Addressing hair damage is essential for maintaining overall hair and scalp health. Previous studies have suggested that low-molecular-weight collagen peptides may support hair follicle biology through regulation of extracellular matrix homeostasis and cellular signaling pathways. In addition, recent preclinical studies have demonstrated that low-molecular-weight fish collagen peptides promote hair regrowth through activation of proliferative signaling and suppression of inhibitory pathways. However, their clinical efficacy in improving hair damage has not been clearly established. In this study, the efficacy and safety of low-molecular-weight collagen peptide GT (LMWCP GT) were evaluated in Korean adults with damaged hair. In a randomized, placebo-controlled trial, individuals aged 19∼60 years without alopecia but with mild to moderate hair damage received LMWCP GT (3 g/day) for 24 weeks. Compared with placebo, the treatment group demonstrated significant improvements in hair gloss, as measured using a gloss meter (SAMBA) and scanning electron microscopy, as well as in hair elasticity, assessed by tensile strength and hair diameter. Subjective evaluations further indicated improvements in overall hair condition, including gloss, elasticity, thickness, texture, fullness, and appearance. In addition, scalp elasticity was significantly increased in the treatment group. No treatment-related adverse events were observed. These findings indicate that daily supplementation with LMWCP GT (3 g/day) for 24 weeks is safe and effective in improving overall hair condition in individuals with damaged hair without alopecia.
The clinical application of mesenchymal stem cells (MSCs) has several limitations owing to their less therapeutic efficacy. Effect enhancement and MSCs from new sources might help in overcoming these limitations. The aim of the present study was to investigate the therapeutic effects of human Wharton's jelly-derived MSCs (hWJMSCs) and pioglitazone-pretreated MSCs (Pio-MSCs) in a rat tendon injury model. Fifty-four Sprague Dawley rats were randomly assigned to three groups: phosphate-buffered saline (PBS) group, implanted with PBS; MSC group, implanted with MSCs; and Pio-MSC group, implanted with Pio-MSCs. The cell or PBS with fibrin glue mixture was implanted around bilateral window defect in the Achilles tendons of the rats. The cross-sectional area measurement, histological analysis, gene expression, protein expression, and biomechanical analysis were performed at 2 and 4 weeks after modeling. Pio-MSC group revealed a significantly higher gene expression level of Col3 than PBS group at 2 weeks and that of TnC at 2 and 4 weeks. Moreover, MSC group revealed significantly higher gene expression level of Col1 than PBS group at 2 weeks. In general, the expression levels of Col1, Col3, Scx, and TnC were the highest in Pio-MSC group, followed by MSC and PBS groups. Furthermore, Pio-MSC group revealed significantly higher tenascin C-stained fraction than PBS group at 4 weeks. These findings suggest a potential role of hWJMSCs in tendon regeneration; however, the in vivo enhancement effect of pioglitazone pretreatment over MSC alone was not confirmed, and no differences were observed in histological or biomechanical outcomes among the groups.
As human longevity continues to increase globally, the prevalence of age-related deterioration and associated chronic lung diseases has risen in parallel. Unlike many organs, the lung is continuously exposed to environmental insults, leading to cumulative cellular damage, impaired epithelial progenitor activity, and chronic inflammation, which contribute to diseases such as pulmonary fibrosis and chronic obstructive pulmonary disease. Under physiological conditions, lung homeostasis is maintained by epithelial progenitor cells, particularly alveolar type II cells. However, this regenerative capacity is often disrupted in chronic lung diseases, resulting in impaired repair and fibrotic remodeling. Fibroblast growth factors (FGFs) and their receptors (FGFRs) play critical roles in epithelial regeneration, cell survival, and tissue repair. Despite their therapeutic potential, clinical translation remains limited by poor protein stability, rapid proteolytic degradation, low delivery efficiency across biological barriers, and insufficient cell-type specificity due to broad FGFR expression. Recently, several delivery strategies have been evaluated in preclinical lung disease models, including protein engineering, nanoparticle and liposome-based platforms, protein transduction domain- and cell-penetrating peptide-based intracellular delivery, and mesenchymal stem cell-based approaches. Therefore, this review summarizes the roles of FGF signaling in lung regeneration and age-associated diseases, and discusses emerging delivery strategies aimed at bridging the gap between preclinical efficacy and clinical application.
