiPSC-based model of MYBPC3-associated HCM that captures the variability in protein expression and functional phenotype observed in patient heart tissue. Our findings support the relevance of single-cell transcriptional variability in HCM pathogenesis and highlight the utility of this model for future studies.
Cadherin 19 deficiency inhibits osteogenic differentiation and bone formation by regulating PI3K/AKT signaling pathway.
Zhou H, Cheng Y, Chen L … +7 more , Zhang Y, Xiao H, Zhou C, Fu H, Zhang X, Xu L, Xu D
Stem Cell Res Ther · 2026 May · PMID 42152129 · Full text
BACKGROUND: Osteoporosis (OP) is a systemic bone disease characterized by damage to bone strength, leading to increased bone fragility and fracture risk. Cadherin 19 (CDH19) is located on chromosomes 18q22-q23, and 18q d...
BACKGROUND: Osteoporosis (OP) is a systemic bone disease characterized by damage to bone strength, leading to increased bone fragility and fracture risk. Cadherin 19 (CDH19) is located on chromosomes 18q22-q23, and 18q deletion is associated with terminal deletion diseases, including foot/hand deformities. However, the role of CDH19 in bone remains undefined. METHODS: A conditional knockout mouse model of the CDH19 gene was constructed using the Cre-loxP system, and the bone mass and bone morphology in mice were investigated using microCT and histological staining. Osteoblasts were isolated and cultured from wild-type and CDH19 knockout mice. Cell proliferation and differentiation were explored through EdU labeling, qPCR, alkaline phosphatase (ALP)/ alizarin red S (ARS) staining, and Western blot assays. The expression of genes altered in CDH19 gene knockout osteoblast was checked by RNA sequencing (RNA-seq), and subsequently confirmed by immunofluorescence and Western blot. RESULTS: We found that CDH19 could maintain the normal proliferation and differentiation in osteoblasts. After knocking out the CDH19 gene, the abilities of proliferation and osteogenesis were significantly inhibited in osteoblasts. Moreover, the bone mass of CDH19 knockout mice was significantly reduced, characterized by decreases in bone density, trabecular number, and bone volume fraction. The RNAseq analysis and western blot showed the PI3K/AKT signaling pathway was significantly inhibited in osteoblasts with CDH19 deletion. Furthermore, we demonstrated that administration of PI3K/AKT signaling pathway agonist 740Y-P partially alleviated the inhibition of osteogenic differentiation caused by CDH19 deletion in vitro and in vivo. CONCLUSION: This study demonstrated that CDH19 regulated osteogenic differentiation by modulating the PI3K/AKT signaling pathway in osteoblasts. CDH19 may become a novel target for the treatment of bone diseases.
hAECs restore follicular development in premature ovarian insufficiency via IGFBP2/IGF1R-mediated intercellular communication.
Cao W, Shen L, Zhang Q … +6 more , Huang Y, Sun J, Cheng Z, Xu J, Zhang Q, Lai D
Stem Cell Res Ther · 2026 May · PMID 42144654 · Full text
BACKGROUND: Premature ovarian insufficiency (POI) is defined by ovarian dysfunction and consequent decreased fertility. While follicular depletion is an acknowledged factor, dynamic changes in follicular subpopulations a...
