Regenerative medicine, and in particular cell-based therapies, are under investigation as therapeutics in the management of inflammatory bowel disease, where despite significant advancements in management, prolonged remission is achieved in less than half of patients experiencing these disorders. In contrast to conventional immunomodulatory medications, these therapies are hypothesised to act through multiple pathways including via regenerative mechanisms, which may enable them to break through the current therapeutic ceiling. Potential therapy candidates include mesenchymal stem cells, human amnion epithelial cells, and regulatory T-cells, as well as their derivatives including extracellular vesicles. Extensive preclinical studies have demonstrated the multi-modal nature of these therapies as well as shared and unique properties. Controversy remains regarding contradictory study outcomes and the efficacy of regenerative therapies in human trials. In this narrative review, we first examine the mechanisms of these candidate cell therapies, including signalling via cytokines and extracellular vesicles, and interactions with immune cells, stromal cells, and the microbiome to determine differences and similarities between them. The second part delves into the current state of regenerative and cell-based therapy, focusing on mesenchymal stem cell, human amnion epithelial cell, T regulatory cells, and their respective extracellular vesicles in IBD treatment. Finally, we close by identifying the major literature gaps and barriers to bringing regenerative medicines to clinical use, resulting in recommendations for future research.

Skin aging, photoaging, and chronic wounds are increasingly recognized to be driven by mitochondria-centered mechanisms characterized by oxidative stress, defective mitophagy, and impaired bioenergetics in cutaneous cells. Autologous biologics, including platelet-rich plasma, stromal vascular fraction, bone marrow aspirate concentrate, and mesenchymal stromal/stem cell-derived products, are widely used for skin rejuvenation and wound repair. Recent studies have suggested that many of these effects are mediated by mitochondrial mechanisms, including metabolic reprogramming, redox modulation, and intercellular mitochondrial transfer. Concurrently, biophysical modalities such as red/near-infrared photobiomodulation (PBM), low-intensity pulsed ultrasound, mechanical stimulation, and nanoengineered cues can modulate mitochondrial function in skin-relevant cells. In this review, we integrate these lines of evidence to introduce the concept of mitochondria-targeted biophysical priming of autologous biologics for dermatological applications. We summarize the mitochondrial biology in skin pathology, evaluate these biologics as mitochondria-active therapies, and outline ex vivo priming implementation using PBM, ultrasound, or mechanical stimulation. Finally, we discuss key regulatory considerations that support clinical translation.

Short bowel syndrome (SBS) develops when the remaining intestine is unable to sustain adequate nutrient and electrolyte absorption following extensive bowel resection. The condition is characterized by malabsorption and significant fluid losses which lead to dehydration and progressive weight loss, thus promoting patient dependence on parenteral fluids or nutrition. After an initial acute phase marked by accelerated intestinal transit and gastric hypersecretion, long-term clinical outcomes are largely determined by the capacity of the remaining bowel for intestinal adaptation-a sustained process of structural, functional, and molecular remodeling that enhances absorptive efficiency and restores fluid and nutrient homeostasis. This review summarizes the key histological and cellular features of the adaptive response, including crypt and villus remodeling, mucosal hyperplasia, and smooth muscle hypertrophy, and integrates emerging concepts in crypt biology that define the dynamic cross-talk between intestinal stem cells and the mesenchymal niche, together with their upstream regulatory pathways.