Pericytes are mural cells embedded within the microvascular wall that regulate endothelial stabilization, angiogenesis, and vascular permeability. Once regarded as a relatively uniform vascular support population, pericytes are now recognized as quantitatively and functionally heterogeneous across organs. Neural barrier beds such as brain and retina exhibit high pericyte density and near-continuous mural coverage, whereas peripheral tissues including skeletal muscle display sparse investment. These anatomical differences parallel functional specialization, with central nervous system pericytes exerting strong control over blood-brain barrier (BBB) integrity and transcytosis, while peripheral pericytes participate prominently in vascular remodeling and repair. A critical yet under-integrated dimension of this heterogeneity is developmental origin. Trunk and visceral pericytes arise predominantly from mesodermal progenitors, whereas cranial and forebrain-associated pericytes derive largely from neural crest lineage. This spatial segregation of embryonic origin aligns with vascular specialization, suggesting that lineage contributes to mural regulatory architecture. Stem cell-based comparisons further demonstrate that neural crest-derived pericyte-like cells induce BBB phenotypes more effectively than mesoderm-derived counterparts under identical endothelial conditions, supporting a lineage-linked functional bias. This review integrates anatomical distribution, quantitative investment patterns, molecular signaling mechanisms, and embryonic lineage into a unified framework of pericyte heterogeneity. We propose that developmental origin establishes a regulatory foundation upon which vascular niche signals act, and should therefore be treated as a primary experimental and translational design variable in vascular modeling and regenerative strategies.
Brain organoids have emerged as an important platform for studying human neurodevelopment and neurological disorders, yet their physiological relevance remains limited by the absence of a functional vascular network. Recent efforts therefore focus on developing vascularized brain organoids (vBOs) to better recapitulate neurovascular interactions. Here, we investigate current strategies for vBO engineering, discussing its potential implications such as disease modeling, drug screening, and regenerative therapies along with persistent challenges in reproducing physiologically mature neurovascular features. This review outlines a rapidly evolving framework that enhances neurovascular modeling and supports emerging translational research in neurological disorders.
The CAG expansion in the ataxin-3 (ATXN3) protein is the underlying cause of Spinocerebellar Ataxia Type 3 (SCA3), a polyglutamine disease. The aggregation of mutant ATXN3 protein is hypothesized to contribute to neuronal dysfunction, neurodegeneration, or neuroinflammation. Mesenchymal stem cells have pleiotropic therapeutic properties, and adipose-derived mesenchymal stem cells (ADMSC) have been shown to be safe and well-tolerated in SCA3 patients. In this study, we evaluated the therapeutic effects of ADMSC in SCA3 mice. In a mouse model of SCA3, the Purkinje-cell-specific L7 promoter drives the expression of a truncated form of human ataxin-3 with 69 glutamine repeats. SCA3 mice exhibited cerebellar Purkinje cell degeneration, reduced myelination, and increased gliosis; pathological features also observed in SCA3 patients. SCA3 mice received repeated intravenous administrations of ADMSC, and efficacy was assessed by rotarod performance, molecular and pathological changes, and serum neurofilament light chain (NfL) levels. ADMSC-treated SCA3 mice showed significant improvements in rotarod performance, a reduction in accumulated toxic mutant ATXN3-69Q protein in Purkinje cells, decreased demyelination, and alleviation of neuroinflammatory and systemic inflammatory responses during disease progression. Furthermore, NfL levels, a potential biomarker for SCA3 disease progression, were inversely correlated with the rotarod performance. Based on these findings, we conclude that ADMSC enhance motor function in SCA3 mice by reducing neuroinflammation, demyelination and aggregated mutant ataxin-3 protein levels in Purkinje cells. ADMSC have the potential to serve as a disease-modifying therapy for SCA3 patients.