BACKGROUND: Premature ovarian insufficiency (POI) is defined by ovarian dysfunction and consequent decreased fertility. While follicular depletion is an acknowledged factor, dynamic changes in follicular subpopulations and single-cell-level niche remodeling remains largely unexplored. Human amniotic epithelial cells (hAECs) represent a promising regenerative approach for restoring ovarian function; however, the underlying mechanism in promoting follicular development remains unclear. METHODS: We established a chemotherapy-induced POI mouse model and conducted single-nucleus RNA sequencing (snRNA-seq) to systematically characterize ovarian cellular heterogeneity, residual follicular development, and ovarian microenvironmental alteration. A human-derived cell projection model was established to track the distribution of transplanted hAECs. Furthermore, the functional role of IGF1R signaling in granulosa cells was validated using both in vitro culture assays and in vivo interventions. RESULTS: We identified eight distinct ovarian cell types and uncovered stage-specific injury patterns: acute chemotherapy exposure induced massive loss of granulosa cells and oocytes, while the chronic phase was characterized by fibrotic accumulation and immune infiltration. Furthermore, residual follicles exhibited aberrant development trajectories and compromised progression, primarily due to disrupted granulosa cells -oocytes communication. Notably, hAEC transplantation significantly enhanced follicle survival, partially attenuated fibrosis and promoted ovarian structural restoration. Mechanistically, hAECs-derived IGFBP2 regulated IGF1R expression in granulosa cells, thereby reactivating the Akt/FoxO3A signaling pathway and downregulating the senescence marker P21. CONCLUSIONS: This study presents a time-resolved snRNA-seq atlas capturing both acute and chronic injury phases in a chemotherapy-induced POI model, combined with a human-mouse projection approach to track transplanted hAECs in damaged ovaries. Our study establishes a novel cell-based therapeutic strategy for partial ovarian functional recovery, in which hAEC-derived IGFBP2 restores granulosa cell function and intercellular communication by regulating the IGF1R/Akt/mTOR signaling axis.
The cellular ecosystem of skeletal muscle regeneration: molecular mechanisms, pathological disorders, and potential therapeutic strategies.
Gong J, Xu H, Yao X … +5 more , Wei Y, Li X, Shen Y, Chen B, Sun H
Stem Cell Res Ther · 2026 May · PMID 42143395 · Full text
Skeletal muscle regeneration is a highly coordinated physiological process. It relies on the intricate collaboration of a complex cellular ecosystem. This ecosystem includes muscle stem cells, immune cells, stromal cells...
Skeletal muscle regeneration is a highly coordinated physiological process. It relies on the intricate collaboration of a complex cellular ecosystem. This ecosystem includes muscle stem cells, immune cells, stromal cells, vascular cells, neural cells, and the extracellular matrix. Research has recently expanded beyond focusing solely on satellite cells. It now delves into the multi-level regulatory networks within this ecosystem. These networks encompass key signaling pathways, such as Wnt/β-catenin, TGF-β, Hippo/YAP, and AMPK. They also include epigenetic regulation, cellular metabolic reprogramming, and extracellular vesicle-mediated intercellular communication. However, under pathological conditions, this regenerative program is severely impaired. This leads to failed repair, fibrosis, and fatty infiltration, ultimately resulting in loss of muscle function. This review aims to systematically outline recent advances in the field of skeletal muscle regeneration. First, from the perspective of the "cellular ecosystem," we will elaborate on the dynamic behaviors and regulatory mechanisms of various cell types during regeneration. Second, we will dissect the core mechanisms underlying regenerative failures in various pathological states. Third, we will comprehensively evaluate the most promising current intervention strategies. Finally, considering the limitations of current research, we will provide future perspectives. This review aims to systematically integrate existing knowledge and provide a clear roadmap for future research, ultimately offering a robust theoretical foundation and innovative insights for the development of clinical treatments targeting skeletal muscle regenerative disorders.
Autologous bone marrow mesenchymal stem cell mitochondrial transplantation in recurrent assisted reproductive technology failure: a randomized controlled trial.
Liu X, Wang D, Jia L … +7 more , Chen W, Huang R, Fang C, Du C, Yang L, Liu X, Liang X
Stem Cell Res Ther · 2026 May · PMID 42129850 · Full text
BACKGROUND: Mitochondrial dysfunction contributes to poor embryo quality and recurrent assisted reproductive technology (ART) failure. Mitochondrial transplantation (MIT), which involves supplementing oocytes with exogen...
