Stem Cell Res Ther [JOURNAL]
Sun
200 papers
Therapeutic potential of mesenchymal stromal cells in COVID-19: a meta-analysis of clinical trials conducted since the pandemic onset.
Yuan MQ, Pan YF, Zhang ZY … +9 more , Wu YX, Zhu KD, Wang ZR, Zhang ZY, Xiong JQ, Xu Z, Huang L, Wang FS, Shi L
Stem Cell Res Ther · 2026 Apr · PMID 42035205 · Full text
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can induce immune dysregulation and multi-organ injury; mesenchymal stromal cell (MSC) therapy has shown promise in clinical trials for C...
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can induce immune dysregulation and multi-organ injury; mesenchymal stromal cell (MSC) therapy has shown promise in clinical trials for COVID-19 and may have broader applicability to pneumonia induced by respiratory viruses (e.g., the influenza virus). This meta-analysis synthesized the available comparative clinical evidence on the safety and efficacy of MSCs in patients with moderate to critical COVID-19 and examined the reported outcomes relevant to Long-COVID. METHODS: We searched the PubMed, Embase, and CNKI databases for original, comparative studies in moderate, severe, or critical COVID-19 published up to September 2, 2024. Twenty-four eligible studies (13 RCTs and 11 non-randomized controlled trials; n = 1080) were included in the mortality meta-analysis. Patients were assigned to either the intervention group (MSC therapy plus standard care) or the control group (standard care with or without placebo). The primary efficacy outcome was all-cause mortality, while the primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs). Secondary outcomes included clinical recovery, hospitalization metrics, chest imaging, and inflammatory biomarkers. We performed a pooled meta-analysis on mortality with subgroup analyses (by disease severity, administration route, dosing frequency, and study design), assessment of publication bias (using funnel plots and Egger's test), and evaluation of the quality of evidence via the GRADE approach. AEs/SAEs were analyzed using meta-analysis and descriptive statistics, while other secondary outcomes were summarized descriptively. RESULTS: MSC therapy significantly reduced all-cause mortality (MSC: 26.4% vs control: 31.9%; fixed-effect OR = 0.74, 95% CI 0.55-0.99), with low heterogeneity (I = 2.8%, P =0.422[Q-test]) and no publication bias. The quality of evidence was moderate (according to the GRADE assessment). The subgroup analysis revealed a significant survival benefit in severe/critical patients (OR = 0.73, 95% CI 0.54-0.98) but not in studies that included moderate cases (OR = 0.91, 95% CI 0.23-3.65). No significant heterogeneity was found across study designs, administration routes, or dosing frequencies, which confirmed the robustness of the primary findings while indicating insufficient evidence to determine the optimal regimen. The secondary outcomes suggested improvements in clinical recovery, pulmonary function, and pro-/anti-inflammatory cytokine balance in patients that received MSC therapy. Limited studies with long-term follow-up indicated potential benefits for Long-COVID outcomes (e.g., fatigue, quality of life, residual CT abnormalities, and exercise tolerance). No significant differences were observed in AEs or SAEs post-MSC infusion, which suggested that MSC therapy was well tolerated. CONCLUSION: This meta-analysis indicated that MSC therapy may reduce mortality in patients with severe or critical COVID-19, demonstrating a favorable safety profile and potential benefits for Long-COVID and other viral pneumonias. Further large-scale, rigorous RCTs and mechanistic studies are warranted to strengthen the evidence base and standardize MSC administration regimens (source, dosing, frequency, and intervals) for managing COVID-19, Long-COVID, and other viral pneumonias.
PW1 cells give rise to cardiac adipocytes during development and myofibroblasts following injury.
Wei Y, Kou S, Qin L … +7 more , Deng D, Zhang W, Meng J, Feng T, Liu C, Tang J, Zhang H
Stem Cell Res Ther · 2026 Apr · PMID 42035143 · Full text
BACKGROUND: Pw1, a maternally imprinted gene, is expressed in various stem cell populations, underscoring its crucial roles in tissue development, maintenance, and regeneration. While our recent work has revealed its reg...
BACKGROUND: Pw1, a maternally imprinted gene, is expressed in various stem cell populations, underscoring its crucial roles in tissue development, maintenance, and regeneration. While our recent work has revealed its regulatory function in cardiac fibrosis following ischemic injury, whether PW1 cells exhibit stem cell properties in the heart remains unclear. METHODS: We utilized genetic lineage tracing with Pw1;R26-tdT and Pw1;R26-tdT mouse models. The adipogenic and fibrogenic potential of PW1 cells was assessed in vitro using sorted tdTomato cells subjected to differentiation assays. In vivo fate mapping was performed during postnatal development and after myocardial infarction (MI) induced by permanent coronary artery ligation. Single-cell RNA sequencing data from adult mouse hearts were reanalyzed to characterize Pw1 expression across cardiac cell types. RESULTS: PW1 was expressed in multiple cardiac cell types-such as mesenchymal cells, epicardial cells, and endothelial cells-during early postnatal development. Isolated PW1 cells from infant hearts differentiated into adipocytes in vitro, and lineage tracing experiments confirmed their significant contribution to cardiac adipocyte formation throughout postnatal development. Single-cell transcriptomic analysis further revealed predominant Pw1 expression in adult cardiac fibroblasts. In vitro, adult PW1 cells differentiated into myofibroblasts upon TGFb1 stimulation and showed upregulated expression of extracellular matrix genes and TGFb receptors. After MI, PW1 cells preferentially expanded and contributed to the myofibroblast population within the infarcted region. CONCLUSION: This study reveals that PW1 cells serve as a progenitor population capable of generating cardiac adipocytes during postnatal development and contributing to myofibroblast formation after MI. These findings offer new insights into cardiac adipogenesis and fibrogenesis, providing a potential foundation for future therapies aimed at mitigating pathological adipose accumulation and fibrosis in the heart.
Phase-dependent efficacy of intravenous amniotic mesenchymal stem cells in a rat spinal cord injury model.
Qi Y, Kawabori M, Yamaguchi S … +4 more , Nakahara Y, Li Z, Ohtsuki S, Fujimura M
Stem Cell Res Ther · 2026 Apr · PMID 42032754 · Full text
BACKGROUND: Spinal cord injury results in profound neurological disability driven initially by primary mechanical damage and subsequently by secondary injury processes characterized by progressive neuroinflammation. Intr...
