Victoria Lövljung, Mathias Waldén, Mikael Sandell, Peter Damberg, Staffan Holmin, Fabian Arnberg Sandor
{"title":"Trans-Vessel Wall Cell Transplantation, Engraftment, and Tumor Access in the VX2 Rabbit Model.","authors":"Victoria Lövljung, Mathias Waldén, Mikael Sandell, Peter Damberg, Staffan Holmin, Fabian Arnberg Sandor","doi":"10.1177/09636897251313678","DOIUrl":"10.1177/09636897251313678","url":null,"abstract":"<p><p>The trans-vessel wall device (TW-device) is a new endovascular tool for precise and safe delivery of various payloads (cells, viral, modified RNA, chemotherapy, growth factors) in oncology and regenerative medicine. The twofold aim of this study was to assess cell engraftment and tumor growth using the TW-device for endovascular transplantation and to evaluate its ability to directly access solid tumors. We used the VX2 model in the rabbit kidney to compare percutaneously implanted fresh VX2 cells with TW-device injections of cryopreserved VX2 cells. We demonstrated the feasibility of endovascular transplantation (<i>n</i> = 7) of tumor cells, achieving a 57.1% engraftment rate despite cryopreservation, comparable with 70% for percutaneous delivery of fresh cells (<i>n</i> = 10). Re-access using the TW-device was 100% successful (<i>n</i> = 11) with super-selective intratumoral contrast administration without complications. In conclusion, endovascular transplantation of VX2 cells using the TW-device resulted in proliferating cell grafts in the rabbit kidney establishing functional proof that cells indeed survive handling, preparation, and device passage. We also show the TW-device is able to access solid tumor parenchyma allowing precise intraparenchymal administration.This proof-of-concept study open up possibilities for repeated direct parenchymal injections via the endovascular route in any hard to reach organ.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251313678"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051813","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":"Robot-Assisted Stereotactic Microinjection Method for Precision Cell Transplantation in Rat and Canine Models.","authors":"Deqiang Han, Sichang Chen, Yuan Wang, Xueyao Wang, Xingzhe Wang, Tianqi Zheng, Zhiguo Chen","doi":"10.1177/09636897251323351","DOIUrl":"10.1177/09636897251323351","url":null,"abstract":"<p><p>Cell transplantation is a promising approach for addressing neurodegenerative conditions. In this study, we developed a robot-assisted stereotactic microinjection system for transplanting cells. We evaluated the factors that affect cellular graft viability and other properties, including the gauge of the syringe needle and the injection rate. We systematically compared the synchronous withdrawal injection (SWI) and fixed-point injection (FPI) procedures in agarose and rat brain models. <i>In vitro</i> assessments revealed superior dye dispersion with SWI compared to FPI, and <i>in vivo</i> analyses confirmed that SWI reduced the tissue injury and improved cell distribution in the striatum. We applied this robot-assisted technique to evaluate the accuracy and safety of cell transplantation in canine models. Overall, this strategy enhances the accuracy and safety of graft delivery, potentially improving outcomes and advancing therapeutic strategies for the clinical treatment of neurodegenerative disorders.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251323351"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656275","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}
Yiran Li, Wei Wu, Jiaxin Yao, Suidong Wang, Xiufeng Wu, Jun Yan
{"title":"Patient-Derived Tumor Organoids: A Platform for Precision Therapy of Colorectal Cancer.","authors":"Yiran Li, Wei Wu, Jiaxin Yao, Suidong Wang, Xiufeng Wu, Jun Yan","doi":"10.1177/09636897251314645","DOIUrl":"10.1177/09636897251314645","url":null,"abstract":"<p><p>Colorectal cancer (CRC) represents a significant cause of cancer-related mortality on a global scale. It is a highly heterogeneous cancer, and the response of patients to homogeneous drug therapy varies considerably. Patient-derived tumor organoids (PDTOs) represent an optimal preclinical model for cancer research. A substantial body of evidence from numerous studies has demonstrated that PDTOs can accurately predict a patient's response to different drug treatments. This article outlines the utilization of PDTOs in the management of CRC across a range of therapeutic