BACKGROUND: Mitochondrial dysfunction contributes to poor embryo quality and recurrent assisted reproductive technology (ART) failure. Mitochondrial transplantation (MIT), which involves supplementing oocytes with exogenous mitochondria, has been proposed as a novel strategy to improve ART outcomes. However, both its clinical efficacy and safety remain unclear. METHODS: In this single-center trial, 151 patients with a history of ≥ 2 failed ART cycles provided 1178 metaphase II (MII) oocytes. Sibling oocytes were randomized 1:1 to receive autologous bone marrow mesenchymal stem cells (BMSCs) mitochondria co-injection during intracytoplasmic sperm injection (ICSI) or standard ICSI. The primary outcome was the rate of day-3 good-quality embryos. RESULTS: MIT significantly accelerated early embryonic cleavage at the 3-cell stage and 5-cell stage, but this morphokinetic alteration did not translate into improvements in good-quality embryo rate, clinical pregnancy rate, or live birth rate. Long-term follow-up of 23 live births revealed no adverse effects, with all offspring exhibiting normal growth and development. Exploratory analysis revealed that oocytes yielding ≥ 70% transferable embryos after MIT harbored an elevated higher burden of medium frequency (0.05-0.5) mtDNA point mutations. CONCLUSIONS: While autologous BMSCs-MIT transiently alters early cleavage kinetics, it does not demonstrate a clinical advantage in unselected patients with recurrent ART failure. Nevertheless, its observed safety profile and the identification of mtDNA mutation burden as a potential predictive biomarker provide a foundation for shifting future MIT research from a universal approach toward precision application in molecularly stratified populations. Trial registration ClinicalTrials.gov registration: NCT03639506.
Emerging therapeutic potential of umbilical cord-derived extracellular vesicles in lung-injurious diseases: a review of recent advances.
Xiao S, Wang L, Li X … +4 more , Zheng Q, Zhou L, Song X, Yang J
Stem Cell Res Ther · 2026 May · PMID 42121270 · Full text
Recent research has shown that extracellular vesicles (EVs) have significant potential in treating lung injuries. These vesicles facilitate communication between cells and regulate important biological processes, includi...
Recent research has shown that extracellular vesicles (EVs) have significant potential in treating lung injuries. These vesicles facilitate communication between cells and regulate important biological processes, including cell growth, blood vessel formation, and inflammatory responses. Due to their natural ability to cross biological barriers and low risk of immune rejection, EVs are potential vehicles for targeted drug delivery. Among various biological sources, umbilical cord-derived EVs are highly advantageous because the collection process is non-invasive and provides a high yield of vesicles. Preclinical studies have demonstrated their therapeutic potential in conditions such as bronchopulmonary dysplasia, chronic obstructive pulmonary disease, acute respiratory distress syndrome, and asthma. This review summarizes the current evidence supporting the use of umbilical cord-derived EVs for lung diseases. It also discusses key translational challenges, such as manufacturing scalability and product consistency, alongside advanced engineering strategies for future clinical use.
Serial brain FDG-PET and IMZ-SPECT following intracerebral MSC transplantation in patients with subacute ischemic stroke.
Kawabori M, Hirata K, Shichinohe H … +7 more , Watanabe S, Miura A, Ito YM, Kudo K, Kuroda S, Houkin K, Fujimura M
Stem Cell Res Ther · 2026 May · PMID 42121257 · Full text
Ischemic stroke is a leading cause of mortality and long-term neurological disability worldwide, and cell-based therapies represent a promising approach. Although clinical studies have reported favorable outcomes followi...
Ischemic stroke is a leading cause of mortality and long-term neurological disability worldwide, and cell-based therapies represent a promising approach. Although clinical studies have reported favorable outcomes following cell transplantation, the effects on host neuronal integrity remain incompletely understood. This study investigated temporal and spatial changes in fluorodeoxyglucose positron emission tomography (FDG-PET) and 123I-iomazenil single-photon emission computed tomography (IMZ-SPECT) after intracerebral cell transplantation in patients with subacute ischemic stroke and examined their relationship with functional recovery. Seven adults with severe post-stroke disability underwent autologous mesenchymal stromal cell (HUNS001-01) transplantation 47-64 days after stroke onset. Brain FDG-PET and IMZ-SPECT were performed preoperatively and at 1, 3, and 12 months post-transplantation. Regions of interest were first manually set in the ipsilateral cortex where the 12-month postoperative-to-preoperative standard uptake value ratio seems increased, and followed by quantitative measurement. Five of seven patients demonstrated 5% or more increase of FDG-PET and/or IMZ-SPECT uptake in peri-infarct cortical regions, predominantly within the frontal or temporal cortex. Transplanted cells localized either within metabolically enhanced regions or in anatomically remote areas. FDG-PET and IMZ-SPECT changes were strongly interacted in each other and were associated with functional improvement. Overall, improvement of glucose metabolism and synaptic density/viability were observed in patient with subacute ischemic stroke, which may have been attributable to cell transplantation.Trial registration: UMIN000026130.