BACKGROUND: Spinal cord injury results in profound neurological disability driven initially by primary mechanical damage and subsequently by secondary injury processes characterized by progressive neuroinflammation. Intravenous administration of human amniotic mesenchymal stem cells (MSC) has emerged as a promising therapeutic approach; however, the optimal timing of administration and its relationship to dynamic immune responses remain unclear. METHODS: A rat contusion model of spinal cord injury was used to evaluate the effects of intravenous MSC administration at three post-injury time points: days 1, 3, and 7. Functional and histological assessments were performed for each group. Systemic inflammatory responses were evaluated through blood analysis of neutrophil and macrophage counts, systemic inflammation index (SII), and plasma proteomics. Local immune responses were assessed by quantifying infiltrating immune cells within the injured spinal cord. RESULTS: The most substantial improvement in locomotor function was observed in the day-1 treatment group, followed by the day-7 group, whereas the day-3 group showed minimal benefit. The day-3 group also demonstrated a trend toward greater lesion length and increased macrophage infiltration 28 days after injury. MSC administration reduced SII in the day-1 and day-7 groups but not in the day-3 group, which instead showed an increased systemic inflammatory response. Analysis of spinal cord tissue demonstrated that MSC treatment on day-1 effectively reduced neutrophil infiltration, which peaks at this time point, while day-7 administration reduced macrophage infiltration during its peak phase. In contrast, MSC administration on day-3 failed to attenuate either neutrophil or macrophage accumulation. Plasma proteomic profiling revealed enhanced complement and coagulation pathway activation specifically on day-3. CONCLUSIONS: The therapeutic efficacy of intravenously administered MSC is highly dependent on the timing of intervention. Optimal benefit is achieved when treatment coincides with peak activation of a dominant target immune cell population and avoids the peak of complement and coagulation signaling. These findings support a phase-matched therapeutic strategy to maximize MSC effectiveness following spinal cord injury.
IL-1β modulates inflammatory response of human bone marrow-derived MSCs and neutrophil recruitment in vitro via NF-kB-associated signaling.
Hassaan N, Schmidt T, Söderlund Z … +6 more , Kalafatis D, Påhlman LI, Scheding S, Weiss DJ, Kahn R, Rolandsson Enes S
Stem Cell Res Ther · 2026 Apr · PMID 42032676 · Full text
BACKGROUND: The variable clinical outcomes of mesenchymal stromal cell (MSC)-based therapy in acute respiratory distress syndrome (ARDS) are attributed to a variety of factors, including host microenvironmental factors....
BACKGROUND: The variable clinical outcomes of mesenchymal stromal cell (MSC)-based therapy in acute respiratory distress syndrome (ARDS) are attributed to a variety of factors, including host microenvironmental factors. Interleukin-1β (IL-1β) has been linked to the development and progression of ARDS, and we have previously found that IL-1β could be used to predict MSC activation in vitro. However, the exact mechanisms through which IL-1β alters the MSC function and its interaction with the host immune cells remains unknown. Therefore, the aim of this study was to assess how IL-1β alters MSC function, with a specific focus on MSC-neutrophil interaction. METHODS: Human bone marrow-derived MSCs were exposed to 20 ng/ml IL-1β for 1 or 24 h. Following exposure, MSCs were analyzed using bulk RNA sequencing and key secretome proteins were measured in their conditioned medium. A transwell culture system was used to evaluate the neutrophil recruitment capacity of IL-1β-exposed MSCs, with or without NF-kB inhibition. MSCs exposed to serum free medium were used as controls in all experiments. RESULTS: The sequencing data revealed that genes involved in response to biotic stimuli and immune response were altered in MSCs exposed to IL-1β compared to control cells. In particular, genes essential for neutrophil recruitment were significantly upregulated after IL-1β exposure. The functional in vitro studies further validated these results, demonstrating that MSCs exposed to IL-1β had a significantly higher neutrophil recruitment capacity compared to unstimulated MSCs. Finally, inhibition of the NF-kB pathway resulted in a significant decrease of the MSC's capacity to recruit neutrophils to levels similar as to the unstimulated control MSCs. CONCLUSION: These data provide mechanistic insight into how inflammatory factors present in the host microenvironment might affect the interaction between MSCs and immune cells. This further highlights the need to understand the MSC mode of action, and to map out how the MSC fate might change in different host environments after administration.
Investigation of the clinical efficacy of mesenchymal stem cells in combination with monoclonal antibody therapy against feline panleukopenia.
Wang Y, Yan R, Mao L … +5 more , Wang H, Zhu C, Wang D, Ding Y, Wang D
Stem Cell Res Ther · 2026 Apr · PMID 42026664 · Full text
BACKGROUND: Feline panleukopenia is an acute and highly contagious disease caused by feline panleukopenia virus (FPV). Conventional therapeutic approaches often yield suboptimal outcomes in managing leukopenia, which con...
BACKGROUND: Feline panleukopenia is an acute and highly contagious disease caused by feline panleukopenia virus (FPV). Conventional therapeutic approaches often yield suboptimal outcomes in managing leukopenia, which consequently contributes to its high mortality rate. Mesenchymal stem cells (MSCs) are a type of multipotent stem cell characterized by their multidirectional differentiation potential and immunomodulatory capabilities. Studies have shown that MSCs possess the potential to treat inflammatory and immune-mediated diseases, support and promote hematopoiesis, and facilitate tissue repair. Therefore, this study was to investigate the clinical efficacy of combining MSCs with feline panleukopenia monoclonal antibody to propose a potential treatment for FPV. METHOD: MSCs were extracted from a newborn kitten's umbilical cord tissue. Fifteen healthy unimmunized kittens aged 2 to 4 months were divided evenly into three groups: control group, conventional treatment group, and MSCs group (conventional treatment combined with MSCs therapy, involving daily intravenous administration of 1 × 10 MSCs for 3 consecutive days). Treatments were commenced once evident clinical symptoms manifested and white blood cell counts declined below the normal range. The subject cats were assessed for clinical signs, complete blood count (CBC), blood biochemistry, serum amyloid A (SAA), pathology and viral load in major organs. RESULT: The results revealed that in the control group and conventional treatment group, cats exhibited a rapid decline in white blood cell count following disease onset, ultimately resulting in mortality. Conversely, in the MSCs group, four cats demonstrated an increase in white blood cell count post-treatment, subsequently returning to normal levels. However, one cat did not exhibit a significant increase and died on the third day of treatment. CONCLUSION: These findings highlight the therapeutic potential of MSCs in elevating leukocyte counts, improving clinical symptoms, and ultimately leading to a significant enhancement of survival rates among FPV-affected cats.
Application of dendritic cell extracellular vesicles as a valid nanoparticle platform for cancer therapies: a narrative review.
