Cell TransplantationPub Date : 2026-01-01Epub Date: 2026-03-11DOI: 10.1177/09636897261427908
Vladislav Volarevic, Carl Randall Harrell, Crissy Fellabaum, Valentin Djonov, Ana Volarevic
{"title":"Molecular mechanisms responsible for mesenchymal stem cell-dependent improvement of islet cell transplantation.","authors":"Vladislav Volarevic, Carl Randall Harrell, Crissy Fellabaum, Valentin Djonov, Ana Volarevic","doi":"10.1177/09636897261427908","DOIUrl":"10.1177/09636897261427908","url":null,"abstract":"<p><p>Islet cell transplantation holds great promise for restoring glycemic control in patients with type 1 diabetes. However, its long-term efficacy remains limited due to poor islet survival, immune rejection, and insufficient vascularization. Mesenchymal stem cells (MSCs) have emerged as potent biological adjuvants capable of addressing these challenges through a range of molecular mechanisms. MSCs secrete a variety of growth factors, immunoregulatory and pro-angiogenic molecules that enhance viability of islet cells, modulate the immune response, promote neo-angiogenesis and enhance islet engraftment. In addition, MSC-derived exosomes (MSC-Exos) have been identified as key mediators, delivering regulatory microRNAs and proteins that replicate many of the beneficial effects of MSCs in a cell-free format. MSC-Exos act as small RNA carriers and immunomodulators, promoting islet survival and functional integration. Understanding the molecular interplay between MSCs, their exosomes, and the islet microenvironment provides crucial insights for the development of advanced co-transplantation strategies. Accordingly, in this review article, we summarized current knowledge about molecular mechanisms that are responsible for MSC-dependent improvement of islet cell transplantation and we highlighted the translational potential of MSC and MSC-Exos-based approaches in improving islet graft outcomes for type 1 diabetes.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261427908"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12979893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell TransplantationPub Date : 2026-01-01Epub Date: 2026-02-20DOI: 10.1177/09636897261418580
Elena Bigliardi, Paul Bigliardi, Julianna Goenaga, Nikhil Iyer, Dilmareth Natera-Rodriguez, Madison B Waldron, Walter C Low, Mei Bigliardi-Qi
{"title":"The use of therapeutic exosomes for <i>in vivo</i> wound healing.","authors":"Elena Bigliardi, Paul Bigliardi, Julianna Goenaga, Nikhil Iyer, Dilmareth Natera-Rodriguez, Madison B Waldron, Walter C Low, Mei Bigliardi-Qi","doi":"10.1177/09636897261418580","DOIUrl":"10.1177/09636897261418580","url":null,"abstract":"<p><p>Normal wound healing is a complex, yet critical process. Unfortunately, delayed or impaired wound healing presents a significant burden for numerous patients worldwide. Recent research has demonstrated that exosomes, a subtype of extracellular vesicles, may play a pivotal role in mediating cell-cell communication during wound healing. This narrative review aims to explore the use of exosomes in wound healing, with a focus on <i>in vivo</i> application of exosomes in animal wound models. A total of 73 studies are outlined in this narrative review, exploring either excisional, diabetic, burn, ischemic, or pressure wounds. Overall, the most frequent source of exosomes was adipose-derived mesenchymal stem cells, and the most common application method was local or subcutaneous injection. While these studies demonstrated great promise for the use of exosomes for therapeutic use in wound healing, this review also discusses the challenges and obstacles that will need to be overcome, including standardizing methods, further characterizing exosomes and identifying the optimal sources and doses in the development of exosome therapies.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261418580"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12925034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146257510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell TransplantationPub Date : 2026-01-01Epub Date: 2026-09-02DOI: 10.1177/09636897261486242
Chengjia Mi, Xie Cheng, JinYang Tang, Yang Gao, Jing Zhang, Yan Yang, Guixiang Tan, Chunbing Zheng, Haisong Liu