Mechanomedicine-guided mechanical preconditioning of dental-derived stromal cells for tissue regeneration.
Pan X, Yang L, Zou J … +8 more , Xu G, Jiang Y, Liu G, Wang Y, Wang X, Liu H, Ren Y, Shi Q
Stem Cell Res Ther · 2026 May · PMID 42116103 · Full text
Dental-derived stromal cells (DSCs), including periodontal ligament stem cells, dental pulp stem cells, stem cells from the apical papilla, and stem cells from human exfoliated deciduous teeth, are promising candidates f...
Dental-derived stromal cells (DSCs), including periodontal ligament stem cells, dental pulp stem cells, stem cells from the apical papilla, and stem cells from human exfoliated deciduous teeth, are promising candidates for oral and craniofacial regeneration because of their accessibility, expandability, and functional relevance to periodontal, dentin-pulp, bone, and neurovascular repair. However, the therapeutic performance of DSC-based products remains inconsistent, partly because conventionally expanded cells may be insufficiently adapted to the mechanical cues encountered in vivo. In this Review, we present mechanical preconditioning as a mechanomedicine-guided strategy for ex vivo functional priming of DSCs. We summarize how major DSC populations respond to defined biophysical cues such as tensile and compressive forces, fluid shear stress, hydrostatic pressure, matrix stiffness, and surface topography, and we discuss the principal mechanotransduction pathways involved. We further outline representative quantitative loading windows and consider how these may support subtype-specific and indication-specific preconditioning design. Finally, we highlight key translational barriers, including stromal cell heterogeneity, donor variability, senescence, uncertain persistence of mechanically induced states, safety concerns, and the lack of standardized manufacturing workflows. Overall, clinical translation will require a shift from descriptive mechanobiology toward parameter-defined, indication-specific, and good manufacturing practice-compatible preconditioning strategies for DSC-based regeneration.
Induced pluripotent stem cell-based modeling of hemolytic anemia in patients with compound heterozygous KLF1 mutations reveals defective erythroid differentiation.
Pratumkaew P, Wattanapanitch M, Viprakasit V … +2 more , Kheolamai P, Issaragrisil S
Stem Cell Res Ther · 2026 May · PMID 42108505 · Full text
BACKGROUND: Transfusion-dependent hemolytic anemia caused by compound heterozygosity due to mutations in the erythroid Krüppel-like factor 1 (KLF1) gene is a rare and severe blood disorder. The clinical manifestations of...
BACKGROUND: Transfusion-dependent hemolytic anemia caused by compound heterozygosity due to mutations in the erythroid Krüppel-like factor 1 (KLF1) gene is a rare and severe blood disorder. The clinical manifestations of the patient are mainly related to erythroid cells. Moreover, the roles of the identified KLF1 mutations in the pathophysiology of this disease remain unclear due to the lack of an appropriate study model. The advent of genome editing technology combined with the generation of patient-specific induced pluripotent stem cells (iPSCs) may provide a better understanding of the molecular mechanisms underlying this disease in an in vitro system and offer a novel therapeutic approach in the future. METHODS: KLF1-mutant iPSCs were generated from patients with compound heterozygosity of KLF1 mutations, and the mutation was corrected through the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system together with a single-stranded oligodeoxynucleotide donor template (ssODN). The obtained iPSC lines were differentiated towards erythroid cells, and the disease-related phenotypes were examined. RESULTS: Erythroid cells derived from KLF1-mutated iPSCs had lower proliferative capacity, showed delayed maturation, and expressed lower level of the KLF1-related gene, CD44. These results were consistent with some of the phenotypes observed in the patients. After CRISPR/Cas9 gene editing, the corrected iPSCs retained pluripotency, exhibited a normal karyotype, and had undetectable off-target mutations. Importantly, some of the defects were partially restored after genetic correction of the KLF1 gene. CONCLUSIONS: KLF1-iPSCs presented disease-related phenotypes of compound heterozygous KLF1 mutations, which could be mediated by gene editing through CRISPR/Cas9 and ssODN. This study offers a useful strategy for studying the underlying disease mechanisms of rare diseases, which could be applied to the development of novel treatments for inherited blood disorders in the future.