Nezamdoust FV, Nezhad-Mokhtari P, Mirzaahmadi B … +3 more , Mazloumi Z, Kangari P, Rahbarghazi R
Stem Cell Res Ther · 2026 Apr · PMID 42010708 · Full text
The prevalence of cancers has actually increased during the last few decades, affecting almost all human societies. Despite progress in therapeutic protocols, cancer is still the main cause of global human mortality. Alt...
The prevalence of cancers has actually increased during the last few decades, affecting almost all human societies. Despite progress in therapeutic protocols, cancer is still the main cause of global human mortality. Although the advancement of modern immunotherapeutic approaches can increase the survival rate of cancer patients, new modalities are essential for improved therapeutic outcomes. Extracellular vesicles (EVs) are nanosized particles and are used for cell-free approaches instead of direct whole cell-based administration. It has been thought that EVs can reduce the risks and side effects of immunotherapy. Dendritic cells (DCs), belonging to antigen-presenting cells (APCs), are present in different parts of the body with the fundamental activity against tumors and various inflammatory conditions. Due to the existence of reconfigurable contents, DC EVs are valid bioshuttles to transfer immunogenic molecules, process antigens along with co-regulatory factors to other immune cell subsets like T lymphocytes, involved in the control of immune responses in a paracrine manner. Besides, recent technologies have enabled us to produce engineered DC EVs with higher immunotherapeutic potential against the tumor cells. In the current review article, we aimed to discuss recent developments in nanomedicine and biotechnology fields for the application of DC EVs in terms of cancer. The recent data will help the researchers and clinicians to understand the underlying mechanism associated with the tumoricidal properties of DC EVs and the development of a new delivery system in cancer conditions. Besides, the application of sophisticated modalities and technologies can help in the large-scale production of engineered DC EVs for the alleviation of cancer-related pathologies in the clinical setting with high-rate regenerative outcomes.
TGF-β/SMAD signaling maintains nucleus pulposus stem cell quiescence to protect against oxidative injury in intervertebral disc degeneration.
Chen Q, Chen X, Yang Q … +7 more , Miao X, Yuan J, Ding S, Ding R, Cai S, Li B, Cheng X
Stem Cell Res Ther · 2026 Apr · PMID 42010638 · Full text
BACKGROUND: Intervertebral disc degeneration (IVDD) is characterized by progressive nucleus pulposus cell loss and extracellular matrix degradation, in which persistent oxidative stress plays a critical pathogenic role....
BACKGROUND: Intervertebral disc degeneration (IVDD) is characterized by progressive nucleus pulposus cell loss and extracellular matrix degradation, in which persistent oxidative stress plays a critical pathogenic role. Transplantation of nucleus pulposus-derived stem cells (NPSCs) is a promising therapeutic strategy, yet the hostile oxidative microenvironment severely compromises cell survival. Although cellular quiescence has been suggested to enhance stress tolerance, its regulatory mechanisms and relevance in NPSCs remain largely unexplored. METHODS: Oxidative stress was evaluated in human degenerated disc tissues, a rat needle-puncture degeneration model, and tert-butyl hydroperoxide-treated NPSCs in vitro. Proliferating and quiescent NPSCs were compared for reactive oxygen species (ROS) levels, apoptosis, viability, and transcriptomic profiles. Pathway enrichment analyses were performed to identify critical signaling mechanisms. Recombinant transforming growth factor-beta 3 (rhTGF-β3) was used to activate the pathway, while small interfering RNA targeting the transforming growth factor-beta receptor type 2 (Tgfbr2) and the pharmacological inhibitor SB431542 were applied for pathway suppression. Functional assays, organ culture, and in vivo transplantation were conducted to assess cell survival and regenerative effects. RESULTS: Elevated oxidative stress was consistently observed across clinical, animal, and cellular models of disc degeneration. Quiescent NPSCs demonstrated enhanced resistance to oxidative injury, with reduced ROS accumulation, decreased apoptosis, and improved survival. Transcriptomic analyses revealed suppression of metabolic and P53-mediated apoptotic pathways, alongside marked activation of TGF-β/SMAD signaling. Activation of this pathway induced quiescence, reduced ROS levels, inhibited mitochondrial apoptotic signaling, and protected NPSCs from oxidative injury, whereas pathway inhibition abolished these protective effects. In both organ culture and in vivo transplantation models, quiescent and TGF-β-activated NPSCs exhibited superior survival and significantly improved disc structural preservation compared with proliferating or pathway-blocked cells. CONCLUSION: Activation of the TGF-β/SMAD pathway induces NPSC quiescence and enhances oxidative stress tolerance by suppressing P53-dependent mitochondrial apoptosis. Pharmacological induction of quiescence represents a potential strategy to improve stem cell-based therapies for intervertebral disc degeneration.
Adipose-derived regenerative cell therapy mitigates sepsis-induced cardiomyopathy through the induction of cardiac reparative lymphangiogenesis.
Luo H, Shimizu Y, Chen X … +5 more , Liu T, Che Y, Matsuoka Y, Yamaguchi S, Murohara T
Stem Cell Res Ther · 2026 Apr · PMID 42002800 · Full text
BACKGROUND AND PURPOSE: Sepsis-induced cardiomyopathy (SICM) represents a critical unmet clinical challenge globally and is highlighted by the paucity of effective therapeutic interventions. Despite its clinical importan...
BACKGROUND AND PURPOSE: Sepsis-induced cardiomyopathy (SICM) represents a critical unmet clinical challenge globally and is highlighted by the paucity of effective therapeutic interventions. Despite its clinical importance, the exacerbating factors and intricate underlying mechanisms remain largely unknown. Emerging evidence has highlighted the pivotal role of the cardiac lymphatic vasculature in cardiac homeostasis and repair, prompting investigations into its contributions during pathological states. In this study, we delineated the dynamics and functional significance of cardiac lymphatic vessels in SICM pathogenesis, and evaluated the therapeutic efficacy of targeted lymphangiogenesis as a novel strategy to improve poor prognosis. METHODS AND RESULTS: Using a lipopolysaccharide (LPS)-induced SICM mouse model, the evolution of cardiac lymphatic kinetics and observed reparative lymphangiogenesis was assessed in SICM. In addition, pharmacological inhibition of reparative lymphangiogenesis further exacerbated mortality rates in this model, thus highlighting its protective contributions. Adipose-derived regenerative cells (ADRCs) robustly enhance lymphangiogenesis in cardiac tissues during SICM. In vitro assays with lymphatic endothelial cells (LECs) confirmed that this lymphangiogenic potency is mediated, at least in part, by vascular endothelial growth factor-C (VEGF-C) secreted by ADRCs. Notably, ADRC-mediated therapeutic lymphangiogenesis restored cardiac function and mitigated adverse pathological remodeling as well as significantly improved the overall prognosis in SICM-affected animals. CONCLUSION: Our findings highlight the essential role of cardiac lymphatic vessels in improving SICM outcomes and indicate that ADRC-driven therapeutic lymphangiogenesis is a promising and innovative modality for treating this highly severe condition.