Partial reprogramming with Yamanaka factors effectively reverses cellular aging but poses potential oncogenic risks, limiting clinical translation. To identify safer rejuvenation induction factors (RIFs), we integrated five aging datasets and compared them with single-cell transcriptomics data from 811 mouse embryonic cells in preimplatation stages. This analysis identified genes exhibiting an inverse relationship between aging (downregulated) and development (upregulated). We further refined this selection by isolating genes common in the intermediate stage of Yamanaka factor-mediated reprogramming. Based on the molecular characteristics of reprogramming factors, we successfully isolated four RIFs associated with ribosome biogenesis, mitochondrial import, translational regulation, and serine metabolism. The expression of these RIFs in aged fibroblasts effectively reduced senescence markers and increased gene expression patterns inversely associated with aging-associated transcriptional change. Unlike the established Yamanaka factors, these identified RIFs modulate development-associated pathways that decline with aging, without activating pluripotency-associated programs, suggesting a potentially safer rejuvenation strategy.
Acute-on-chronic liver failure (ACLF) is a high-mortality syndrome characterized by acute decompensation of liver function. Oxidative stress exerts a pivotal regulatory role in ACLF. Mesenchymal stem cell (MSC)-based therapy is a promising strategy for ACLF, with well-documented safety and efficacy profiles. However, long-term exposure to an oxidative microenvironment can impair MSC regenerative capacity and trigger senescence. Thus, elucidating how the pathological ACLF serum microenvironment affects the biological characteristics of MSCs is important for advancing MSC-based therapeutic strategies. This study investigated the biological alterations of MSCs exposed to ACLF patient serum. We demonstrated that ACLF serum markedly impaired MSC morphology, proliferation, and migration, induced energy metabolism dysfunction, and promoted senescence in vitro. In addition, the levels of advanced oxidation protein products (AOPPs), which are oxidative stress markers, were significantly elevated in the serum of ACLF patients, and this increase was positively correlated with the extent of MSCs senescence. Furthermore, we discovered that ACLF patient serum could lead to elevated intracellular reactive oxygen species (ROS) levels, which in turn drove MSCs senescence. Taken together, these findings suggested that the oxidative microenvironment of ACLF patient serum could alter the functional properties of MSCs and accelerate MSCs senescence through the induction of excessive ROS production. These results help clarify the pivotal role of AOPPs in mediating MSCs senescence and functional impairment, and highlight that monitoring serum AOPPs levels may be a promising biomarker for determining the optimal time window for MSCs transplantation in patients with ACLF.
Neural organoids serve as critical in vitro models for recapitulating the structural and functional complexities of the human nervous system. However, the transition toward high-throughput drug screening and industrial-scale applications is currently hindered by low post-cryopreservation viability. While traditional research focuses on the freeze-thaw cycle itself, the biological mechanisms driving post-thaw failure remain poorly understood. In this study, we identify distinct cellular vulnerabilities during the recovery phase: mature neurons undergo rapid apoptosis, while neural stem cells exhibit a persistent reduction in proliferative capacity, ultimately leading to organoid growth failure. We demonstrate that these damages are closely associated with the induction of reactive oxygen species. Crucially, post-thaw antioxidant treatment significantly mitigates oxidative stress, restoring proliferative potential and substantially increasing overall organoid survival rates. Our findings suggest that shifting the focus from freezing protocols to targeted post-thaw pharmacological recovery represents a superior strategy for ensuring a reliable, scalable supply of neural organoids for biomedical research.
Palatogenesis is tightly regulated at cellular and molecular levels. Cranial neural crest cells (CNCCs), multipotent stem cells that generate most palatal mesenchyme, self-renew, decide fate, and differentiate under cues from their stem cell niche. Orofacial clefts (OFC), among the most common congenital birth defects, arise when CNCC-mediated palate formation is disturbed. Here we review genes, epigenetic machineries, and environmental insults regulating secondary palate development, focusing on CNCC stem cell biology and translational perspectives in tissue engineering, gene therapy, and regenerative medicine for OFC. Canonical signaling pathways regulating palatal shelf proliferation, growth, elevation, and fusion, including Tgf-beta superfamily and Bmp, Fgf, Wnt, and Shh, function as morphogens directing tissue morphogenesis and as regulators of the progenitor niche derived from neural crest cells, balancing proliferation and differentiation. We also overview debated topics such as signaling crosstalk and dissolution of MES. DNA methylation, histone marks, and noncoding RNAs comprise the epigenetic machinery preserving CNCC identity and plasticity. Environmental exposures including smoking, alcohol consumption, and folate deficiency disrupt genetic and epigenetic programs, perturb normal palate development, and elevate OFC risk. Finally, we discuss emerging technologies including single-cell multi-omics, organoids, and CRISPR-based epigenome editing. We propose an integrative conceptual model that places CNCC state transitions at the center of a complex regulatory network. This model emphasizes that disruption at any level, whether arising from niche interactions, epigenetic programming, or environmental exposures, can precipitate cleft palate pathogenesis.