Retraction Note: Efficacy of using adipose-derived stem cells and PRP on regeneration of 40 -mm long sciatic nerve defect bridged by polyglycolic-polypropylene mesh in canine model.
Khaled MM, Ibrahium AM, Abdelgalil AI … +5 more , El-Saied MA, Yassin AM, Abouquerin N, Rizk H, El-Bably SH
Stem Cell Res Ther · 2026 May · PMID 42108491 · Full text
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Awakening endogenous repair: salidroside boosts mitophagy in NPMSCs via SIRT1/FOXO3 to combat intervertebral disc degeneration.
Li Z, Wu Y, Hua B … +11 more , Sun H, Wu H, Zai S, Liu C, Zhang Y, Li Z, You X, Huang Y, Lu X, Yin G, Zhang L
Stem Cell Res Ther · 2026 May · PMID 42106856 · Full text
BACKGROUND: Intervertebral disc degeneration (IVDD) is a major cause of low back pain, characterized by mitochondrial dysfunction and impaired mitophagy in nucleus pulposus-derived mesenchymal stem cells (NPMSCs). Sirtui...
BACKGROUND: Intervertebral disc degeneration (IVDD) is a major cause of low back pain, characterized by mitochondrial dysfunction and impaired mitophagy in nucleus pulposus-derived mesenchymal stem cells (NPMSCs). Sirtuin 1 (SIRT1), a key regulator of mitochondrial quality control, is downregulated in degenerated discs. Salidroside (Sal), a natural compound from Rhodiola rosea, has shown potential in enhancing mitophagy, but its mechanism in IVDD remains unclear. METHODS: Using network pharmacology, molecular docking, and dynamics simulations, we identified SIRT1 as a key target of Sal. Human and rat NPMSCs were isolated and treated with tert-butyl hydroperoxide (TBHP) to induce degeneration. In vitro assays included CCK-8, EdU, SA-β-Gal, JC-1, Western blot, immunofluorescence, and transmission electron microscope (TEM). An in vivo rat IVDD model was established via needle puncture and treated with Sal and/or the autophagy inhibitor 3-MA. Histological, immunohistochemical, and imaging analyses were performed to evaluate IVDD. RESULTS: Sal bound stably to SIRT1 and activated SIRT1/FOXO3 pathway, promoting mitophagic flux, reducing reactive oxygen species accumulation, and suppressing apoptosis in NPMSCs. SIRT1 knockdown or 3-MA treatment abolished Sal's protective effects. In vivo, Sal treatment preserved disc height, reduced apoptosis, and enhanced mitophagy, while 3-MA exacerbated degeneration. CONCLUSIONS: Sal attenuates IVDD by activating SIRT1/FOXO3-mediated mitophagy, restoring mitochondrial homeostasis, and reducing NPMSCs apoptosis. These results suggest that the activation of the SIRT1/FOXO3-mitophagy axis may represent a potential therapeutic strategy for mitigating IVDD.
LNGFR promoting osteogenic differentiation of ectomesenchyme stem cells via activation of GHR-JAK-STAT/IGF1 signaling pathway.
Wang K, Zeng X, Zhang Y … +7 more , Zou Y, Ye J, Zhao Y, Jin H, Zhang J, Nie X, Cheng G
Stem Cell Res Ther · 2026 May · PMID 42106838 · Full text
Ectomesenchymal stem cells (EMSCs) are critical for craniofacial bone development, and low-affinity nerve growth factor receptor (LNGFR) is closely associated with their stemness. However, the specific role of LNGFR in E...