BMSCs regulate RGS3 expression in ovarian stromal cells to improve ovarian stromal fibrosis and angiogenic microenvironment in cyclophosphamide-induced premature ovarian failure.
Guo Z, Li P, Yang D … +5 more , Li J, Sun X, Qiao P, Yuan W, Du P
Stem Cell Res Ther · 2026 Apr · PMID 42002799 · Full text
BACKGROUND: Mesenchymal stem cells have been shown to attenuate chemotherapy induced premature ovarian failure (POF) in rats, although the underlying molecular mechanisms remain poorly defined. This study was designed to...
BACKGROUND: Mesenchymal stem cells have been shown to attenuate chemotherapy induced premature ovarian failure (POF) in rats, although the underlying molecular mechanisms remain poorly defined. This study was designed to explore the effects of bone marrow derived mesenchymal stem cells (BMSCs) on ovarian stromal cells (SCs) in a POF model, and to determine whether regulator of G protein signaling 3 (RGS3) acts as a key mediator in regulating ovarian stromal fibrosis and follicular angiogenesis, ultimately improving the follicular developmental microenvironment. METHODS: BMSCs and SCs were isolated from Wistar rats and cultured. A cyclophosphamide (CTX) -induced SCs injury model was established in vitro. BMSCs were co-cultured with injured SCs using transwell inserts. For the in vivo study, 48 female Wistar rats were randomly divided into three groups: control, CTX model, and CTX+BMSCs treatment group. BMSCs were administered via tail vein injection. Ovarian tissue morphology and fibrosis were assessed using hematoxylin and eosin (HE) staining, Masson's trichrome staining, and transmission electron microscopy. The expression levels of RGS3, VEGF, CD31, TGF-β1, p-Smad2/3, α-SMA, and Vimentin were detected by immunohistochemistry and Western blot. To investigate the regulatory role of RGS3 in the TGF-β1/Smad2/3 pathway and VEGF expression in theca cells (TCs), RGS3 was silenced using siRNA. RESULTS: In vitro experiments showed that CTX treatment significantly downregulated the expression of RGS3 and VEGF in SCs, while upregulating TGF-β1 expression. These changes were reversed by co-culture with BMSCs. In vivo experiments revealed that CTX-induced POF rats exhibited irregular estrous cycles, a reduced number of follicles, and increased deposition of interstitial collagen fibers. Consistently, the expression levels of α-SMA and Vimentin were increased, while RGS3, VEGF, and CD31 were decreased. The TGF-β1/Smad2/3 pathway was also aberrantly activated. BMSCs transplantation significantly improved ovarian morphology, reduced collagen deposition, and restored the regularity of the estrous cycle. Furthermore, BMSCs transplantation reversed the CTX-induced protein expression changes by upregulating RGS3, VEGF, and CD31, and inhibiting the activation of the TGF-β1/Smad2/3 pathway. Finally, silencing RGS3 with siRNA exacerbated the CTX-induced effects in theca cells (TCs), leading to a further decrease in VEGF expression and a further increase in TGF-β1/Smad2/3 expression. CONCLUSIONS: BMSCs may target RGS3 to coordinately regulate the expression of TGF-β1/Smad2/3 and VEGF. This regulatory axis modulates SCs differentiation and angiogenesis, reduces ovarian stromal fibrosis, and improves the ovarian developmental microenvironment.
DMOG pretreatment restores osteogenic-adipogenic balance and mitochondrial function in ONFH BMSCs through the HIF-1α/Homer3 pathway.
Chen Q, Yi L, Nie P … +4 more , Wang J, Zhu J, Peng J, Weng T
Stem Cell Res Ther · 2026 Apr · PMID 42002787 · Full text
BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a progressive orthopedic disorder that often culminates in femoral head collapse and joint failure. Dysfunction of bone marrow mesenchymal stem cells (BMSCs), inclu...
BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a progressive orthopedic disorder that often culminates in femoral head collapse and joint failure. Dysfunction of bone marrow mesenchymal stem cells (BMSCs), including impaired osteogenesis, enhanced adipogenesis, and mitochondrial dysfunction, has been increasingly recognized as a central driver of ONFH pathogenesis. However, the molecular mechanisms linking metabolic stress to lineage imbalance remain poorly defined. METHODS: Paired BMSCs were isolated from necrotic femoral head regions (fhBMSCs) and the iliac crest (iBMSCs) of ONFH patients. Functional assays, RNA sequencing, and molecular analyses were performed to evaluate the effects of the hypoxia mimetic dimethyloxalylglycine (DMOG) on osteogenic-adipogenic balance, mitochondrial function, and senescence. Loss-of-function experiments targeting hypoxia-inducible factor-1α (HIF-1α) and Homer3 were conducted to elucidate mechanistic pathways. RESULTS: Compared with iBMSCs, fhBMSCs exhibited impaired osteogenesis, enhanced adipogenesis, mitochondrial dysfunction, and increased senescence. DMOG pretreatment restored osteogenic differentiation, suppressed adipogenesis, improved mitochondrial dynamics, reduced oxidative stress, and enhanced bioenergetic metabolism. These protective effects were dependent on HIF-1α stabilization. Transcriptomic profiling identified Homer3 as a downstream negative regulator of HIF-1α. Homer3 was aberrantly upregulated in fhBMSCs but suppressed by DMOG, and its knockdown mimicked the effects of DMOG by promoting osteogenesis, inhibiting adipogenesis, enhancing mitophagy, and restoring mitochondrial function. Conversely, silencing HIF-1α abolished DMOG-mediated benefits and reinstated Homer3 expression. CONCLUSIONS: This study identifies the HIF-1α/Homer3 axis as a central regulator of lineage balance and mitochondrial homeostasis in ONFH-derived BMSCs. Pharmacological targeting of this pathway with DMOG or related prolyl hydroxylase inhibitors may provide a promising joint-preserving therapeutic strategy for ONFH.
The messenger ion: magnesium ion coordinates bone marrow mesenchymal stem cells-mediated osteogenesis, migration, and angiogenesis via the PI3K-AKT-mTOR pathway.