Background: The individual and social burden of endometriosis is high, and the diagnosis is usually delayed by 7-10 years. Menstrual effluent (ME) represents an accessible and uniquely informative biofluid. This systematic review evaluated the pathophysiological relevance and diagnostic potential of ME in endometriosis. Methods: Following PRISMA 2020 guidelines, we systematically searched PubMed/MEDLINE, EBSCOhost (Academic Search Premier, APA PsycArticles, APA PsycInfo, CINAHL, and MEDLINE), Semantic Scholar, and Google Scholar from inception to 30 November 2025. Original studies analyzing human ME or ME-derived cells in women with endometriosis versus controls were eligible. We extracted study design, analytic methods, diagnostic accuracy metrics (AUC, sensitivity, and specificity), mechanistic pathways, and risk of bias (QUADAS-2 for diagnostic, and NIH tools for mechanistic studies). Results: Thirty-five studies were included. ME consistently captured key pathophysiological mechanisms of endometriosis, including impaired decidualization and progesterone resistance, immune dysregulation with diminished cytotoxic clearance, pro-angiogenic and invasive phenotypes, heightened stem/progenitor cell survival, cellular senescence and DNA damage, and altered extracellular-vesicle signaling. Diagnostic accuracy was reported in nine studies. Aromatase mRNA showed the highest performance (AUC 0.977), followed by TGF-β1 (AUC 0.973) and IGFBP1 (AUC 0.92). A lipidomic two-marker model achieved an AUC of 0.87. All diagnostic assessments were based on case-control studies; none conducted prospective validation. Conclusions: ME is a biologically relevant, non-invasive, and patient-acceptable biospecimen reflecting core endometriosis mechanisms and yielding promising diagnostic accuracy. The highest diagnostic performance was achieved for assays reflecting steroidogenic and growth-factor pathways (e.g., aromatase and TGF-β1). Standardization and prospective validation are needed before clinical adoption.

Articular cartilage, a highly specialised and avascular tissue, exhibits limited regenerative potential following trauma or degenerative conditions such as osteoarthritis (OA). Conventional surgical interventions, including microfracture and autologous chondrocyte implantation (ACI), have shown limited long-term efficacy due to donor site morbidity and restricted cell proliferation. In this context, mesenchymal stromal cells (MSCs) have emerged as a promising alternative owing to their multipotency, self-renewal capacity, and low immunogenicity. While bone marrow (BM) remains the traditional source of MSCs, recent studies have reported that peripheral blood-derived mesenchymal stromal cells (PB-MSCs) may possess chondrogenic, osteogenic, and adipogenic potential comparable to that of BM-derived MSCs. PB-MSCs can be harvested through minimally invasive methods, thereby avoiding the complications associated with BM aspiration. Experimental evidence indicates that PB-MSCs exhibit strong cell viability, proliferative potential, and the ability to synthesise cartilage-specific extracellular matrix proteins, such as type II collagen and sulphated glycosaminoglycans, within three-dimensional scaffolds. Immunophenotypically, PB-MSCs express mesenchymal markers including CD29, CD44, CD90, and CD105 while lacking hematopoietic markers CD34 and CD45. Flow cytometry analyses reveal that CD105+ populations increase following cryopreservation, highlighting their clinical utility. In contrast to these experimentally defined PB-MSCs, the term peripheral blood stem cells (PBSCs) is used in clinical studies to describe heterogeneous, non-cultured peripheral blood-derived cell preparations, typically enriched in hematopoietic stem and progenitor cells following granulocyte colony-stimulating factor (G-CSF) mobilisation, without full mesenchymal characterisation. In vitro studies confirm successful tri-lineage differentiation, whereas in vivo investigations have demonstrated effective cartilage regeneration using PB-based clinical approaches, including postoperative intra-articular administration of hyaluronic acid (HA) combined with PBSCs, as well as implantation of PBSCs covered with a collagen membrane. Furthermore, advancements in biomaterial engineering, such as poly(ethylene glycol)-cysteine-arginine-glycine-aspartic acid (PEG-CRGD) hydrogels, have enhanced PB-MSC adhesion, proliferation, and chondrogenic differentiation while promoting immunomodulation through M2 macrophage polarisation. Despite these promising outcomes, the available evidence remains limited and heterogeneous, with substantial variability in cell definitions, experimental models, and clinical study designs, which currently constrains definitive conclusions regarding clinical efficacy. Future research should focus on optimising isolation protocols, understanding molecular pathways governing PB-MSC chondrogenesis, and standardising clinical applications. Overall, PB-MSCs represent a viable, less invasive, and translationally relevant cell source for cartilage regeneration and regenerative orthopaedic therapies.