Ectomesenchymal stem cells (EMSCs) are critical for craniofacial bone development, and low-affinity nerve growth factor receptor (LNGFR) is closely associated with their stemness. However, the specific role of LNGFR in EMSC osteogenesis remains unclear. Here, we investigated this using Lngfr knockout (lngfr) mice and demonstrated that lngfrEMSCs exhibited decreased proliferation, migration, and osteogenic differentiation capacities in vitro. Furthermore, impaired skeletal development and reduced mineralization were observed in lngfr fetal mice in vivo. Circular RNA (circRNA) sequencing identified the growth hormone (GH) pathway as a key factor involved in LNGFR-regulated osteogenesis of EMSCs. Co-immunoprecipitation (Co-IP) assays further confirmed the interaction between LNGFR and growth hormone receptor (GHR). lngfrsuppressed GHR expression and Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) phosphorylation, leading to downregulation of the GH/insulin-like growth factor 1 (IGF-1) signaling pathway. Modulation of the JAK/STAT pathway affected osteogenesis, while exogenous GH rescued the osteogenic defects via the GHR/JAK-STAT/IGF-1 axis. Collectively, these findings demonstrated that LNGFR promoted EMSC osteogenesis by activating the GHR/JAK-STAT/GH-IGF-1 signaling axis, providing new insights into craniofacial development and regenerative medicine.
Dental pulp stem cell-derived exosomes attenuate psoriatic inflammation by restoring epithelial redox homeostasis via a miR-1246/miR-17-3p-GPX2-NF-κB axis.
Wang S, Zhuang D, Hou D … +7 more , Feng T, Shen L, Shi Y, Xu Q, Guo J, Wu X, Yuan G
Stem Cell Res Ther · 2026 May · PMID 42106764 · Full text
BACKGROUND: Psoriasis is driven by sustained epidermal inflammation tightly coupled to dysregulated redox homeostasis. Although current systemic therapies are effective, their long-term use is limited by safety concerns....
BACKGROUND: Psoriasis is driven by sustained epidermal inflammation tightly coupled to dysregulated redox homeostasis. Although current systemic therapies are effective, their long-term use is limited by safety concerns. Dental pulp stem cell-derived exosomes (DPSC-Exo) have emerged as promising immunomodulatory, cell-free therapeutics, yet their role in regulating epithelial redox-inflammatory balance remains undefined. METHODS: The therapeutic effects of DPSC-Exo were evaluated using an imiquimod-induced mouse model of psoriasis, ex vivo human skin explants, and M5-stimulated primary human keratinocytes. Transcriptomic profiling, immunostaining, and gain- and loss-of-function analyses were performed to define the underlying molecular mechanisms. RESULTS: Topical administration of DPSC-Exo markedly reduced epidermal hyperplasia, neutrophil infiltration, angiogenesis, and expression of key psoriatic mediators, including IL-23 A, IL-17 A, and antimicrobial peptides. These effects were consistently reproduced in human skin explants and keratinocyte models. RNA-sequencing identified glutathione peroxidase 2 (GPX2), a key epithelial antioxidant enzyme, as a prominently upregulated target following DPSC-Exo treatment. Restoration of GPX2 suppressed NF-κB activation and downstream cytokine production, whereas GPX2 silencing abolished the protective effects of DPSC-Exo. Mechanistically, two exosomal microRNAs, miR-1246 and miR-17-3p, were required for GPX2 induction and mediated the majority of the observed anti-inflammatory responses. CONCLUSIONS: These findings identify a previously unrecognized miRNA-GPX2-NF-κB axis through which DPSC-Exo restore epithelial redox-inflammatory homeostasis. Our study supports DPSC-Exo as a promising cell-free therapeutic candidate for psoriasis and highlights epithelial redox regulation as a potentially targetable mechanism for inflammatory skin diseases.
Mesenchymal stromal cells therapy for remodeling the joint microenvironment: mechanisms, nanotechnology-enhanced strategies, and translation prospects.