Long-term culture of human pluripotent stem cells (hPSCs) can lead to spontaneous mutations, genomic abnormalities, and alterations in gene expression, thereby compromising their self-renewal and pluripotency. Thus, optimizing the long-term culture conditions of hPSCs is crucial. In this study, we introduce O-cyclic phytosphingosine-1-phosphate (cP1P, Axceso Biopharma Co. Ltd.), a novel culture additive structurally analogous to S1P, which markedly enhances hPSC self-renewal and survival. Our results demonstrate that cP1P supplementation promotes long-term proliferation of hPSCs by upregulating pluripotency markers and maintaining their ability to differentiate into cell types derived from the three germ layers. Furthermore, RNA-seq analysis reveals that cP1P alleviates long-term culture-induced upregulation of apoptosis-and chordate embryonic development-related genes, while preventing the downregulation of stem cell maintenance pathways. Collectively, these findings suggest that cP1P effectively supports the proliferation, pluripotency, and differentiation potential of hPSCs during both short-and long-term cultures.
This study evaluated the therapeutic potential of calcium hydroxylapatite (CaHA) and tonsil-derived mesenchymal stem cells (TMSCs) suspended in hyaluronic acid (HA) for regenerating atrophied vocal fold in a rabbit model of recurrent laryngeal nerve (RLN) injury. Vocal fold atrophy was induced by transecting the unilateral RLN in rabbits. Histological changes in muscle fiber (H&E), cartilage (Safranin O), and collagen deposition (Masson's trichrome), were assessed at 8, 12, 16, and 26 weeks post-injury to confirm the establishment of vocal fold atrophy model. CaHA or TMSC＋HA was injected into the atrophied vocal folds. After 8 weeks, laryngeal tissues were harvested to evaluate tissue morphology and the engraftment of transplanted cells using histological staining (H&E, Safranin O, Masson's trichrome, Alizarin Red S) and immunofluorescence analysis for human mitochondria. At 8 weeks after RLN transection, CaHA injection-maintained medialization of the atrophied vocal fold but failed to promote tissue regeneration and induced localized foreign body reaction characterized by multinucleated giant cells and granular calcium deposit. In contrast, TMSC＋HA injection markedly enhanced muscle fiber regeneration, reduced interstitial spaces between muscle fibers, and did not form fibrous capsule. Moreover, TMSC＋HA did not elicit immune reactivity or tissue calcification, suggesting superior biocompatibility and tissue integration. These findings indicate that while CaHA acts as a durable filler regenerating potential, TMSC＋HA offers distinct advantages by promoting muscle regeneration, and extracellular matrix remodeling. TMSC＋HA hydrogel presents a promising regenerative strategy for restoring atrophied vocal folds following RLN injury, demonstrating excellent biocompatibility and effective tissue integration.
Huntington's disease (HD) is characterized by progressive striatal degeneration associated with mutant huntingtin (mHTT)-related proteostatic disruption and chronic neuroinflammation. Although mHTT-lowering approaches hold therapeutic promise, their capacity to restore the degenerating neural microenvironment remains limited. Here, we evaluated the therapeutic potential of human induced pluripotent stem cell (iPSC)-derived neural precursor cells (s513-NPCs) in two complementary HD models, the acute R6/2 transgenic fragment model and the protracted, full-length YAC128 genomic model. Intrastriatal transplantation of s513-NPCs resulted in sustained functional improvement, including stabilization of motor coordination and attenuation of neuromuscular decline, across both disease contexts. These neuroprotective effects were accompanied by efficient donor cell engraftment and integration within the host striatum. At the molecular level, transplantation was associated with coordinated changes in proteostasis-related pathways, reflected by reduced mHTT aggregate burden and modulation of proteasomal and autophagic markers. In parallel, enhanced local BDNF-TrkB signaling was observed in grafted regions, consistent with improved neuronal support. Notably, transplanted NPCs exhibited context-dependent immunological responses, characterized by attenuation of pro-inflammatory signatures in aggressive disease stages and features of a reparative microenvironment in more protracted settings. Collectively, these findings demonstrate that iPSC-derived neural precursor transplantation confers robust neuroprotective effects in HD models, supporting its potential as a stem cell-based strategy to mitigate striatal pathology and functional decline.