Background. NOTCH receptors play a pivotal role in carcinogenesis. Upon ligand binding, a cascade of proteolytic cleavages mediated by ADAM proteases and the γ-secretase complex activates the receptor, ultimately releasing the NOTCH intracellular domain (NICD). NICD translocates to the nucleus, where it regulates gene expression. This review mainly aims to evaluate γ-secretase inhibitors (GSIs) as anticancer agents in preclinical and clinical settings, with a focus on their ability to block tumor progression, target cancer stem cells, and overcome resistance to standard therapies. Methods. A systematic search was conducted in the ISI Web of Science, PubMed, and Scopus databases, following PRISMA guidelines. The review included preclinical in vitro and in vivo studies, as well as clinical trials, investigating GSIs, either as monotherapy or in combination with other treatments, in TNBC, metastatic melanoma, PDAC, gastric cancer, and NSCLC. Exclusion criteria included duplicates, non-English articles, studies published before 2010, studies on non-cancer conditions, research unrelated to NOTCH signaling, and studies outside the selected cancer types. Overall, 69 articles were included and categorized into the five types of cancer analyzed (20 on NSCLC, 22 on TNBC, 11 on metastatic melanoma, 7 on GC, and 9 on PDAC). Of these, 60 studies corresponded to preclinical research in the types of cancer, and 9 studies corresponded to clinical trials in the types of cancer except for GC. Two independent authors screened and extracted relevant data, with disagreements resolved by the corresponding author. Findings were synthesized qualitatively across cancer types under study. Results. This review summarizes therapeutic advances involving GSIs in cancers driven by oncogenic NOTCH signaling, based on the 69 articles included. Preclinical studies show that GSIs synergize with chemotherapy and radiotherapy, particularly in NSCLC, melanoma, and TNBC, and block EMT, overcome therapeutic resistance, and improve prognosis. Commonly used GSIs include DAPT and RO4929097, which enhance the efficacy of agents, such as gemcitabine (PDAC), paclitaxel, osimertinib, erlotinib, and crizotinib (NSCLC), and 5-FU (gastric cancer, TNBC). Promising strategies include combining GSIs with SAHA, ATRA, CB-103, and other NOTCH signaling targeting molecules, either alone or with chemo- and radiotherapy. Clinical trials with GSIs, however, remain limited. RO4929097 is the most extensively tested GSI in clinical settings. PDAC trials combining GSIs with gemcitabine showed no benefit; melanoma trials yielded modest outcomes; and TNBC trials demonstrated partial responses to GSIs but overall low efficacy and significant adverse events. Discussion and Conclusions. Despite encouraging preclinical evidence, clinical trials with GSIs have underperformed, largely due to tumor heterogeneity, dosing limitations, and the non-selective nature of γ-secretase inhibition. Other NOTCH inhibitors, such as DLL4 antibodies, also resulted in partial responses and secondary effects. Future strategies should prioritize receptor-specific NOTCH inhibitors, patient stratification based on NOTCH pathway activation, and optimized combination regimens. Emerging approaches include integrating immunotherapy with advanced technologies such as CRISPR, CAR-T cells, and bispecific antibodies, as well as targeted delivery systems to enhance efficacy and reduce toxicity. Additional research directions include addressing the tumor microenvironment and EMT-driven resistance, elucidating the mechanisms of immune evasion, and inhibiting tumor angiogenesis. Finally, leveraging artificial intelligence and big-data-driven personalized medicine, including sex-specific considerations, will be essential for improving patient outcomes.