Huang L, Pei Z, Zhao P … +3 more , Cheng Y, Wu Q, Wen L
Stem Cell Res Ther · 2026 Apr · PMID 42002781 · Full text
BACKGROUND: Magnesium (Mg) and its alloys, as biodegradable metallic materials, possess numerous advantageous properties compared to traditional biomaterials. Furthermore, magnesium ions (Mg²⁺) are the second most abunda...
BACKGROUND: Magnesium (Mg) and its alloys, as biodegradable metallic materials, possess numerous advantageous properties compared to traditional biomaterials. Furthermore, magnesium ions (Mg²⁺) are the second most abundant intracellular cations, participating in over 300 enzymatic reactions and serving as essential trace elements for various physiological processes. The release of Mg²⁺ is believed to promote osteogenic differentiation and angiogenesis, both of which are crucial for bone regeneration. However, the mechanisms underlying Mg²⁺-mediated promotion of osteogenesis and angiogenesis are not yet fully elucidated. METHODS: We treated Bone marrow mesenchymal stem cells (BMSCs) with Mg²⁺ and performed transcriptome sequencing on both control and experimental groups. Bioinformatics analysis was conducted using the sequencing data, including principal component analysis, differential expression analysis, enrichment analysis, and protein-protein interaction analysis. Pathway proteins were assessed by Western blot. The osteogenic capacity of BMSCs was directly evaluated using ALP and ARS staining. Immunofluorescence staining was used to detect the expression of osteogenesis-related proteins RUNX2 and OPN. Tube formation assays were employed to evaluate the effect of magnesium ions on angiogenesis capability, while Western blotting and quantitative PCR were used to assess changes in FGF2 and CD31 expression levels. Concurrently, the functional impact of Mg²⁺ on BMSCs was assessed using Transwell and CCK8 assays. Finally, we established a bone defect model in rats and implanted magnesium alloy scaffolds to verify the conclusions drawn from the in vitro experiments. RESULT: Through bioinformatics analysis, we identified the PI3K-AKT-mTOR pathway as a potential key pathway through which Mg²⁺ promotes osteogenesis and angiogenesis in BMSCs. Magnesium ion treatment enhanced the activity of pPI3K, pAKT, and pmTOR, elevated the expression of osteogenic and angiogenic proteins, increased ALP activity and mineralized nodule formation, and promoted tube-like structure formation. Additionally, the migratory ability, cell viability, and osteogenic activity of BMSCs were significantly elevated. Conversely, intervention with the activation of PI3K and mTOR directly affected the aforementioned outcomes, In vivo experiments also confirmed the above findings. CONCLUSION: This study confirms that Mg²⁺ synergistically promotes osteogenic differentiation, migration of BMSCs, and angiogenesis of vascular endothelial cells by activating the PI3K-AKT-mTOR pathway. By adopting the "activation-inhibition-reversal" experimental framework and conducting in vitro and in vivo validations, the critical upstream role of PI3K and the downstream effector function of mTOR were established. These findings reveal a unified mechanism by which Mg²⁺ coordinates bone regeneration via a single signaling pathway, providing a theoretical foundation for developing smart Mg-based bone repair materials targeting this pathway.
An open phase I/IIa study evaluating safety, patient-reported outcomes and voice function after surgery, local administration of mesenchymal stromal cells and voice training in patients with vocal fold scarring and dysphonia.
Bergström Börlin E, Nygren U, Södersten M … +5 more , Granqvist S, Kadri N, Rasmusson Duprez I, Le Blanc K, Hertegård S
Stem Cell Res Ther · 2026 Apr · PMID 42002761 · Full text
BACKGROUND: Damage to the vocal folds can result in scarring, leading to chronic, severe voice impairments for which lasting and effective treatments are currently lacking. The aim of this clinical trial was to evaluate...
BACKGROUND: Damage to the vocal folds can result in scarring, leading to chronic, severe voice impairments for which lasting and effective treatments are currently lacking. The aim of this clinical trial was to evaluate the safety and effectiveness of autologous bone marrow-derived Mesenchymal Stromal Cell (MSC) therapy for patients with vocal fold scarring and severe dysphonia. Additionally, the study sought to propose a post-operative voice training protocol and explore its potential role in facilitating voice improvement. METHODS: Eight patients with vocal fold scarring and chronic dysphonia underwent surgical scar resection and autologous MSC injection, followed by voice training. Safety was continuously monitored for up to 36 months postoperatively. Data to evaluate therapeutic efficacy was collected pre-treatment, 3 and 12 months post-treatment. Assessments included analysis of vocal fold vibrations, Phonation Threshold Pressure, and Maximum Phonation Time. Patient-reported measures were collected using the Voice Handicap Index, the Vocal Fatigue Index, and ratings of major symptoms and their impact on daily life. Treatment effectiveness was analyzed at both group and individual levels, with clinically relevant changes predefined. RESULTS: No treatment-related side effects were reported within the 36 months of follow-up. Group-level analysis of the self-reported outcomes indicated positive treatment effects, with Voice Handicap Index scores reduced by −25.9 points (95% CI [−48, −3.6]) between pre-treatment and 12 months post-treatment. Group-level aerodynamic changes were small with Phonation Threshold Pressure showing a marginal positive change on average (−0.94 cmH₂O), as did Maximum Phonation Time (+ 0.2 s). At the individual level, clinically relevant improvements were observed in 63–88% of patients depending on the parameter analyzed. Three patients (38%) achieved relevant improvement on ≥ 5/6 selected parameters in combination. All participants in voice training reported reduced vocal strain following training. CONCLUSIONS: This preliminary, uncontrolled study indicates that local administration of autologous bone marrow-derived MSCs appears safe and is associated with clinically relevant patient-reported outcome improvements in a majority of patients. Larger, controlled trials are needed in the future to establish efficacy and possibly disentangle contributions of MSCs versus voice training. TRIAL REGISTRATION : This clinical trial is registered in ClinicalTrials.gov (NCT04290182)
Mesenchymal stromal cell therapy is a long-term regenerative approach for chronic radiation cystitis, involving coordinated modulation of the urothelial, immune, vascular, and fibrotic pathways.
Pouliet AL, Côme J, Fail A … +8 more , Dos Santos M, Linard C, Demarquay C, Fleury C, Buard V, Brossard C, Milliat F, Chapel A
Stem Cell Res Ther · 2026 Apr · PMID 42002744 · Full text
BACKGROUND: Chronic radiation cystitis (CRC) is a disabling late adverse effect of pelvic irradiation, characterized by urothelial barrier loss, persistent inflammation, vascular alteration, and progressive fibrosis. No...