Preterm premature rupture of membranes (PPROM) is a major cause of preterm birth and neonatal morbidity, with no established treatment to restore membrane integrity. Mesenchymal stem cells (MSCs), known for their regenerative and immunomodulatory properties, harbor promising therapeutic potential for fetal membranes repair. This study aimed to evaluate the rapid barrier reinforcement effect of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) using in vitro and ex vivo models of PPROM. A wound healing assay was conducted to assess the effect of WJ-MSCs on human amniotic epithelial cells proliferation and migration. An ex vivo PPROM model was established using incised human fetal membranes to simulate membrane rupture. WJ-MSCs were directly applied to the lesion site at varying doses. Therapeutic efficacy was evaluated by a leak test and histological analysis. WJ-MSCs and their conditioned medium significantly enhanced epithelial wound closure in vitro, demonstrating that soluble paracrine factors secreted by WJ-MSCs have the potential to aid membrane injury restoration. In the ex vivo PPROM model, WJ-MSCs treatment reduced both leakage area and frequency of fetal membranes, with the most significant effect observed at a medium dose (5.0×105 cells). Histological evaluations revealed partial recovery of the fetal membranes, particularly the chorion layer. These findings suggest that WJ-MSCs contribute to rapid barrier reinforcement of injured fetal membranes. Taken together, WJ-MSCs enhance epithelial healing and support restoration of membrane integrity, highlighting their potential as a therapeutic approach for PPROM. Further, in vivo studies are required to confirm therapeutic efficacy and evaluate safety.
Arts syndrome is a rare X-linked recessive neurodevelopmental disorder arising from pathogenic variants in PRPS1, which encodes phosphoribosyl pyrophosphate synthetase 1-an enzyme essential for de novo nucleotide biosynthesis. Affected individuals typically exhibit sensorineural hearing loss, intellectual disability, cerebellar ataxia, and recurrent infections. However, despite the severity of these clinical manifestations, therapeutic interventions remain limited, largely due to an incomplete understanding of the cellular pathophysiology underlying the disorder. In this study, we generated patient-specific induced pluripotent stem cells harboring the PRPS1 p.V42L variant and differentiated them into neural stem cells (NSCs) and neurons to elucidate disease mechanisms and explore potential therapeutic strategies. Patient-derived NSCs demonstrated significantly reduced proliferative capacity, aberrant nuclear morphology, and increased neuronal senescence, while mitochondrial integrity and function were largely preserved. Neurons differentiated from these NSCs exhibited impaired neurite outgrowth and reduced branching complexity, indicative of disrupted neurodevelopmental processes. Notably, supplementation with nicotinamide mononucleotide, a precursor of nicotinamide adenine dinucleotide (NAD＋), partially ameliorated defects in NSC proliferation, nuclear architecture, and neuronal morphology. Collectively, these findings delineate key cellular mechanisms underlying PRPS1-associated neurodevelopmental pathology and identify NAD＋ metabolic augmentation as a promising therapeutic avenue for Arts syndrome and related PRPS1-mediated disorders.
As global societies age, the prevalence of neurodegenerative disorders, such as Alzheimer's disease, is rapidly increasing, intensifying the need to understand the mechanisms of aging and their contribution to these conditions. Consequently, the focus of aging research has shifted from the traditional concept of chronological age to a more nuanced understanding of biological age. This has spurred active investigation into robust biomarkers, including cellular senescence. However, the application of classical senescence markers to the brain presents a substantial challenge, as their validity in post-mitotic cells, such as neurons, remains unclear. In this review, we highlight the limitations of the current metrics for cellular senescence as indicators of biological aging, and propose a path forward focused on identifying and modeling cell-type-specific aging markers within the brain.