Skeletal muscle regeneration declines with age despite the persistence of satellite cells (muscle stem cells, MuSCs), suggesting that regenerative impairment reflects functional dysregulation rather than MuSC depletion. Increasing evidence identifies early MuSC activation during the immediate post-injury period as a stress-sensitive, rate-limiting transition that is particularly vulnerable in aged muscle. Aged MuSCs exhibit elevated stress responses and reduced membrane remodeling capacity, accompanied by weakened activation-associated transcriptional induction. In contrast, proliferative and differentiation programs remain largely intact once activation is successfully initiated. These findings underscore that impaired coordination during early activation contributes to long-term regenerative decline in aging. Within this framework, MG53 (tripartite motif-containing protein 72, TRIM72), a muscle-enriched TRIM family E3 ubiquitin ligase originally identified as a mediator of sarcolemmal membrane repair, may also function as a stress-responsive regulator that stabilizes the early activation environment. Rather than directly determining cell fate, MG53 is proposed to facilitate activation by mitigating stress-associated membrane disruption and maintaining programmatic coordination under age-related physiological constraints. Most mechanistic evidence derives from rodent models, and direct validation in human aging muscle remains limited. These observations suggest that targeting early activation, rather than simply increasing proliferation, may better preserve regenerative capacity in aging skeletal muscle.

Perinatal brain injury (PBI) is a leading cause of long-term neurological deficits in newborns, yet effective therapies are limited. At the cellular level, PBI involves hypoxic-ischemic stress, neuroinflammation, oxidative damage, excitotoxicity, and disrupted neurovascular and glial development. Traditional animal models and 2D cultures cannot fully capture the spatiotemporal complexity of the developing human brain, highlighting the need for more physiologically relevant systems. Human brain organoids have emerged as advanced three-dimensional models that recapitulate region-specific cytoarchitecture, neuronal and glial differentiation, and early circuit formation. They enable modeling of hypoxic-ischemic and inflammatory insults, allowing for the study of injury-induced changes in neurogenesis, gliogenesis, synaptic development, and cell interactions. Organoids facilitate identification of molecular pathways involved in injury and repair, supporting therapeutic target discovery. Using patient-derived induced pluripotent stem cells, organoids also allow personalized pharmacogenomic studies to assess genotype-dependent drug responses and toxicity. Despite limitations such as variability, lack of vascularization and immune components, and ethical considerations, brain organoids offer a promising platform to bridge developmental neurobiology and translational therapeutics, paving the way for targeted and individualized interventions in PBI.

Stem cell therapy represents an intrinsic part of regenerative medicine, with expanding applications in orthopedic and musculoskeletal research. Although studies span from small-animal models to early-phase clinical trials, the field remains fragmented, with wide variation in stem cell types, delivery methods, and target tissues. A consolidated overview is needed to inform future directions and bridge the gap between preclinical promise and clinical application. This scoping review synthesized evidence from 500 preclinical and clinical studies, identified through systematic searches and screened in accordance with PRISMA-ScR guidelines. Data were extracted on stem cell type and source, delivery approach, targeted tissue and organ, and disease indication. We found that autologous bone marrow-derived mesenchymal stem cells were the most used, with adipose- and perinatal-derived cells gaining prominence in recent years. Small-animal models such as rats and rabbits predominated, while large-animal and human studies focused mainly on knee osteoarthritis. Intra-articular injection was the principal delivery method across both preclinical and clinical settings. By mapping prevailing practices and emerging trends, this review provides a comprehensive reference for researchers, clinicians, and regulatory stakeholders. It highlights translational pathways, identifies critical gaps, and offers evidence to guide the design of safe, effective, and scalable regenerative therapies in orthopedics.

The development of the esophagus and trachea following the septation of the anterior foregut is a highly regulated process involving bidirectional communication between the endoderm and mesoderm. Signaling pathways such as the Bone Morphogenetic Protein family, Wnt/β-catenin, Sonic Hedgehog, and Fibroblast Growth Factor family mediate this complex crosstalk to induce the dorsal-ventral patterning of the anterior foregut as well as lineage specification. Even though the mechanisms are not fully understood, dysregulation of signaling pathways may lead to congenital malformations such as tracheomalacia, laryngeal-tracheal clefts and multiple types of esophageal atresia with/without tracheoesophageal fistula (EA/TEF). Human induced pluripotent stem cells (iPSCs) provide a robust in vitro platform to monitor the normal and abnormal development of esophagus and trachea and to understand the roles of the endoderm and mesoderm during anterior foregut development. Recent studies have demonstrated that direct differentiation of iPSCs into epithelial and mesenchymal lineages can recapitulate the key stages of foregut development. In this regard, in the current paper, we review the signaling pathways involved in the development of organs deriving from the anterior foregut as well as the roles of the endoderm and mesoderm revealed by previous studies. Furthermore, we discuss the use of iPSCs as a valuable model for investigating the bidirectional communications between the endoderm and mesoderm, which can broaden our knowledge and understanding of the critical mechanisms leading to normal and abnormal development of the esophagus and trachea.