BACKGROUND: Chronic radiation cystitis (CRC) is a disabling late adverse effect of pelvic irradiation, characterized by urothelial barrier loss, persistent inflammation, vascular alteration, and progressive fibrosis. No curative treatment exists. Mesenchymal stromal cells (MSCs) are investigated for their regenerative potential, however their long-term mechanisms of action in CRC remain incompletely elucidated. METHODS: CRC was induced in rats by localized bladder irradiation (40 Gy). Animals were randomized into unirradiated controls, irradiated controls, and irradiated MSC-treated groups. The treated group received three intravenous injections of adipose-derived MSCs at 4.5, 5.0, and 5.5 months post-irradiation, during the pre-chronic phase. Bladders were analyzed up to 18 months post-irradiation by immunostaining and RT-qPCR for urothelial differentiation (Upk1a, Upk1b, Upk2, Upk3a, Upk3b), epithelial proliferation (CK14⁺/PCNA⁺) and fibrosis (collagen I and III). Immune activation (CD45⁺ leukocytes, neutrophils, mast cells, Gata3, Th1, Th2) was analyzed by flow cytometry and vascular integrity by cystoscopy and Cspg4, VegfA expression. RESULTS: At 18 months post-irradiation, irradiated bladders showed a 90% loss of UPK3 staining and hyperplasia (urothelium thickening) greater than 300 μm result of basal cell hyperproliferation, a ninefold increase compared to controls. MSC treatment reduced hyperplasia by 66% compared to irradiated rats, restored gene expression of Upk1a and Upk3a to 80-90% unirradiated control levels and decreased proliferative CK14⁺/PCNA⁺ progenitors by 93%). Immune response was attenuated, with a 49% reduction in Th2-associated cell infiltration and downregulation of Gata3 expression (p < 0.05) relative to irradiated rats. A decrease in mast cell degranulation (61%) was observed at neurovascular interfaces. Vascular architecture was preserved, with VegfA expression normalization and reduction of cystoscopic vascular lesions. Fibrotic remodeling was limited, with less accumulation of collagen 1 and a maintained physiological collagen 1/3 balance in the detrusor. CONCLUSION: MSC treatment had durable, multi-compartment effects in CRC. It limited basal hyperplasia, restored urothelial lineage differentiation, selectively modulated adaptive immune activation and mast cell activity, and constrained collagen 1-driven fibrosis. Vascular architecture was partially preserved, which together supported urothelial homeostasis in CRC. These findings provide strong preclinical evidence supporting MSCs as a targeted long-term regenerative strategy for CRC.
Allogeneic umbilical cord-derived mesenchymal stromal cells for treatment of refractory lupus nephritis: a real-world study.
Zheng Y, Liu S, Zeng L … +9 more , Luo Y, Jin Z, Yang D, Shi Y, Li J, Wang H, Feng X, Wang D, Sun L
Stem Cell Res Ther · 2026 Apr · PMID 42001190 · Full text
OBJECTIVES: This study aims to investigate the therapeutic effects of allogeneic umbilical cord-derived mesenchymal stromal cells (UC-MSCs) on refractory lupus nephritis (LN) and to evaluate the benefits for patients wit...
OBJECTIVES: This study aims to investigate the therapeutic effects of allogeneic umbilical cord-derived mesenchymal stromal cells (UC-MSCs) on refractory lupus nephritis (LN) and to evaluate the benefits for patients with different baseline renal functions. METHODS: A total of 120 eligible patients with refractory LN were included in this study. Primary outcomes were the rate of renal response and relapse. Secondary outcomes included laboratory parameters and prednisone dosage. Adverse events (AEs) were recorded using telephone questionnaires and the medical record system. RESULTS: Cumulative renal response rates at 3, 6, and 12 months were 38.3% (46/120), 53.3% (64/120), and 56.7% (68/120), respectively. Cumulative relapse rates at 6 and 12 months were 2.9% (2/68) and 8.8% (6/68), respectively. At the 12-month mark, estimated glomerular filtration rate (eGFR) significantly improved in chronic kidney disease stages 2 (CKD 2) and 3a (CKD 3a) patients (P = 0.032 and P = 0.046, respectively). Patients with a baseline eGFR of ≥ 45 ml/min/1.73 m² had a substantially higher renal response rate (66.3%). A baseline eGFR of ≥ 45 ml/min/1.73 m² was an independent predictor for renal response (OR = 2.104, 95% CI 1.063-4.167). One hundred twenty patients received 146 UC-MSCs infusions. Hyperacute AEs occurred in 2.1% (3/146) and infections in 10.9% (16/146). No severe AEs occurred. CONCLUSION: UC-MSCs therapy shows a favorable safety profile and promising efficacy in refractory LN, markedly reducing proteinuria and improving renal function. The therapeutic efficacy is particularly prominent for patients with a baseline eGFR ≥ 45 ml/min/1.73 m². Trial registration The Clinical Trial Number is NCT00698191.
Mapping the landscape and future directions of stem cell therapy for inflammatory bowel disease.
Gao J, Liu Y, Xia T … +2 more , He Z, Bai Y
Stem Cell Res Ther · 2026 Apr · PMID 41992341 · Full text
This study systematically analyzed 170 registered clinical trials to clarify the global development landscape of stem cell therapy for inflammatory bowel disease (IBD) and its core challenges, and put forward correspondi...
This study systematically analyzed 170 registered clinical trials to clarify the global development landscape of stem cell therapy for inflammatory bowel disease (IBD) and its core challenges, and put forward corresponding future research directions. The results showed that the research on this therapy has accelerated significantly in the past three decades, with research geographically clustered in the US, China and Spain, and severe underrepresentation of African countries. The therapy is mainly focused on Crohn's disease (CD), especially refractory perianal fistulas, and mesenchymal stem cells (MSCs) account for over 70% of the applied cell types. Among 88 completed trials, 29.5% achieved primary endpoints, showing preliminary efficacy, yet the field faces prominent challenges: 20.6% of trials were prematurely terminated, early-phase studies dominate, Phase IV trials and long-term efficacy data are scarce, primary endpoints are highly heterogeneous, pediatric research is limited, and most completed trials have unknown outcomes. To address these issues, this study proposes that the future research should prioritize international cooperation to promote research equity, standardize efficacy endpoints, integrate long-term follow-up into study designs, optimize stem cell source and administration protocols, and implement precise patient selection. Overcoming these bottlenecks is essential to establish stem cell therapy as an effective complementary treatment for refractory IBD and improve the prognosis of patients unresponsive to conventional therapies.