contexts, including postoperative adjuvant chemotherapy, palliative chemotherapy, neoadjuvant chemoradiotherapy, targeted therapy, third-line and follow-up treatment, and the treatment of elderly patients. This article delineates the manner in which PDTOs can inform therapeutic decisions at all stages of CRC, thereby assisting clinicians in selecting treatment options and reducing the risk of toxicity and resistance associated with clinical drugs. Moreover, it identifies shortcomings of existing PDTOs, including the absence of consistent criteria for assessing drug sensitivity tests, the lack of vascular and tumor microenvironment models, and the high cost of the technology. In conclusion, despite their inherent limitations, PDTOs offer several advantages, including rapid culture, a high success rate, high consistency, and high throughput, which can be employed as a personalized treatment option for CRC. The use of PDTOs in CRC allows for the prediction of responses to different treatment modalities at various stages of disease progression. This has the potential to reduce adverse drug reactions and the emergence of resistance associated with clinical drugs, facilitate evidence-based clinical decision-making, and guide CRC patients in the selection of personalized medications, thereby advancing the individualized treatment of CRC.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251314645"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425167","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}
Grisell C Gonzalez, Chris M Li, Ilaria Pasolini, Sophia I Pete, Connor Verheyen, Sofia M Vignolo, Teresa De Toni, Aaron A Stock, Alice A Tomei
{"title":"High-Yield Generation of Glucose-Responsive Pseudoislets From Murine Insulinoma Cells for <i>In Vitro</i> Studies and Longitudinal Monitoring of Graft Survival <i>In Vivo</i>.","authors":"Grisell C Gonzalez, Chris M Li, Ilaria Pasolini, Sophia I Pete, Connor Verheyen, Sofia M Vignolo, Teresa De Toni, Aaron A Stock, Alice A Tomei","doi":"10.1177/09636897251315123","DOIUrl":"10.1177/09636897251315123","url":null,"abstract":"<p><p>Compared to primary pancreatic islets, insulinoma cell-derived 3D pseudoislets offer a more accessible, consistent, renewable, and widely applicable model system for optimization and mechanistic studies in type 1 diabetes (T1D). Here, we report a simple and efficient method for generating 3D pseudoislets from MIN6 and NIT-1 murine insulinoma cells. These pseudoislets are homogeneous in size and morphology (~150 µm), exhibit functional glucose-stimulated insulin secretion (GSIS) up to 18 days (NIT-1) enabling long-term studies, are produced in high yield [>35,000 Islet Equivalence from 30 ml culture], and are suitable for both <i>in vitro</i> and <i>in vivo</i> studies, including for encapsulation studies. To enable non-invasive longitudinal monitoring of graft survival <i>in vivo</i>, we transduced NIT-1 cells with green fluorescent protein-luciferase and confirmed comparable morphology, viability, and GSIS to untransduced cells <i>in vitro</i>. After subcutaneous implantation, we show capability to monitor graft survival in immunodeficient mice, recurrence of autoimmunity in non-obese diabetic mice, and allorejection in C57BL/6 mice. Overall, this platform provides an accessible protocol for generating high yields of 3D pseudoislets and non-invasive longitudinal monitoring of graft survival in different models offer advantages over primary islets for optimization and mechanistic studies of β cell biology, drug discovery, T1D pathogenesis and prevention, and β cell transplantation.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251315123"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063969","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 : 2025-01-01Epub Date: 2025-06-02DOI: 10.1177/09636897251342986
Norio Emoto, Takayuki Anazawa, Kei Yamane, Nanae Fujimoto, Takaaki Murakami, Hiroyuki Fujimoto, Cui Jialin, Satoshi Ishida, Kouki Kurahashi, Aya Izuwa, Hang Su, Kenta Inoguchi, Seiichiro Tada, Kazuyuki Nagai, Etsuro Hatano