{"title":"Stem cell strategies for cell replacement therapy in endocrine diseases.","authors":"Chengjia Mi, Xie Cheng, JinYang Tang, Yang Gao, Jing Zhang, Yan Yang, Guixiang Tan, Chunbing Zheng, Haisong Liu","doi":"10.1177/09636897261486242","DOIUrl":"10.1177/09636897261486242","url":null,"abstract":"<p><p>Conventional therapies for endocrine hormone deficiencies, including hormone replacement therapy and solid organ transplantation, are hampered by the lack of physiological regulation or donor shortage, respectively. Directed differentiation of human pluripotent stem cells has opened new avenues for cell replacement therapy; however, research on different endocrine glands has long been conducted in isolation, with limited cross-disciplinary exchange of technical expertise. This Review takes the clinically most advanced stem cell-derived pancreatic β cells as a methodological reference and establishes a three-tier translational challenge model-cell identity, <i>in vivo</i> survival, and functional delivery-to systematically compare the regenerative progress and specific hurdles of thyroid, parathyroid, pituitary, and adrenal cells. We highlight transferable strategies emerging from these lineage-specific studies, including temporal developmental signaling modulation, modular lineage assembly, prevascularization engineering, and hierarchical immunocompatibility design. Through this cross-lineage comparative framework, this Review aims to break the isolated research paradigm and provide a methodological foundation for endocrine regenerative medicine to evolve from isolated efforts toward synergistic advancement.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261486242"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell TransplantationPub Date : 2026-01-01Epub Date: 2026-01-31DOI: 10.1177/09636897251414206
Yu Wang, Jiaying Wu, Xiaobing Huang, Yi Xiao
{"title":"Allogeneic hematopoietic stem cell transplantation for the treatment of chronic active Epstein-Barr virus infection.","authors":"Yu Wang, Jiaying Wu, Xiaobing Huang, Yi Xiao","doi":"10.1177/09636897251414206","DOIUrl":"10.1177/09636897251414206","url":null,"abstract":"<p><p>Chronic active Epstein-Barr virus (CAEBV) infection is a rare and highly lethal lymphoproliferative disorder. The pathological basis of this condition involves Epstein-Barr virus (EBV) persisting in hematopoietic stem cells, driving clonal expansion of T cells or natural killer (NK) cells, and subsequently triggering systemic inflammatory responses and multi-organ failure. Current treatment modalities, encompassing antiviral medications, immunosuppressants, and cytotoxic chemotherapy, offer only transient remissions, with the majority of patients ultimately experiencing relapse. Recent single-cell sequencing and chimera studies have confirmed that EBV-infected hematopoietic stem cells constitute the \"seed\" cell population for CAEBV initiation and maintenance. This finding indicates that allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment known to date that can fully eradicate viral reservoirs and restore normal immunity, suggesting that it may represent a curative strategy. Nevertheless, transplantation timing, donor matching, conditioning intensity, and transplant-related complications have been shown to have a significant impact on long-term prognosis. The clinical decision-making process necessitates a high degree of individualization, incorporating molecular risk factors, disease activity, and comorbidities. Advancing research into the latent-lytic cycle regulation mechanisms of EBV, in addition to the clinical translation of small-molecule inhibitors targeting viral proteins and EBV-specific adoptive cell therapies, holds great promise for the future. One such potential avenue for future research is the development of an integrated \"pre-transplant viral load reduction-post-transplant relapse prevention\" strategy. This approach shows great potential in reducing transplant-related mortality and continuously improving survival outcomes for CAEBV patients.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897251414206"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12861366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146092321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell TransplantationPub Date : 2026-01-01Epub Date: 2026-02-13DOI: 10.1177/09636897261418754
Yue Wang, Jiayu Zhu, Zhonghui Li, Fang Yu, Yuanyuan Fu, Han Gao, Meng Wang, Yuan Liu, Luming Zheng, Qingqing He
