Cell Transplantation最新文献

{"title":"Stem cell-based approaches for alopecia: A narrative review of current and emerging treatment strategies.","authors":"Pitsunan Paphawannasri, Tulyapruek Tawonsawatruk, Jitrada Phetfong, Aungkura Supokawej","doi":"10.1177/09636897261454219","DOIUrl":"10.1177/09636897261454219","url":null,"abstract":"<p><p>The natural cycle of hair growth and shedding is continuous. However, an abnormal rate of hair regrowth can signal alopecia, a condition characterized by excessive hair loss and thinning. Alopecia is a common dermatological concern globally, affecting individuals across all ages and sexes, often resulting in psychological distress and diminished quality of life. Despite the availability of various current therapy options such as minoxidil, finasteride, JAK inhibitors, low-level laser, and hair transplantation, these approaches are often limited by variable efficacy or side effects. Consequently, there is growing research interest in regenerative therapies using stem cells as a promising avenue to overcome these shortcomings. Stem cells, characterized by their ability to self-renew and differentiate into multiple cell types, offer the potential to promote hair follicle regeneration. Among the different stem cell types under investigation, hair follicle stem cells (HFSCs), mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs) have attracted attention due to their regenerative capabilities and immunomodulatory properties. This narrative review explores the underlying causes of alopecia, current and emerging therapies, particularly emphasizing the therapeutic potential of stem cells and their specialized roles in promoting a supportive environment for the hair follicle and scalp. It also examines ongoing clinical and preclinical studies involving stem cell-based therapies for hair loss, aiming to assess their feasibility as future clinical solutions for alopecia.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261454219"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13241688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148161898","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":"Stem cell and extracellular vesicle therapies for wound healing: An umbrella review of predominantly diabetic and preclinical evidence.","authors":"Nadiar M Mussin, Amin Tamadon, Mahdi Mahdipour, Kulyash R Zhilisbayeva, Madina A Kurmanalina, Akmaral Baspakova, Mustafa R Rysuly, Amirkan A Azimbayev, Vyacheslav B Ogay, Ramazon Safarzoda Sharoffidin","doi":"10.1177/09636897261452345","DOIUrl":"10.1177/09636897261452345","url":null,"abstract":"<p><p>Chronic and complex skin wounds, including diabetic ulcers and burns, represent a major clinical challenge with substantial morbidity and healthcare costs. Regenerative approaches have evolved from stem cell-based therapies toward stem cell-free strategies, particularly mesenchymal stroma/stem cell-derived extracellular vesicles (MSC-EVs). However, the relative strength, consistency, and translational readiness of these approaches remain unclear. The aim of this study is to synthesize and critically appraise evidence from systematic reviews and meta-analyses on cell-based and cell-free regenerative therapies for wound healing, with emphasis on clinical relevance, methodological quality, and recent developments. An umbrella review was conducted in accordance with PRISMA 2020 guidance. PubMed/MEDLINE, Scopus, and Web of Science were searched for systematic reviews and meta-analyses published in English within the last 5 years. Eligible reviews evaluated cell-based therapies and/or extracellular vesicle-based interventions for skin wound healing in clinical and/or animal models. Methodological quality was assessed using AMSTAR-2, and overlap of primary studies was evaluated using the corrected covered area (CCA). Seven systematic reviews and meta-analyses were included, encompassing both clinical and preclinical evidence. Notably, the majority of included evidence was derived from diabetic wound models, particularly in preclinical animal studies. Cell-based therapies demonstrated clinically relevant benefits in specific settings, such as autologous skin cell suspensions for burns and biologic skin substitutes for diabetic foot ulcers, although certainty of evidence was low to moderate. In contrast, MSC-EVs showed large and consistent effects on wound closure, angiogenesis, collagen deposition, and inflammatory modulation in preclinical models. No randomized human trials of EV-based wound therapies were identified. Current evidence suggests a paradigm shift toward stem cell-free regenerative strategies in wound healing. While cell therapies have limited but established clinical roles, MSC-EVs offer strong preclinical efficacy and translational potential. Standardization, regulatory alignment, and well-designed clinical trials are required to enable safe clinical implementation.