From collapse to comeback: Luteolin rejuvenates nucleus pulposus progenitor cells via SIRT1/ATF5-UPRmt to reverse intervertebral disc degeneration cascade.
Wu H, Zai S, You X … +8 more , Liu C, Li Z, Li Z, Mei Y, Hua B, Tao Y, Wu Y, Zhang L
Stem Cell Res Ther · 2026 Apr · PMID 41992290 · Full text
BACKGROUND: Intervertebral disc degeneration (IVDD) is a major contributor to low back pain (LBP) and one of the foremost causes of disability worldwide. Oxidative stress-induced senescence of nucleus pulposus progenitor...
BACKGROUND: Intervertebral disc degeneration (IVDD) is a major contributor to low back pain (LBP) and one of the foremost causes of disability worldwide. Oxidative stress-induced senescence of nucleus pulposus progenitor cells (NPPC) and mitochondrial dysfunction are key drivers of IVDD. The mitochondrial unfolded protein response (UPR), orchestrated by the Silent Information Regulator 1 (SIRT1)-Activating Transcription Factor 5 (ATF5) axis, plays a pivotal role in maintaining mitochondrial proteostasis. However, its involvement in IVDD remains insufficiently characterized. Luteolin (Lut), a naturally occurring flavonoid with well-documented antioxidant and anti-senescence properties, has emerged as a promising disease-modifying candidate. METHODS: We employed an integrated approach combining network pharmacology, molecular docking, and Mendelian randomization to identify and validate SIRT1 as a central target of Lut in IVDD. Human nucleus pulposus (NP) tissues spanning Pfirrmann grades II-V were analyzed to assess the expression of SIRT1 and UPR-related proteins. Functional assays in TBHP-induced NPPC senescence models were conducted to evaluate the effects of Lut on proliferation, senescence, mitochondrial function, and UPR activation, with or without SIRT1 knockdown. Finally, a puncture-induced rat IVDD model was employed to assess the therapeutic efficacy of Lut with imaging, histological, and behavioral analyses. RESULTS: Human NP specimens exhibited a progressive decline in SIRT1, ATF5, and UPR effectors (HSP60, LONP1, CLPP) with advancing degeneration grades. Lut was found to directly bind SIRT1, thereby stabilizing mitochondrial function and alleviating NPPC senescence through activation of the SIRT1-ATF5-UPR pathway. Genetic silencing of SIRT1 abolished the protective effects of Lut on cellular senescence, UPR activation, and bioenergetics. In vivo, Lut administration attenuated disc height loss, preserved extracellular matrix integrity and partially alleviated pain-like behaviors in rats with IVDD. CONCLUSION: This study establishes SIRT1 as a central therapeutic target of Lut and underscores the SIRT1-ATF5-UPR axis as a critical mechanism mediating its protective effects. By restoring mitochondrial proteostasis and delaying NPPC senescence, Lut emerges as a promising disease-modifying strategy for IVDD management.
Single-cell omics uncovers novel pathological mechanisms and therapeutic targets for congenital heart diseases: insights from integrated intercellular communication analysis.
Nguyen PT, Sahara M
Stem Cell Res Ther · 2026 Apr · PMID 41992274 · Full text
BACKGROUND: Congenital heart disease (CHD) affects approximately 1% of live births worldwide and remains the leading cause of infant mortality from congenital anomalies. Despite advances in diagnosis and therapeutics, th...
BACKGROUND: Congenital heart disease (CHD) affects approximately 1% of live births worldwide and remains the leading cause of infant mortality from congenital anomalies. Despite advances in diagnosis and therapeutics, the molecular mechanisms underlying CHD pathogenesis remain incompletely understood, limiting the development of efficient targeted therapies. Single-cell omics approaches including single-cell RNA sequencing (scRNA-seq) have revolutionized our understanding of cardiac cellular heterogeneity and intercellular signalling. This review synthesizes recent single-cell omics studies in cardiogenesis and CHD, and presents novel insights from an integrated reanalysis to identify potential therapeutic targets. METHODS: We systematically reviewed single-cell omics studies in human cardiogenesis and CHD (2019-2025), then reanalysed the Hill et al. dataset comprising 157,273 nuclei from paediatric patients across five diagnostic categories, including neonatal and infant hypoplastic left heart syndrome (HLHS), tetralogy of Fallot (TOF), dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) with healthy donor controls. We quantified cardiac-specific ligand-receptor interactions to characterize disease-specific intercellular communication networks through pathway enrichment and network topology analysis. RESULTS: Reanalysis revealed extensive remodelling of cell-cell communication networks across CHD subtypes, each displaying distinct signalling architectures. Neonatal HLHS and TOF demonstrated hyperactivation of metabolic and growth factor pathways with highly centralized endothelial cell (EC) to cardiomyocyte (CM) and cardiac fibroblast (CF) to CM networks. DCM showed selective metabolic enhancement with preserved integration. In contrast, HCM exhibited broad pathway suppression, particularly morphogen signalling, and fragmented connectivity with weakened CF-CM and EC-CM coupling. Infant HLHS represented an intermediate phenotype with suppressed Notch and extracellular matrix signalling. CONCLUSIONS: Single-cell omics studies have revealed cellular heterogeneity and disease-specific mechanisms across CHD subtypes. Our network-based reanalysis demonstrates that CHD involves not only transcriptional defects but also profound disruptions in multicellular communication, with each subtype exhibiting distinct signalling architectures. These findings provide a foundation for precision therapeutic strategies tailored to individual CHD subtypes, with future multimodal approaches accelerating clinical translation.
Pharmacological Inhibition of N-terminal methyltransferase 1 promotes myogenic differentiation and muscle regeneration in a mouse model of Duchenne muscular dystrophy.
Zhang H, He M, Asif M … +3 more , Deng Y, Huang R, Kuang S
Stem Cell Res Ther · 2026 Apr · PMID 41987340 · Full text
BACKGROUND: Duchenne muscular dystrophy (DMD), caused by mutations of the DMD gene, is a lethal degenerative disease with no cure. Stimulating myogenesis of muscle stem cells (MuSCs) represents a promising strategy to am...