{"title":"Mechanisms and clinical prospects of mesenchymal stem cells and their derivatives in treating hypothyroidism-induced injuries: A focus on cardiovascular, skeletal muscle, and nervous systems.","authors":"Yue Wang, Jiayu Zhu, Zhonghui Li, Fang Yu, Yuanyuan Fu, Han Gao, Meng Wang, Yuan Liu, Luming Zheng, Qingqing He","doi":"10.1177/09636897261418754","DOIUrl":"10.1177/09636897261418754","url":null,"abstract":"<p><p>Hypothyroidism, a prevalent endocrine disorder characterized by insidious onset and prolonged progression, leads to metabolic slowdown and multiorgan dysfunction, significantly compromising patients' quality of life. While hormone replacement therapy improves most patients' serum thyroid function, it faces limitations, including individual response variations, lifelong medication requirements, and potential risks, with no reversal of existing tissue damage. In recent years, the mesenchymal stem cells (MSCs) and their derivatives have gained prominence in immunomodulation and regenerative medicine because of their abundant sources, low immunogenicity, potent paracrine effects, and multidirectional differentiation capabilities for tissue repair. Their unique advantages in modulating the immune microenvironment, promoting angiogenesis, reducing fibrosis, and stimulating endogenous cell regeneration offer novel strategies to overcome treatment bottlenecks in hypothyroidism and its complications, effectively repairing thyroid and multiorgan damage in animal models. This review synthesizes literature from the PubMed and Web of Science databases, incorporating relevant basic research and clinical trials. This study examined the systemic impacts of hypothyroidism, evaluated the experimental and clinical roles of the MSCs in thyroid tissue reconstruction and organ protection, and analyzed molecular mechanisms, including immune regulation, the antioxidant stress response, anti-apoptosis, and cellular function restoration. Clinical application potential is assessed alongside critical challenges such as standardized preparation, long-term safety, <i>in vivo</i> homing efficiency, and large-scale production.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261418754"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12905099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146178098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell TransplantationPub Date : 2026-01-01Epub Date: 2026-05-25DOI: 10.1177/09636897261449972
Jiaying Wu, Rubing Zheng, Xi Ming, Xiaojian Zhu, Mi Zhou, Yi Xiao
{"title":"Feasibility of post-induction consolidation with BCMA CAR-T cell therapy in newly diagnosed multiple myeloma not proceeding to ASCT: A preliminary case series.","authors":"Jiaying Wu, Rubing Zheng, Xi Ming, Xiaojian Zhu, Mi Zhou, Yi Xiao","doi":"10.1177/09636897261449972","DOIUrl":"10.1177/09636897261449972","url":null,"abstract":"<p><p>B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell therapy has demonstrated promising efficacy in relapsed/refractory multiple myeloma (MM). However, evidence supporting its use in earlier treatment settings remains limited. This study presents a preliminary case series evaluating the feasibility of BCMA CAR-T cell therapy as post-induction consolidation in newly diagnosed multiple myeloma (NDMM) patients who did not proceed to autologous stem cell transplantation (ASCT). Four patients were included in this analysis. After induction therapy, all patients achieved very good partial response or better and did not proceed to ASCT due to ineligibility or personal preference. They subsequently received BCMA CAR-T cell therapy as consolidation treatment. All patients tolerated the BCMA CAR-T cell infusion well. Cytokine release syndrome occurred in all cases, but was limited to grades 1-2, and no immune effector cell-associated neurotoxicity syndrome was observed. Following therapy, patients maintained or further deepened responses and ultimately reached stringent complete response (sCR) and minimal residual disease (MRD) negativity. During a median follow-up period of 17.8 months, all patients remained in sCR status and MRD negativity without the need for additional anti-tumor therapy, and none experienced relapse or disease progression. These preliminary results suggest that BCMA CAR-T cell therapy as post-induction consolidation is feasible and associated with manageable toxicity in NDMM patients not proceeding to ASCT, warranting further evaluation in larger prospective studies.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261449972"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13201919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148013598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell TransplantationPub Date : 2026-01-01Epub Date: 2026-06-29DOI: 10.1177/09636897261464319