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261452345"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13420067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599335","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":"An Immunological and Translational Framework for Interspecies Exogenic Liver Transplantation.","authors":"Joseph Sushil Rao, Anala Shetty, Sabarinathan Ramachandran, Walter C Low, Clifford J Steer","doi":"10.1177/09636897261479189","DOIUrl":"10.1177/09636897261479189","url":null,"abstract":"<p><p>Liver transplantation remains the only definitive therapy for end stage liver disease, yet its application is fundamentally constrained by donor organ scarcity. Despite advances in organ preservation, marginal graft utilization, and xenotransplantation, a scalable source of functional liver tissue has not been realized. Blastocyst complementation has emerged as a novel strategy to generate exogenic organs, enabling the development of human derived hepatocytes within a xenogeneic host. The approach introduces a distinct biological paradigm where human parenchymal cells coexist with partial xenogeneic non-parenchymal compartments, resulting in compartmentalized immunogenicity. Efficient human-porcine blastocyst complementation remains an evolving technology, and functional exogenic humanized livers have yet to be demonstrated in large-animal transplant models. We examine exogenic liver transplantation through an immunology-first, clinical framework with emphasis on early graft injury driven predominantly by innate immune mechanisms at the vascular interface, including complement activation, macrophage mediated clearance, thrombocytopenia, and coagulation dysregulation as a major barrier observed in liver xenotransplantation. While adaptive immune responses may be attenuated due to reduced antigenic burden, residual xenogeneic endothelial and stromal compartments remain critical drivers of immune activation. We highlight exogenic hepatocyte transplantation as a potential translational bridge, enabling functional validation of chimerism-derived human hepatocytes <i>in vivo</i> while bypassing the vascular incompatibility inherent to whole organ transplantation. This cell-based therapy could offer a platform before the clinical realization of whole exogenic liver transplantation. We propose a phased immunomodulatory approach centered on early control of innate and humoral injury using induction therapy, plasmapheresis, and complement modulation, followed by tolerance-oriented tapering of maintenance immunosuppression. Finally, we outline a translational pathway incorporating preclinical validation, <i>ex vivo</i> perfusion, and human decedent transplant models, while addressing ethical, biosafety, and logistical considerations. Exogenic liver transplantation has the potential to represent a transformative strategy to generate scalable, immunologically optimized grafts and redefine the future of liver transplantation.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261479189"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788644","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":"Bioactive molecule delivery platforms in regenerative endodontic therapy: A systematic review and meta-analysis.","authors":"Kanwalpreet Kaur, Rayan Ibrahim H Binduhayyim, Ravinder S Saini, Shashit Shetty Bavabeedu, Sunil Kumar Vaddamanu, Anna Avetisyan, Artak Heboyan","doi":"10.1177/09636897251407385","DOIUrl":"10.1177/09636897251407385","url":null,"abstract":"<p><p>This systematic review examines emerging delivery systems for bioactive molecules within regenerative endodontic therapy (RET) where hydrogels, nanogels, and polymeric nanoparticles along with advanced nanocarriers such as liposomes aquasomes, vesosomes, and mesoporous silica nanoparticles form the primary focus. The extensive literature search in PubMed, Scopus, and Web of Science databases (until August 2025) yielded a total of 47 eligible articles, including <i>in vitro</i>, <i>ex vivo</i>, animal, and a few clinical studies. Hydrogels emerged as a significant category, showcasing enhanced regenerative effects when used for the sustained release of various growth factors such as transforming growth factor-beta (TGF-β₁), bone morphogenetic protein-2 (BMP-2), and vascular endothelial growth factor (VEGF). This was associated with improved angiogenesis and odontogenic differentiation. Nanogels exhibited high protein-loading efficiency and facilitated the differentiation of dental pulp stem cells, while polymeric nanoparticles demonstrated prolonged antibiotic and growth factor delivery with lower cytotoxicity. Among advanced nanocarriers, mesoporous silica nanoparticles showed promising potential for controlled release of growth factors and the formation of pulp-like tissues in animal models. In summary, the selected platforms for the delivery of bioactive molecules within RET show significant promise in terms of enhancing cell viability, bioactivity, and tissue regeneration. The findings indicate a practical pathway for clinicians aiming to achieve successful pulp-dentin tissue regeneration through translation research.