{"title":"A novel subcutaneous islet transplantation method using a bioabsorbable medical device to facilitate the creation of a highly vascularized transplantation site.","authors":"Norio Emoto, Takayuki Anazawa, Kei Yamane, Nanae Fujimoto, Takaaki Murakami, Hiroyuki Fujimoto, Cui Jialin, Satoshi Ishida, Kouki Kurahashi, Aya Izuwa, Hang Su, Kenta Inoguchi, Seiichiro Tada, Kazuyuki Nagai, Etsuro Hatano","doi":"10.1177/09636897251342986","DOIUrl":"10.1177/09636897251342986","url":null,"abstract":"<p><p>Subcutaneous transplantation is garnering attention as a potential transplantation site for pluripotent stem cell-derived islet cells to address the shortage of pancreatic islet transplant donors. However, subcutaneous transplantation of cells presents challenges related to angiogenesis, which is necessary for successful islet bioproduction. This study aimed to investigate a novel method for enhancing vascularization at the transplant site and thereby promote islet engraftment using a clinically available bioabsorbable medical device. A nonabsorbable device (agarose) or a bioabsorbable device (collagen-gelatin sheet [CGS]) loaded with basic fibroblast growth factor (bFGF) was implanted subcutaneously in C57BL/6 mice. There were two other groups of mice, one of which was implanted with CGS alone, which acted as a control, and another group that was implanted with bFGF-loaded agarose rods. Subsequently, 200 islets were transplanted into the subcutaneous pre-vascularized sites. An equivalent number of islets was also transplanted into the portal vein (IPTx) to compare transplantation efficacy. Vascularization of the graft site was evaluated before and after transplantation. bFGF significantly enhanced angiogenesis in the CGS mice. The normalization rate of blood glucose levels following islet transplantation in the bFGF-loaded CGS was group comparable to that in the bFGF-loaded agarose rod and IPTx groups. The presence of islets was confirmed using single-photon emission computed tomography (SPECT/CT), histological examination. Furthermore, it was noted that blood glucose levels rapidly increased after graft removal, showing that graft function was crucial to maintain normoglycemia. Importantly, the bFGF-loaded CGS showed a high rate of engraftment. This novel bioabsorbable medical device method exhibited remarkable efficacy in enhancing subcutaneous islet engraftment, potentially paving the way for a more straightforward and less invasive approach for islet cell transplantation in future clinical applications.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251342986"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198340","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":"Advances in the Development and Application of Human Organoids: Techniques, Applications, and Future Perspectives.","authors":"Zhangcheng Zhu, Yiwen Cheng, Xia Liu, Wenwen Ding, Jiaming Liu, Zongxin Ling, Lingbin Wu","doi":"10.1177/09636897241303271","DOIUrl":"10.1177/09636897241303271","url":null,"abstract":"<p><p>Organoids are three-dimensional (3D) cell cultures derived from human pluripotent stem cells or adult stem cells that recapitulate the cellular heterogeneity, structure, and function of human organs. These microstructures are invaluable for biomedical research due to their ability to closely mimic the complexity of native tissues while retaining human genetic material. This fidelity to native organ systems positions organoids as a powerful tool for advancing our understanding of human biology and for enhancing preclinical drug testing. Recent advancements have led to the successful development of a variety of organoid types, reflecting a broad range of human organs and tissues. This progress has expanded their application across several domains, including regenerative medicine, where organoids offer potential for tissue replacement and repair; disease modeling, which allows for the study of disease mechanisms and progression in a controlled environment; drug discovery and evaluation, where organoids provide a more accurate platform for testing drug efficacy and safety; and microecological research, where they contribute to understanding the interactions between microbes and host tissues. This review provides a comprehensive overview of the historical development of organoid technology, highlights the key achievements and ongoing challenges in the field, and discusses the current and emerging applications of organoids in both laboratory research and clinical practice.