Neutrophil extracellular traps (NETs) are web-like DNA-protein structures released by activated neutrophils. Initially recognized for their antimicrobial roles, NETs are now known to drive sterile inflammation, thrombosis, and tissue remodeling. This review highlights their involvement in key pancreatic diseases, including acute pancreatitis (AP) and pancreatic ductal adenocarcinoma (PDAC). In AP, early NET formation correlates with disease severity and septic complications, contributing to acinar injury, microvascular thrombosis, ductal obstruction, and organ dysfunction. In PDAC, NETs shape a fibrotic and immune-resistant tumor microenvironment by promoting stromal activation, immune exclusion, metastasis, and hypercoagulability. Tumor- and stroma-derived signals sustain NET formation within this niche. We also discuss NET-related biomarkers for risk assessment and therapy monitoring, and explore therapeutic strategies that target NETs-ranging from their degradation with DNase to their inhibition of upstream pathways such as PAD4, autophagy, and oxidative signaling. Targeting NETs may also reduce their downstream effects on thrombosis and immune suppression. Overall, NETs emerge as critical drivers of pancreatic disease progression and represent promising therapeutic targets.

Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults. Emerging evidence endorses that gut dysbiosis contributes to GBM progression through the gut-brain axis (GBA), promoting inflammation and therapeutic resistance via abnormal short-chain fatty acid production and cytokine dysregulation. Exosomes, naturally occurring nanovesicles (30-150 nm), offer promising therapeutic potential due to their blood-brain barrier permeability, biocompatibility, and versatile cargo capacity. This review examines exosome engineering strategies for dual targeting: inhibiting alterations in gut microbiome and inducing regulated cell death mechanisms such as apoptosis and ferroptosis in GBM. We describe exosome engineering with detailed focus on cargo loading approaches (e.g., genetic modification, electroporation, and sonication), exosome surface functionalization with specific ligands (e.g., antibodies), and exosome biogenesis pathway manipulation. Engineered exosomes can deliver anti-inflammatory agents and gut microbiome modulators to restore GBA homeostasis while simultaneously transporting tumor-suppressive non-coding RNAs (e.g., miRNAs, siRNAs) and therapeutic agents to induce apoptosis by overcoming temozolomide resistance, and trigger ferroptosis-inducing components in GBM stem cells. Preclinical studies make obvious that this dual-targeting approach ought to enhance therapeutic efficacy by creating systemic immunity and eliminating tumor cells. However, clinical translation brings forth challenges, such as manufacturing, targeting specificity, and standardized quality control, and warrants further study.

Cancer stem cells (CSCs) are increasingly recognized as central drivers of tumorigenesis, therapeutic resistance, and recurrence across diverse malignancies. This review synthesizes our current understanding of CSC biology across CNS tumors, with a focus on glioblastoma, where stem-like cells are sustained by specialized and overlapping tumor microenvironmental niches. Perivascular, hypoxic, invasive, immunosuppressive, and extracellular matrix-associated niches cooperatively enforce stemness, metabolic adaptability, immune evasion, and phenotypic plasticity, enabling CSC persistence despite maximal surgical resection and standard-of-care therapy. Notably, CSCs extend beyond radiographically defined tumor margins and populate peritumoral regions, providing a biological basis for near-universal recurrence. Advances in multiparametric imaging, stem cell-based ex vivo and in vivo models, and single-cell and spatial profiling have refined insight into CSC heterogeneity, niche dependence, and treatment resistance. Together, these findings reframe therapeutic strategies, highlighting the need for function-preserving maximal resection and multimodal therapies that target both CSC-intrinsic pathways and their supportive microenvironments.