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897251407385"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12775354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909960","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":"CAR-T cell therapy: A new dawn in the treatment of autoimmune disease.","authors":"Sijia Yan, Xiaojian Zhu, Yi Xiao","doi":"10.1177/09636897251414211","DOIUrl":"10.1177/09636897251414211","url":null,"abstract":"<p><p>Autoimmune diseases (AIDs) are a class of diseases caused by autoimmune intolerance, which can be divided into systemic and organ-specific diseases. AIDs affect approximately 10% of the global population and rank among the leading causes of disability and mortality. At present, immunosuppressive agents are the first choice for the treatment of AIDs. B-cell-targeted therapies-particularly CD20 monoclonal antibodies-have brought new hope for systemic AIDs, yet a subset of patients still respond poorly. As a rapidly developing cellular immunotherapy technology, Chimeric antigen receptor T cell (CAR-T) plays an important role in the treatment of hematological malignancies. CAR-T targeting B-cell-specific antigens can rapidly deplete circulating B cells, thereby reducing the formation of autoantibodies, which has become the basis for research on CAR-T in the treatment of autoimmune diseases. Currently, many studies are underway, and CAR-T and its derivative therapies bring new hope for the treatment of autoimmune diseases.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897251414211"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12819979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008991","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":"A novel GMP-manufactured medicinal product candidate composed of NK and γδ T cells as adjunct immunotherapy for hematopoietic stem cell transplantation.","authors":"Fabio Morandi, Martina Della Lastra, Gino Tripodi, Federica Sabatini, Claudia Cocco, Marco Risso, Roberto Gramignoli, Federico Zara, Irma Airoldi","doi":"10.1177/09636897251374248","DOIUrl":"10.1177/09636897251374248","url":null,"abstract":"<p><p>γδ T lymphocytes and NK cells are effective to kill tumors or viral-infected cells avoiding graft versus host disease (GvHD), thus they have attracted high interest as potential tool for adoptive cell therapy. We generated an advanced therapy medicinal product (ATMP) composed of mature γδ T and NK cells to provide an innovative tool to protect patients against tumor relapse and life-threatening infection after haploidentical hematopoietic stem cell transplantation. The ATMP was manufactured and validated in a GMP facility and was obtained from leukapheresis stimulated with zoledronic acid and IL-2, afterward depleted of αβ T lymphocytes using the CliniMACS Prodigy. The ATMP is characterized by high homogeneity, cell viability, cytotoxic abilities, stability after cryogenic preservation, and it was virtually free of αβ T and B lymphocytes. Both NK and γδ T cells were activated and characterized by high expression of cytotoxic and activating receptors including NKG2D, CD16, NKp30, NKp44, and NKp46. Furthermore, γδ T lymphocytes and NK cells were cytotoxic against myeloid leukemia or neuroblastoma cells. In conclusion, we implemented a novel ATMP to be shortly translated into clinical practice, which may be used in the post-transplant phase as efficacious immunotherapy in neuroblastoma and leukemic pediatric patients.