Human pluripotent stem cells (hPSCs) can self-renew indefinitely and differentiate into all three germ layers. However, the primary regulators of hPSC cell cycle dynamics remain unclear. To identify novel regulators of hPSC proliferation, transcriptomic profiling of undifferentiated hPSCs and somatic cells was performed via next-generation sequencing. Stomatin-like protein 2 (STOML2) and prohibitin (PHB) were among the upregulated genes in hPSCs and were closely associated with the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway. Temporal expression analysis indicated that STOML2 and PHB decreased during differentiation and increased during reprogramming. Short hairpin RNA (shRNA)-mediated knockdown of STOML2 in hPSCs caused phenotypic changes. Gene expression analyses demonstrated reduced OCT4, NANOG, PHB, and phosphorylated ERK, alongside increased differentiation markers across all three germ layers. The STOML2-PHB axis is essential for maintaining hPSC identity by sustaining ERK/MAPK activity and cell cycle structure. This study identified STOML2 as a key pluripotency regulator and provides new insight into intrinsic stem cell fate control.
Cardiotoxicity assessment is a crucial step in the drug development process. With growing interest in alternatives to animal testing, preclinical cardiotoxicity evaluation has become increasingly important. Human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) offer a physiologically relevant in vitro model for this purpose. As a result, electrophysiological analysis platforms using iPSC-CMs have gained attention. However, conventional microelectrode array (MEA) chips rely on metal electrodes, which are costly and optically opaque. This lack of transparency limits detailed morphological observation of the cells. In this study, we employed an MEA chip incorporating transparent and conductive indium tin oxide (ITO) electrodes to simultaneously monitor both morphological changes and field potential (FP) of iPSC-CMs. iPSC-CMs cultured on ITO chips exhibited stable electrophysiological signals reflecting coupled depolarization and repolarization, along with self-organization. Short-term exposure to ion channel blockers did not induce noticeable morphological alterations; however, dose-dependent changes in FPs were observed. In contrast, treatment with cardiotoxic drugs resulted in morphological damage and reduced cell viability, accompanied by progressive alterations in key FP parameters over the treatment period. These findings demonstrate the potential of ITO-based MEA as next-generation cardiotoxicity evaluation platforms capable of real-time monitoring of both drug-induced electrophysiological responses and optical cellular changes.
Pyrene (Pyr), a representative subtype of polycyclic aromatic hydrocarbons, is primarily generated during the incomplete combustion of organic matter. As an environmental pollutant, Pyr has been reported to exert adverse effects on various physiological systems. However, data regarding its cardiotoxicity remain limited. In this study, we investigated the acute cardiotoxic effects of Pyr using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). hiPSC-CMs were exposed to various doses of Pyr, and both cell viability and functional parameters were evaluated. Pyr did not affect cell viability under 30-minute and 2-hour exposure conditions regardless of dose. However, significant differences were observed in the dual-cardiotoxicity evaluation based on a microelectrode array, which allows simultaneous assessment of electrophysiological signals and contractility in CMs. Pyr decreased beat period and field potential duration in a dose-dependent manner, resembling the acute cardiotoxicity pattern of IKr and ICaL channel blockers, and progressively reduced spike amplitude over time. Although a transient decrease in beat amplitude was observed at high dose, it recovered over time, while the excitation-contraction delay was reduced. Taken together, these findings demonstrate that Pyr can induce functional cardiotoxicity even under acute exposure and highlight the value of the established evaluation method for the development of safer alternative substances.
Human chemically derived hepatic progenitors (hCdHs) reprogrammed using three chemicals-HGF, A83-01, and CHIR99021 (collectively denoted as "HAC")-have been suggested as a novel therapeutic for patients with severe liver diseases in our previous study. Despite its high proliferation and re-differentiation ability into functional hepatocytes, the reprogramming mechanism of hCdHs remained unknown. Recently, it has been reported that autophagy, a self-degradation process, is responsible for stem cell metabolism. In this study, we investigated whether autophagy regulates the generation mechanism of CdHs, mainly using hepatocytes from C57BL/6 mice, with additional analysis using human hepatocytes. As a result, we found that autophagy flux is inhibited during the generation of mouse CdHs (mCdHs) by A83-01, which is compensated by CHIR99021. Moreover, the suppression of autophagy by bafilomycin A1 enhanced the proliferation ability of mCdHs during the generation process. hCdHs also showed a similar autophagy inhibition pattern to mCdHs during the generation process. Taken together, our study indicates that autophagy is downregulated during the generation of CdHs, promoting their proliferation. This may contribute to the production of hCdHs with stable productivity, which may serve as a therapeutic for severe liver diseases.