Innate-like T cells (ILTCs) link innate immune responses with adaptive immune functions. This group includes invariant natural killer T (iNKT) cells, mucosa-associated invariant T (MAIT) cells, and γδ T cells. ILTCs detect transformed or stressed cells via non-classical antigen presentation pathways. For example, iNKT cells recognize CD1d-presented glycolipids, MAIT cells respond to MR1-presented metabolites from riboflavin pathways, and γδ T cells sense phosphoantigens through butyrophilin-dependent mechanisms and stress ligands. These features support early tumor control and shape downstream immunity by promoting dendritic cell activation, NK cell function, and priming of tumor-reactive CD8+ T cells. In established tumors, ILTC activity is frequently suppressed. Reduced antigen presentation, inhibitory cytokines, hypoxia, and metabolic constraints, including lactate accumulation and kynurenine production, limit effector responses and promote hyporesponsive states. Transcriptional regulators such as TOX, NR4A family members, and BATF are associated with these programs. This review discusses ILTC roles in tumor surveillance, immune escape, and therapeutic strategies to restore their function.

Is it reasonable to use allogeneic mesenchymal stem cells (MSCs) therapy for thin endometrium and recurrent implantation failure? Thin endometrium (TE) and recurrent implantation failure (RIF) are associated with poor reproductive outcomes. Single-cell RNA sequencing (scRNA-seq) shows that such pathologies involve functional impairment of endometrial stromal, vascular, immune cells rather than reductions in cell numbers. MSCs exert regenerative and immunomodulatory effects and are proposed as candidates for endometrial repair. scRNA-seq studies indicate that TE and RIF are characterized by stromal progenitor dysfunction, impaired angiogenesis, immune dysregulation, and cellular senescence, providing a biological rationale for investigating allogeneic MSC-based therapies. scRNA-seq studies of human endometrium in patients with TE and RIF are reviewed alongside experimental and clinical studies evaluating autologous and allogeneic MSCs, with particular emphasis on umbilical cord-derived MSCs. Transcriptomic analyses consistently demonstrate reduced proliferation and decidualization of endometrial stromal cells, suppression of angiogenesis, immune dysregulation, and activation of senescence-associated genes. Preclinical studies show that MSC administration restores endometrial structure, vascularization, and receptivity markers. Early clinical studies suggest potential benefit, although data remain limited and heterogeneous due to non-randomized studies. Allogeneic MSCs are promising as therapy, but further studies on mechanisms and clinical validation are needed.

Glioblastoma stem cells (GSCs) function as dynamic regulators of tumor persistence, maintained by interconnected genetic, epigenetic, metabolic, and microenvironment-derived circuits. Rather than fixed entities, GSCs continuously recalibrate their functional state as transcriptional regulators, chromatin architecture, and non-coding RNA networks shift in response to microenvironmental cues. Hypoxic, vascular, and immune niches reinforce these adaptive states by stabilizing HIF signaling, modulating cytokine gradients, and sustaining immunosuppression. Metabolic flexibility further supports survival under therapeutic and environmental stress. Standard therapies inadvertently activate these same resilience pathways: TMZ enhances DNA repair and quiescent survival, while radiation promotes mesenchymal transition and immune evasion, thereby enriching GSC-associated circuits that drive recurrence. Understanding how these molecular circuits converge to sustain stemness, plasticity, and microenvironmental crosstalk highlights the need for combinatorial strategies that simultaneously disrupt epigenetic gating, metabolic rewiring, ncRNA-controlled repair, and niche-dependent signaling to achieve durable glioblastoma control.