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897241303271"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058322","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":"Can Islet Transplantation Possibly Reduce Mortality in Type 1 Diabetes.","authors":"Jeffrey S Isenberg, Fouad Kandeel","doi":"10.1177/09636897241312801","DOIUrl":"10.1177/09636897241312801","url":null,"abstract":"<p><p>Islet transplantation (IT) is a successful natural cell therapy. But the benefits are known mostly to individuals with severe type 1 diabetes who undergo IT and the health care professionals that work to make the therapy available, reproducible, and safe. Data linking IT to overall survival in T1D might alter this situation and frame the therapy in a more positive light. Recent analysis of mortality in several cohorts suggests that IT has possible survival benefits when used alone or in conjunction with renal transplantation. Multi-center prospective studies with long-term follow-up of individuals that receive stand-alone IT versus individuals who qualify for but do not undergo the procedure would seem reasonable to undertake to confirm an IT survival benefit.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897241312801"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001072","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 method of pancreatic islet transplantation at the liver surface using a gelatin hydrogel nonwoven fabric.","authors":"Yukiko Endo Kumata, Akiko Inagaki, Yasuhiro Nakamura, Takehiro Imura, Ryusuke Saito, Takumi Katano, Shoki Suzuki, Kazuaki Tokodai, Takashi Kamei, Michiaki Unno, Kimiko Watanabe, Yasuhiko Tabata, Masafumi Goto","doi":"10.1177/09636897251328419","DOIUrl":"https://doi.org/10.1177/09636897251328419","url":null,"abstract":"<p><p>Considering the limitations of intraportal transplantation (Tx), we sought to establish an alternative approach for it-transplanting islets onto the liver surface (LS) by optimizing adipose tissue-derived stem cell (ADSC) co-Tx procedures with a gelatin hydrogel nonwoven fabric (GHNF). In the <i>in vivo</i> study, we examined the use of the GHNF, the effectiveness of islet covering materials, and preferred procedures for ADSC co-Tx using a syngeneic rat model. Immunohistochemical staining was performed to evaluate the extracellular matrix (ECM) expression and angiogenesis. In the <i>in vitro</i> study, we analyzed the culture supernatants to identify crucial factors secreted from ADSCs in different ADSC co-Tx procedures. It was shown that the GHNF should be used to cover the islets but not to embed internally (encapsulate) them. Utilization of the GHNF in LS Tx resulted in significantly better glucose changes (<i>P</i> = 0.0002) and cure rate of diabetic recipients (<i>P</i> = 0.0003) than the use of a common adhesion barrier. Although neovascularization was comparable among groups, ECM reconstitution tended to be higher when the GHNF was used. ADSC co-Tx further enhanced ECM reconstitution only when ADSCs were cultured in the GHNF before islet Tx. Leptin, vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and several chemokines were identified as candidate factors for enhancing ECM reconstitution (<i>P</i> < 0.001). The inhibition assay using antagonist suggested that leptin might be at least in part responsible for the difference in transplant efficiency in distinct ADSC co-Tx methods. This study showed that the GHNF effectively improved the outcomes of LS islet Tx, mainly due to ECM reconstitution around the islets. Furthermore, we established a novel method of LS islet Tx by combining a GHNF with ADSCs, which is equally effective as intraportal Tx.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251328419"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966973","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":"LncRNA <i>XLOC-040580</i> targeted by <i>TPRA1</i> coordinate zygotic genome activation during porcine embryonic development.","authors":"Mengxin Liu, Enhong Li, Haiyuan Mu, Zimo Zhao, Xinze Chen, Jie Gao, Dengfeng Gao, Zhiyu Liu, Jianyong Han, Liang Zhong, Suying Cao","doi":"10.1177/09636897251332527","DOIUrl":"https://doi.org/10.1177/09636897251332527","url":null,"abstract":"<p><p>Long noncoding RNAs (lncRNAs) are crucial in porcine preimplantation embryonic development, yet their regulatory role during zygote genome activation (ZGA) is poorly understood. We analyzed transcriptome data from porcine fetal fibroblasts (PEF), induced pluripotent stem cells (iPS), and preimplantation embryos, identifying ZGA-specific lncRNAs like <i>XLOC-040580</i>, and further predicted its potentially interacting genes <i>TPRA1</i> and <i>BCL2L1</i> via co-expression network. <i>XLOC-040580</i> was knocked down by siRNA