Shi Y, Ni Z, Wang F … +6 more , Li Z, Li S, Li K, Chen X, Xu C, Wang F
Stem Cell Res Ther · 2026 May · PMID 42106739 · Full text
Osteoarthritis (OA) is a complex, multifactorial whole-joint disease characterized by progressive articular cartilage degeneration, synovitis, and subchondral bone remodeling. Current clinical interventions primarily off...
Osteoarthritis (OA) is a complex, multifactorial whole-joint disease characterized by progressive articular cartilage degeneration, synovitis, and subchondral bone remodeling. Current clinical interventions primarily offer symptomatic management but do not halt or reverse disease progression. Recent advancements in regenerative medicine have emphasized mesenchymal stromal cell (MSC) therapy owing to its substantial potential in tissue repair and microenvironmental modulation. This review systematically evaluates the therapeutic efficacy and potential mechanisms of bone marrow-derived MSCs, adipose-derived stromal cells, umbilical cord-derived MSCs, synovium-derived MSCs, embryonic stem cell-derived MSCs and induced pluripotent stem cell-derived MSCs, as well as MSC-derived exosomes, in modulating the joint microenvironment. Furthermore, we discuss recent innovations in nanotechnology-enhanced strategies, designed to improve targeting specificity and therapeutic durability of MSC-based interventions. This review aims to establish a foundational framework and translational roadmap for the development of next-generation disease-modifying therapies for OA.
Mesenchymal stem cell derived exosomes mitigate COVID-19 cytokine storm via Annexin A1 and TGF-β mediated MAPK pathway inhibition.
Ebrahim N, Al Saihati HA, Dessouky AA … +8 more , Ismail YM, Shamaa AA, Mohamed SA, Mohamed ME, Nosseir N, Eladl MA, Di Leva G, Badr OA
Stem Cell Res Ther · 2026 May · PMID 42104510 · Full text
BACKGROUND: Severe COVID-19 is marked by a dysregulated inflammatory response, known as a cytokine storm, resulting in acute respiratory distress syndrome (ARDS) and multiple organ failure. Mesenchymal stem cell-derived...
BACKGROUND: Severe COVID-19 is marked by a dysregulated inflammatory response, known as a cytokine storm, resulting in acute respiratory distress syndrome (ARDS) and multiple organ failure. Mesenchymal stem cell-derived exosomes (MSC-Exos) have demonstrated potential as immunomodulatory agents. This work investigates the possibility of MSC-Exos to mitigate excessive inflammation in COVID-19 by targeting the mitogen-activated protein kinase (MAPK) signalling pathway. METHODOLOGY: We integrated molecular docking analysis between TGF-β and Annexin A1 as exosomal proteins and key component proteins of the MAPK pathway (p38, ERK1/2, JNK1). The in-silico results were then validated in vivo using a Syrian hamster model of SARS-CoV-2 infection. Quantitative PCR (qPCR), western blotting, and histological examination were employed to evaluate the effects of MSC-Exos therapy on MAPK pathway activation, cytokine production, and lung tissue pathology. RESULTS: The in-silico study revealed extensive hydrogen bonding and hydrophobic interactions at the protein-protein interfaces between exosomal proteins and MAPK components. These interactions suggest that exosomal proteins may modulate MAPK signaling pathways. In vivo, MSC-Exos administration led to marked downregulation of pivotal genes in the MAPK signaling pathway (MEKK1, MEKK2, MEKK3), diminished phosphorylation of JNK1, p38, and ERK1/2, and lowered production of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Histopathological examination demonstrated ameliorated lung tissue structure, characterized by diminished alveolar wall thickness and decreased immune cell infiltration. CONCLUSION: MSC-Exos elicit immunomodulatory effects in SARS-CoV-2-Infected hamsters, partially by directly targeting and blocking the MAPK signaling pathway. These findings offer a compelling justification for the clinical assessment of MSC-Exos as a therapeutic approach to alleviate the cytokine storm and enhance outcomes in severe COVID-19 by targeting the ACE2-Independent pathway.
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