Chen-Yuan Hsiao, Jian-Hong Ye, Chang-Ching Yeh, Pei-Jiun Tsai, Po-Hsun Huang, Cheng-Hsiung Huang, Yu-Show Fu
{"title":"Transplantation of human umbilical mesenchymal stromal cells attenuates heart failure progression in a rat model.","authors":"Chen-Yuan Hsiao, Jian-Hong Ye, Chang-Ching Yeh, Pei-Jiun Tsai, Po-Hsun Huang, Cheng-Hsiung Huang, Yu-Show Fu","doi":"10.1177/09636897261464319","DOIUrl":"10.1177/09636897261464319","url":null,"abstract":"<p><p>Myocardial infarction (MI), mainly caused by coronary artery occlusion, remains a leading cause of death worldwide. Although many patients survive after emergency treatment, chronic MI often develops, underscoring the need for effective therapies. This study evaluated the therapeutic potential of human umbilical mesenchymal stromal cells (HUMSCs) in a rat model with chronic MI. MI was induced by permanent ligation of the left anterior descending artery. Seven days post-ligation, 4×10<sup>6</sup> HUMSCs were transplanted into the peri-infarct myocardium, while an additional 2.5×10<sup>7</sup> HUMSCs were introduced into the mediastinal space around the ligation site. Successful model establishment was confirmed by elevated cardiac biomarkers and characteristic electrocardiographic changes. Echocardiography and magnetic resonance imaging demonstrated significant impairments in myocardial strain dynamics, reduced ejection fraction, and diminished fractional shortening, all of which improved following HUMSC transplantation. The transplantation also reduced macrophage infiltration, increased M2 macrophage polarization, suppressed fibroblast activation, attenuated fibrosis, and promoted angiogenesis, ultimately preserving cardiomyocytes and improving cardiac function. The transplanted HUMSCs were detected in rat's myocardium without differentiating into cardiomyocytes or endothelial cells. These findings suggest that adequate HUMSC transplantation offers a promising therapy to attenuate progression of chronic MI or heart failure.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261464319"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13319773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell TransplantationPub Date : 2026-01-01Epub Date: 2026-07-14DOI: 10.1177/09636897261469013
Juan Ren, Tongxin Zhang, Yuqi Wang, Huachao Zhu, Ruimin Liu, Pengcheng He, Xiaoning Wang
{"title":"Efficacy and safety of mitoxantrone hydrochloride liposome/ thiotepa/ busulfan/fludarabine (MTBF) conditioning regimen for salvage allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory acute myeloid leukemia: A single - Arm prospective clinical trial.","authors":"Juan Ren, Tongxin Zhang, Yuqi Wang, Huachao Zhu, Ruimin Liu, Pengcheng He, Xiaoning Wang","doi":"10.1177/09636897261469013","DOIUrl":"10.1177/09636897261469013","url":null,"abstract":"<p><p>To investigate the efficacy and safety of MTBF as conditioning regimen for salvage allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with relapsed or refractory acute myeloid leukemia (R/R AML). We conducted a single-arm prospective clinical trial (NCT06385808). The main outcome was cumulative incidence of relapse (CIR), and the secondary outcomes were progression-free survival (PFS), overall survival (OS), engraftment time, graft-versus-host disease (GVHD), and non-hematological adverse effects. Twenty-four R/R AML patients from the First Affiliated Hospital of Xi'an Jiaotong University were enrolled, and all achieved engraftment. Mucositis was the predominant toxicity and was managed appropriately. The two-year CIR was 10%. The two-year OS and PFS were 78.9 ± 11.1% and 51.2 ± 19.3%, respectively. Two patients experienced relapse, and three patients died of infection. Subgroup analyses demonstrated that maintenance treatment post-transplantation may improve OS. The MTBF regimen for salvage allo-HSCT in R/R AML exhibited notable anti-leukemia activity and tolerable toxicity. (NCT06385808, Efficacy and Safety of MTBF Conditioning Regimen for Salvageable Allo-HSCT in the Treatment of R/R AML).