Hair loss, or alopecia, constitutes a significant and prevalent concern affecting individuals worldwide. Despite the availability of numerous commercial solutions, many individuals continue to experience substantial psychological distress, leading to adverse impact on personal relationships, social interactions, and occupational performance. The limitations of conventional treatments, such as oral medication with potential systemic side effects and topical applications with localized adverse events, have driven the exploration of alternative therapies. Emerging localized injectable treatments for hair regrowth (PRP, stem cells, exosomes) offer a promising avenue for addressing this persistent issue. These injectable therapies hold the potential to minimize the systemic side effects often associated with oral medications, while also mitigating the localized adverse events that can arise from topical applications. This narrative review provides a comprehensive overview of the medical state-of-the-art in off-label injectable hair regrowth treatments, delving into the diverse range of available options. A critical component of this narrative review involves a thorough evaluation of relevant clinical studies, assessing the efficacy and safety profiles of these emerging therapies. Furthermore, detailed attention is given to injection techniques and administration protocols, crucial factors in optimizing treatment outcomes. These evolving therapies represent a significant advancement in the field of scalp regenerative medicine. By stimulating hair follicle reactivation, these treatments aim to promote sustained and natural hair growth, providing individuals with more effective and durable solutions. The enhanced safety profiles of these injectable therapies, compared to conventional systemic pharmacological treatments (minoxidil, finasteride), offer a substantial improvement in patient care, addressing a widespread clinical need.

Organoids are derived from pluripotent stem cells or tissue stem cells, progenitor cells, or differentiated cells from healthy or diseased tissues (e.g., tumors). Numerous organoid engineering strategies have been tested to support the culture, growth, proliferation, differentiation, and maturation of organoids. A variety of organoids and organoid-on-chips have also been constructed to reflect real environments of human and mouse organs. Currently, four major areas of potential application for organoids include disease modeling, anticancer drug screening, drug toxicology testing, and gene/cell therapy. For cancer immunotherapy, immune organoids based on co-culturing human tumor cells have been used as a critical platform for drug screening and targeted therapy. This review summarizes recent advances in organoid culture, lists the methods for constructing organoids and their main applications, and highlights its value as a tool for precise cancer modeling. Given the enormous potential of organoids as an in vitro culture model in cancer treatment, we also discussed organoid-based methods for angiogenesis and immune microenvironment modeling, and analyzed the wide range of applications of immune organoids, such as testing treatment response, exploring mechanisms of drug resistance, optimizing treatment strategies, and guiding drug development. Finally, we attempt to look into the critical challenges and bright prospects for cancer organoid research.

Polyploid giant cancer cells (PGCCs) are the major driver of tumor recurrence, drug resistance, stemness, and are a significant obstacle in cancer therapy. These highly unstable cells form via mitotic slippage, failed cytokinesis, or cell fusion, and are implicated in chemotherapy-induced senescence. The survival and proliferation of PGCCs are critically dependent on altered mitochondrial dynamics and physiology, which includes a shift towards hyperfusion and asymmetric fission. PGCCs possess a higher mitochondrial content, indicating increased biogenesis to support their high metabolic demand, which is often met through glycolysis. After chemotherapy, these cells can bypass senescence to produce aggressive, proliferative progeny with enhanced stemness. This review documents the profound link between mitochondrial dynamics and the formation of PGCCs, their acquired drug resistance, and ability to drive tumor relapse. We propose that targeting mitochondrial dynamics and physiology offers a promising therapeutic strategy to combat PGCCs, providing a novel approach for next-generation personalized and precision cancer care.

Sporadic form of Alzheimer's disease (sAD), remains a complex neurodegenerative disorder with limited translational models. Brain organoids derived from human induced pluripotent stem cells (hiPSCs) have emerged as promising tools to recapitulate aspects of human brain development and pathology. Recent advances have introduced vascularized, immune-competent organoids capable of modeling hallmark features of sAD, including amyloid-β accumulation, tau pathology, and neuroinflammation. New strategies to enhance organoid maturation, cellular diversity, and aging phenotypes are pushing the boundaries of disease modeling. This review highlights cutting-edge developments in brain organoid systems for studying sAD, addresses key limitations, and outlines future directions to improve their translational relevance for therapy and mechanistic insights.