microinjection and the expression of ZGA-related genes was detected by qRT-PCR. After microinjecting siRNA targeting <i>TPRA1</i> and <i>BCL2L1</i> at the one-cell stage, we counted the blastocyst development rate. The blastocyst development rate was consistent with the results from si-XLOC-040580 after si-<i>TPRA1</i>. Through dual-luciferase reporter assays, we found that <i>XLOC-040580</i> was a downstream target of <i>TPRA1</i>. To further elucidate the mechanism of <i>XLOC-040580</i>, Single-cell mRNA sequencing after <i>XLOC-040580</i> knockdown revealed its regulatory network involved in embryonic developmental defects. Transcriptome analysis revealed that <i>XLOC-040580</i> was specifically expressed during zygote activation. Knockdown of <i>XLOC-040580</i> decreased the blastocyst development rate and reduced both the total blastocyst cell number and TE cell number. <i>TPRA1</i> and <i>BCL2L1 were</i> specifically co-expressed with <i>XLOC-040580</i> during ZGA stage, and <i>TPRA1</i> could interact with the promoter region of <i>XLOC-040580</i> and regulate its expression. Knockdown of <i>TPRA1</i> or <i>XLOC-040580</i> blocked porcine embryonic development by affecting the expression of ZGA-related genes. We found and validated that lncRNA <i>XLOC-040580</i> played a key role in the ZGA process, which was regulated by <i>TPRA1</i>. These results implied that the functional axis of <i>TPRA1</i>-<i>XLOC-040580</i>-downstream genes involved in ZGA-related functions also coordinated early embryonic development in porcine.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251332527"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967168","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":"Effects of Combined Intrathecal Mesenchymal Stem Cells and Schwann Cells Transplantation on Neuropathic Pain in Complete Spinal Cord Injury: A Phase II Randomized Active-Controlled Trial.","authors":"Mohammadhosein Akhlaghpasand, Roozbeh Tavanaei, Maede Hosseinpoor, Reza Heidari, Ida Mohammadi, Mohsen Chamanara, Melika Hosseinpour, Alireza Zali, Reza Mosaed, Saeed Oraee-Yazdani","doi":"10.1177/09636897241298128","DOIUrl":"10.1177/09636897241298128","url":null,"abstract":"<p><p>Neuropathic pain is a debilitating complication following spinal cord injury (SCI). Currently, effective treatments for SCI-induced neuropathic pain are highly lacking. This clinical trial aimed to investigate the efficacy of combined intrathecal injection of Schwann cells (SCs) and bone marrow-derived mesenchymal stem cells (BMSCs) in improving SCI-induced neuropathic pain. This study was a parallel-group, randomized, open-label, active-controlled phase II trial with two arms, including treatment and control groups. Patients with complete SCI-induced neuropathic pain in the treatment group received a single combined intrathecal injection of BMSCs and SCs. Study outcome measures were International SCI Pain Basic Data Set (ISCIPBDS) and World Health Organization (WHO) Quality of Life Assessment Instrument (WHOQOL-BREF). A total of 37 (55.2%) and 30 (44.8%) patients in the treatment and control groups were followed up for 6 months, respectively. Significant reductions in mean scores of interference items in the treatment group, including daily activities (<i>P</i> < 0.001), mood (<i>P</i> < 0.001), and sleep (<i>P</i> < 0.001), were found at 6 months after the injection compared with the control one. Similarly, pain frequency (<i>P</i> = 0.002), mean (<i>P</i> = 0.001), and worst (<i>P</i> = 0.001) numeric rating scale (NRS) pain intensity scores showed significant reductions in the treatment group after 6 months compared with the control one. Based on multiple regression analysis controlled for potential confounders, significant associations between changes in all outcome measures over the study period and the treatment group were found. This clinical trial indicated the efficacy of combined cell therapy in improving the neuropathic pain and quality of life in complete SCI patients. Future investigations should evaluate the effects of combination of this strategy with other existing therapies for SCI-induced neuropathic pain. This clinical trial was also registered prospectively at the Iranian Registry of Clinical Trials (IRCT20200502047277N8).</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897241298128"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057943","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}