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897251374248"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12953997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316605","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":"The landscape of mitochondrial transplantation: A bibliometric analysis.","authors":"Xiaojuan Yang, Miaohui Wang, Xuhang Fan, Minheng Zhang, Siyao Chen, Yue Liu, Haixia Fan","doi":"10.1177/09636897261427903","DOIUrl":"10.1177/09636897261427903","url":null,"abstract":"<p><p>Recent years have witnessed rapid progress in mitochondrial transplantation (MT) as a novel strategy for restoring mitochondrial function in diverse pathological conditions, including somatic mitochondrial transfer and reproductive mitochondrial replacement therapy. With its expanding applications in regenerative medicine and disease modeling, systematic quantitative evaluation of the global MT research landscape remains limited. To address this gap, we performed a bibliometric analysis of publications indexed in the Web of Science Core Collection from 1996 to 2024, with cross-database validation using Scopus. CiteSpace, VOSviewer, and the R package <i>bibliometrix</i> were applied to assess publication trends, collaboration networks, co-citation patterns, and keyword co-occurrence. In total, 1104 articles and reviews were included. The results revealed rapid growth in MT-related research, with the United States and China as leading contributors. <i>Mitochondrion</i> emerged as the most influential journal, while Yamada Y, Harashima H, and McCully JD were recognized as key authors. High-frequency keywords highlighted major themes including mitochondrial transfer, mesenchymal stem cells, and ischemia-reperfusion injury. Emerging terms such as extracellular vesicles, tunneling nanotubes, and advanced delivery systems, particularly the MITO-Porter platform, reflected current research frontiers. Overall, this study provides a comprehensive overview of global research trends and evolving directions in mitochondrial transplantation.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261427903"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12966552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364174","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":"Cryopreservation of hepatocytes: Impact of long-term storage and organ donor factors on cell quality for clinical applications.","authors":"Kadriye Güven, Valeria Iansante, Sharon C Lehec, Ragai R Mitry, Anil Dhawan, Céline Filippi","doi":"10.1177/09636897261417050","DOIUrl":"10.1177/09636897261417050","url":null,"abstract":"<p><p>Liver transplantation is the only curative option for end-stage liver disease, but its applicability is limited by donor shortages. Hepatocyte transplantation offers a promising alternative, particularly for pediatric acute liver failure, yet its success relies on the availability of viable cells. Cryopreservation enables off-the-shelf use, though long-term storage may impair cell quality. This study investigates whether cryostorage duration, donor characteristics, and organ retrieval parameters affect the viability and functionality of cryopreserved primary human hepatocytes (PHHs). We conducted a retrospective analysis of 144 thawing events across 81 GMP-grade hepatocyte batches, cryopreserved for up to 14 years. Donor age ranged from 3 days to 70 years. Viability and functionality were assessed using MTT assays, albumin and urea secretion, and CYP450 activity. Linear regression was used to analyze correlations (<i>P</i> < 0.05 considered significant). The cryopreservation duration had no significant impact on hepatocyte viability or function, confirming that clinical-grade PHHs can maintain quality for up to 14 years. However, donor age correlated negatively with post-thaw viability (<i>R</i>² = 0.035, <i>P</i> = 0.029), yield (<i>R</i>² = 0.039, <i>P</i> = 0.041), and metabolic activity (<i>R</i>² = 0.278, <i>P</i> = 0.008), while showing a positive correlation with induced ethoxy resorufin O-demethylation (EROD) function (<i>R</i>² = 0.432, <i>P</i> = 0.020). Donor body mass index (BMI) showed significant negative associations with viability (<i>R</i>² = 0.075, <i>P</i> = 0.003), yield (<i>R</i>² = 0.069, <i>P</i> = 0.011), and metabolic activity (<i>R</i>² = 0.267, <i>P</i> = 0.019). Cold ischemia time (CIT) showed a weak negative correlation with viability (<i>R</i>² = 0.151, <i>P</i> < 0.0001), particularly when CIT exceeded ~10 h and viability fell below 60%. Clinical-grade cryopreserved hepatocytes retain viability and function for over a decade. CIT, donor BMI, and age impacted post-thaw quality, while warm ischemia time (WIT), within our current criteria, and storage duration had minimal impact. These findings support refining donor selection to improve cryopreservation outcomes.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261417050"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13103496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721828","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":"Immunophenotypic characterization and clinical relevance of passage number in umbilical cord mesenchymal stromal cells: A review.","authors":"Lim Fang, Gayaatri Ravindran, Maimonah Eissa Al-Masawa, Nuradilla Mohamad-Fauzi, Marjan Sadat Seghayat, Agani Salsabila, Pezhman Hafez","doi":"10.1177/09636897261433504","DOIUrl":"10.1177/09636897261433504","url":null,"abstract":"<p><p>Umbilical cord mesenchymal stromal cells (UC-MSCs) are emerging as leading stem cells in regenerative medicine due to their high proliferative capacity, potent immunomodulatory effects, and non-invasive collection. However, the absence of standardized guidance on optimal passage number and tissue-specific characterization criteria limits clinical translation, raising concerns about variability in potency, genomic stability, and safety. This review synthesizes evidence on how <i>in vitro</i> passaging alters UC-MSC properties, including purity, proliferation, senescence, genomic integrity, differentiation, and immunomodulation. Preclinical data suggest that UC-MSCs tolerate extended passaging better than MSCs derived from other sources, with several functional attributes preserved up to later passages. Clinical evidence indicates that early to middle passages (P3-P5) achieve the best balance between scalability and therapeutic efficacy. We further propose an updated immunophenotypic framework incorporating tissue-specific positive and negative markers to enhance clinical-grade characterization. Establishing harmonized passage guidelines and potency assays is essential to maximize reproducibility, safety, and the translational potential of UC-MSC therapies.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261433504"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13039615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580712","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":"Intramedullary mesenchymal stromal cell transplantation in humans: Procedural safety and oncological risk reassessment.","authors":"Caroline Nonnarath, Nicolas Serratrice","doi":"10.1177/09636897261466805","DOIUrl":"10.1177/09636897261466805","url":null,"abstract":"<p><p>Intramedullary cellular transplantation within the human spinal cord has historically been regarded as a highly experimental intervention associated with substantial theoretical risk. However, cumulative clinical evidence progressively challenges this perception. Multiple early-phase clinical studies have demonstrated the technical feasibility and procedural tolerability of intramedullary and intralesional cellular delivery in spinal cord injury (SCI), employing heterogeneous cellular products, including bone marrow-derived mononuclear cells, mesenchymal stromal cells (MSCs), and neural stem cells. Despite considerable heterogeneity in cellular composition, dosing strategies, injection volumes, and delivery paradigms, severe injection-related complications remain uncommon. Reported adverse events are predominantly mild and transient, while procedure-induced neurological deterioration has not emerged as a reproducible safety signal. These observations suggest that controlled spinal cellular administration may represent a biologically tolerated intervention rather than an intrinsically destabilizing procedure. Beyond procedural considerations, long-term biological safety remains a central dimension of translational evaluation. While theoretical concerns persist - particularly regarding tumorigenesis, clonal selection, and potential genomic instability associated with <i>ex vivo</i> MSC expansion - currently available clinical data have not identified reproducible or causally attributable neoplastic transformation signals within currently reported follow-up durations. Interpretation of long-term safety outcomes therefore requires careful distinction between theoretical biological plausibility and empirical clinical observations. In parallel, minimally manipulated autologous cellular products such as freshly isolated stromal vascular fraction (SVF) introduce a complementary translational framework. By preserving physiological cellular heterogeneity and eliminating risks associated with <i>ex vivo</i> expansion, SVF-based approaches further emphasize the need to reinterpret cellular variability as an intrinsic biological property rather than a marker of product instability. Collectively, available evidence supports consideration of multidimensional safety frameworks integrating procedural, short-term biological, and long-term theoretical domains. Future progress will depend on harmonized reporting standards, extended longitudinal evaluation, and large-scale collaborative datasets capable of refining biologically grounded safety models for spinal cellular therapies.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"35 ","pages":"9636897261466805"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13346740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403654","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}