</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261469013"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13369393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148435257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Generation of bioengineered liver grafts densely recellularized using human liver organoids.","authors":"Keita Sonoda, Hiroshi Yagi, Shogo Nagata, Tomonori Tsuchida, Kotaro Nishi, Toshinori Morisaku, Mana Ohtomo, Shungo Adachi, Satoshi Okamoto, Yu Kamishibahara, Yoshiki Kuse, Hideki Taniguchi, Yuko Kitagawa","doi":"10.1177/09636897261474318","DOIUrl":"10.1177/09636897261474318","url":null,"abstract":"<p><p>Bioengineered livers using decellularized extracellular matrix (ECM) scaffolds hold promise for transplantation therapies. However, conventional recellularization methods involving cell injection via blood vessels encounter challenges in recapitulating the complexity of hepatic tissues, including high cellularity, differentiation hierarchy, and cellular heterogeneity. Here, we developed a methodology termed \"combined single-cell and organoid (CSO) injection.\" We injected human liver organoids (HLOs) and dispersed organoid cells via direct puncture and vascular injection into a decellularized porcine ECM scaffold, respectively. This process facilitated the construction of densely populated and self-organized liver-like tissues (CSO Livers) that formed cell-cell/cell-ECM interactions. The tissues displayed hepatic characteristics, including ALBUMIN secretion, robust expression of liver-associated genes, and cellular heterogeneity comprising hepatocytes, cholangiocytes, as well as stellate-like and endothelial cells. Furthermore, we demonstrated that CSO-Livers functioned as grafts in immunodeficient mice and in a microminipig model of liver fibrosis through transplantation via vascular anastomosis. These findings indicate the applicability of the combined single-cell and organoid (CSO) injection method for generating bioengineered liver grafts using HLOs.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261474318"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell TransplantationPub Date : 2026-01-01Epub Date: 2026-03-24DOI: 10.1177/09636897261433327
Suidong Wang, Yiran Li, Wei Wu, Botao Yan, Jiawen Li, Chuanjiang Li, Jun Yan
{"title":"New advances in the use of patient-derived organoids and mouse models for assessing heterogeneity among metastatic colorectal cancers.","authors":"Suidong Wang, Yiran Li, Wei Wu, Botao Yan, Jiawen Li, Chuanjiang Li, Jun Yan","doi":"10.1177/09636897261433327","DOIUrl":"10.1177/09636897261433327","url":null,"abstract":"<p><p>Metastatic colorectal cancers (mCRCs) exhibit substantial heterogeneity at the genetic, transcriptomic, histological, and microenvironmental levels, which contributes to therapeutic resistance and variable clinical outcomes. Patient-derived organoids (PDOs) and patient-derived xenografts (PDXs) have emerged as powerful platforms for modeling this complex disease. PDOs faithfully recapitulate tumor architecture, molecular features, and heterogeneity, enabling high-throughput drug screening and personalized treatment response prediction. In addition, PDX models maintain tumor-stroma interactions <i>in vivo</i> and accurately reflect histological and pharmacological phenotypes, supporting studies on treatment response and resistance mechanisms. Recent advances indicate that these models capture intratumoral, intertumoral, and interpatient variability; reveal patterns and mechanisms of drug sensitivity heterogeneity; and can be used to predict chemotherapy efficacy. However, limitations remain for both model types. Innovations such as humanized PDX mouse models and immune‒organoid coculture systems are being developed to overcome these barriers. This review summarizes the latest progress in PDO and PDX applications in research on mCRC heterogeneity, highlights their role in dissecting tumor heterogeneity, and discusses future directions for integrating these models into precision oncology.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261433327"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13018711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}