BACKGROUND: Duchenne muscular dystrophy (DMD), caused by mutations of the DMD gene, is a lethal degenerative disease with no cure. Stimulating myogenesis of muscle stem cells (MuSCs) represents a promising strategy to ameliorate muscle pathology in DMD patients. Although previous work has revealed a role of N-terminal methyltransferase 1 (NTMT1) in myogenesis, its potential as a therapeutic target to ameliorate muscular dystrophy remains unexplored. METHOD: We employed GD433, a highly specific and potent pharmacological inhibitor of NTMT1, and evaluated its role in myogenesis using cell and animal models (mdx mice). C2C12 and primary myoblasts, and MuSCs were treated with GD433, and cell proliferation, differentiation, fusion, and gene expression were examined. Mdx mice were treated by intraperitoneal injection of GD433 (25 mg/kg, 5 days/week), and muscle pathology was evaluated. We finally employed co-immunoprecipitation (IP) and methylation-specific antibodies to identify NTMT1 substrates in myoblasts. RESULTS: A low dose of GD433 (300 nM) significantly enhances the differentiation and fusion of cultured C2C12 and primary myoblasts without affecting their proliferation. Similar effects are observed in myofiber-associated MuSCs. GD433 further enhances myogenic differentiation and muscle regeneration in mdx mice. Mechanistically, GD433 elevates expression of myogenic differentiation and fusion factors (Myog, Mymk, Mymx) through affecting KLHK31 methylation. Specifically, GD433 reduces the methylation level of KLHL31, promoting its interaction with MYOD and upregulating the expression of Myog, Mymk and Mymx. CONCLUSION: These results show that pharmacological inhibition of NTMT1 by GD433 promotes myogenic differentiation and enhances muscle regeneration in mdx mice. The pro-myogenic effect of GD433 is associated with reduced KLHL31 methylation, which strengthens KLHL31-MYOD interactions to upregulate genes related to myogenic differentiation. This study highlights NTMT1 inhibition as a potential therapeutic target to improve muscle repair in DMD patients.
Comparative analysis of NSG and NBSGW mice for preclinical evaluation of gene-modified human hematopoietic stem and progenitor cells.
Kuo CY, Harrington S, Campo-Fernandez B … +11 more , Wyman SK, Wu X, Zhang R, Espinoza A, de Andrade Silva BJ, Sanchez JM, Fitz-Gibbon S, Tseng CH, Pellegrini M, Bonner M, Romero Z
Stem Cell Res Ther · 2026 Apr · PMID 41987334 · Full text
Humanized mouse models are essential for evaluating the engraftment capacity and genetic integrity of gene-modified hematopoietic stem and progenitor cells (HSPCs). Here, we compared two widely used xenotransplantation p...
Humanized mouse models are essential for evaluating the engraftment capacity and genetic integrity of gene-modified hematopoietic stem and progenitor cells (HSPCs). Here, we compared two widely used xenotransplantation platforms, NSG and NBSGW mice, in the context of lentiviral vector (LVV) transduction and CRISPR/Cas9-mediated gene correction. HSPCs harboring high LVV copy numbers exhibited engraftment deficits in NSG mice that were not observed in NBSGW mice. This discrepancy highlights the potential for the NBSGW model to mask safety liabilities of LVV-modified products due to its higher overall levels of human chimerism. In contrast, CRISPR/Cas9 editing with a single-stranded oligodeoxynucleotide donor yielded comparable correction rates in both models, even across decreasing input cell doses, demonstrating that long-term repopulating hematopoietic stem cells (HSCs) retain equivalent engraftment capacity in each strain. Single-cell RNA-sequencing revealed distinct progenitor populations that were markedly under-represented in the NSG model but preserved in NBSGW recipients, emphasizing the greater capacity of NBSGW mice to better support multilineage human hematopoiesis. Together, these findings establish that both NSG and NBSGW mice are suitable for assessing long-term engraftment and gene modification outcomes in human HSPCs. However, the significantly higher percentage of human cell chimerism in the NBSGW model may obscure cell populations with engraftment deficits. Careful selection of in vivo models is therefore critical for rigorous preclinical evaluation of gene therapy products prior to clinical translation.
Interleukins decrease epithelial protein and gene expression by K14 + CD105+ equine hoof progenitor cells.
Yang Q, Lopez MJ
Stem Cell Res Ther · 2026 Apr · PMID 41987324 · Full text
BACKGROUND: Progenitor cell epithelial to mesenchymal transition (EMT) could impact healing in the epidermal-dermal junction of the equine hoof stratum internum (SI). The hypothesis of this study was that K14 + CD105+ eq...
BACKGROUND: Progenitor cell epithelial to mesenchymal transition (EMT) could impact healing in the epidermal-dermal junction of the equine hoof stratum internum (SI). The hypothesis of this study was that K14 + CD105+ equine hoof SI progenitor cells assume a mesenchymal phenotype in the presence of inflammatory interleukins in vitro. METHODS: K14 + CD105+ progenitor cell percentages isolated from proliferative scarred (fibrous) and healthy SI were quantified. Decellularized matrix was prepared from and K14 + CD105+ cells localized in healthy SI. Gene expression (CD44, CD105, E-cadherin, N-cadherin, β-catenin, K1, K10, p63, TGF-β1, -β2, -β3) and E- and N-cadherin+ cell percentages were determined in continuously cultured cells. Revitalized K14 + CD105+ cells were cultured in stromal medium with or without interleukins 2 and 6 (IL medium) or on decellularized SI matrix in stromal medium. After 21 days, cell gene expression (K1, K10, p63, β-catenin, TGF-β1, -β2, -β3), E-cadherin + and K14 + cell percentages, and medium TGF-β1 levels were measured. RESULTS: Most cells from healthy and fibrous SI were K14 + CD105+, and K14 and CD105 antigens were present on cells in situ and in vitro. K14 + CD105+ equine hoof SI progenitor cells maintained the immunophenotype over multiple cell passages in vitro. E-cadherin+ cell percentages were higher and K1 expression lower in K14 + CD105+ versus unsorted cells and more K14 + CD105+ cells were E- versus N-cadherin+. K14 + CD105+ cells cultured on matrix had the highest E-cadherin+ cell percentage and p63 and K10 gene expression. Cell TGF-β2 and β-catenin expression was highest with stromal medium, and cell TGFβ-1 and TGF β-3 expression was lowest with IL medium and on matrix, respectively. Cell TGF-β2, TGF-β3 and β-catenin expression was lower on matrix versus in stromal medium. Cells in IL medium had higher TGF-β3 expression than those on matrix. TGF- β1 levels were lower in IL versus stromal medium. CONCLUSIONS: The cell genetic and antigen profiles suggest that inflammatory interleukins drive mesenchymal differentiation while healthy matrix supports epidermal differentiation. K14 + CD105+ progenitor cells from the SI epidermal-dermal niche provide a platform to elucidate progenitor cell EMT capabilities and restore normal tissue healing. These findings have important implications for improving treatment strategies for injuries and disease of the epidermal-dermal junction.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe