Cell Transplantation最新文献

{"title":"Impact of Tacrolimus, Sirolimus, Age, and Body Mass Index on the Occurrence of Skin Cancer and Islet Dysfunction After Transplantation.","authors":"Christopher Orr, Jeannette Stratton, Mohamed El-Shahawy, Elena Forouhar, Alice Peng, Gagandeep Singh, Keiko Omori, Meirigeng Qi, Fouad Kandeel","doi":"10.1177/09636897241309412","DOIUrl":"10.1177/09636897241309412","url":null,"abstract":"<p><p>Herein, we characterized the percentage of tacrolimus to the combined sirolimus and tacrolimus trough levels (tacrolimus %) observed during islet transplant-associated immune suppression therapy with post-transplant skin cancer. Although trough levels of tacrolimus and sirolimus were not different (<i>P</i> = 0.79, 0.73, respectively), high tacrolimus % resulted in a 1.32-fold increase in skin cancer odds when adjusting for age, sex, body mass index (BMI), and use of mycopheonlate mofetil (MMF; <i>p</i> = 0.039). Skin cancer patients were likely to have been older but not differ significantly (mean difference 12 years, <i>P</i> = 0.056), but age was significantly associated with a 1.22-fold increase in adjusted skin cancer odds (<i>P</i> = 0.046). BMI was inversely associated with skin cancer, with an adjusted odds ratio (OR) of 0.40 (<i>P</i> = 0.022). High tacrolimus % (>35) resulted in a 4.6-fold increase in skin cancer frequency, whereas sirolimus above 75% of the combined therapy led to a 5.2-fold increase in islet graft dysfunction (IGD) events/year. By calculating the maximum safe exposure (MSE) to tacrolimus % according to patient age and BMI, we found that cumulative months spent above MSE was predictive of skin cancer (1.20-fold increase, <i>P</i> = 0.003). Individuals exceeding the MSE for 1 year were 9.2 times more likely to develop skin cancer (<i>P</i> = 0.008). Results suggest that strategies targeting immunosuppression ratios based on age and BMI may minimize cancer risk while improving graft survival and function.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897241309412"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11713960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945288","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":"Shorter Digestion Times of Donor Islets Is Associated With Better Islet Graft Function After Islet Transplantation.","authors":"Chia-Hao Wang, Christopher Orr, Jeannette Hacker-Stratton, Mohamed El-Shahawy, Keiko Omori, Meirigeng Qi, Fouad Kandeel","doi":"10.1177/09636897241310989","DOIUrl":"10.1177/09636897241310989","url":null,"abstract":"<p><p>Although islet transplantation is effective in reducing severe hypoglycemia events and controlling blood glucose in patients with type 1 diabetes, maintaining islet graft function long-term is a significant challenge. Islets from multiple donors are often needed to achieve insulin independence, and even then, islet function can decline over time when metabolic demand exceeds islet mass/insulin secretory capacity. We previously developed a method that calculated the islet graft function index (GFI) and a patient's predicted insulin requirement (PIR) using mathematical nonlinear regression. Both PIR and GFI could be used by physicians as tools to monitor islet graft function and to guide supplementing the patient with exogenous insulin to prevent beta-cell exhaustion. This study investigates the factors relating to the islet preparation process, as well as donor and recipient characteristics, and assessed their associations with PIR and GFI after transplantation. The goal is to determine the most relevant factors that influence islet graft function after transplantation. We examined the effects of donor and recipient characteristics, and islet processing factors on posttransplanted PIR and GFI. The PIR and GFI at 3 months were calculated using patients' baseline insulin intake, posttransplant 2-h postprandial blood glucose, and glucagon-stimulated C-peptide. Thirteen transplants that resulted in progressive decline in patients' weekly averaged insulin intake over the initial weeks after transplant (assuming constant glucose level) with available 3-month PIR and GFI data were chosen for the investigation. Univariate analyses were performed to assess the effects of donor and recipient characteristics and islet processing factors on islet graft function as reflected by PIR and GFI. The PIR and GFI were treated as continuous response variables in separate linear regression models. Shorter digestion time of isolated donor islets were associated with lower PIR (<i>P</i> = 0.014) and a higher GFI (<i>P</i> = 0.027) after transplantation. Islet injury related to digestion enzyme exposure influenced islet function as estimated using PIR and GFI post-transplantation.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897241310989"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063973","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":"Role of Leucine-Rich Repeat-Containing G-Protein-Coupled Receptors 4-6 (LGR4-6) in the Ovary and Other Female Reproductive Organs: A Literature Review.","authors":"Yu-Hsun Chang, Kun-Chi Wu, Kai-Hung Wang, Dah-Ching Ding","doi":"10.1177/09636897241303441","DOIUrl":"10.1177/09636897241303441","url":null,"abstract":"<p><p>Leucine-rich repeat-containing G-protein-coupled receptors regulate stem cell activity and tissue homeostasis within female reproductive organs, primarily through their interaction with the Wnt/β-catenin signaling pathway. LGR4-6 are increasingly recognized for their roles in organ development, regeneration, and cancer. This review aims to provide a comprehensive overview of the roles of LGR4-6 in female reproductive organs, highlighting their significance in normal physiology and disease states, specifically in the context of ovarian cancer. LGR4 is essential for the proper development of the female reproductive system; its deficiency leads to significant reproductive abnormalities, including delayed menarche and follicle development issues. LGR5 is a well-established marker of stem cells in the ovary and fallopian tubes. It has been implicated in the pathogenesis of high-grade serous ovarian cancer. LGR6, while less studied, shares functional similarities with LGR5 and can maintain stemness. It contributes to chemoresistance in ovarian cancer. LGR6 is a marker for fallopian tube stem cells and is involved in stem cell maintenance and differentiation. LGR4-6 regulate the pathophysiology of female reproductive tissues. LGR4-6 are promising therapeutic targets for treating reproductive cancers and other related disorders. Molecular mechanisms underlying the functions of LGR4-6 should be studied.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897241303441"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057898","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":"Cryopreserved Umbilical Cord Mesenchymal Stem Cells Show Comparable Effects to Un-Cryopreserved Cells in Treating Osteoarthritis.","authors":"Bo Yan, Huixin Chen, Li Yan, Qiang Yuan, Le Guo","doi":"10.1177/09636897241297631","DOIUrl":"10.1177/09636897241297631","url":null,"abstract":"<p><p>Non-cryo and hypothermic preservations are two available options for short-term storage of living cells. For long-term cell storage, cryopreservation is an essential procedure as it prolongs the storage time, allowing for the transport and testing of cells, as well as the establishment of cell banks. But it is unclear whether cryopreservation reduces the therapeutic effects of human umbilical cord mesenchymal stem cells (hucMSCs) on osteoarthritis (OA). To investigate this, we compared the basic biological characteristics and the anti-OA efficacy of un-cryopreserved hucMSCs (UC-MSCs) and cryopreserved hucMSCs (C-MSCs). A mono-iodoacetate-induced rat OA model was established to evaluate the anti-OA properties of UC-MSCs and C-MSCs. And the conditioned medium of UC-MSCs (UC-CM) and cell freezing medium of C-MSCs (C-CFM) were collected for the mechanism study. No significant differences were found between UC-MSCs and C-MSCs in cell viability, immunophenotype, and trilineage differentiation capacity. In vivo, UC-MSCs and C-MSCs exhibited similar cartilage-repairing effects by attenuating pain and alleviating pathological changes in OA rat joints. In vitro, C-CFM and UC-CM promoted the proliferation of chondrocytes, improved the expression of anabolism-related molecules (<i>Col2</i>, COL2, and SOX9), and decreased the expression of catabolism-related molecules (<i>Adamts5</i>, <i>Mmp13</i>, <i>Il6</i>, COL10, and MMP13). These results indicated that UC-MSCs and C-MSCs had comparable anti-OA effects, and cryopreservation did not alter the anti-OA capability of hucMSCs, which provides further support for clinical use of C-MSCs in treating OA.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897241297631"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057916","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":"Mesenchymal Stem Cell-Derived Extracellular Vesicles for Regenerative Applications and Radiotherapy.","authors":"Ning Wang, Feifei Ma, Huijuan Song, Ningning He, Huanteng Zhang, Jianguo Li, Qiang Liu, Chang Xu","doi":"10.1177/09636897241311019","DOIUrl":"10.1177/09636897241311019","url":null,"abstract":"<p><p>Tissue repair is an extremely crucial part of clinical treatment. During the course of disease treatment, surgery, chemotherapy, and radiotherapy cause tissue damage. On the other hand, Normal tissue from accidental or therapeutic exposure to high-dose radiation can cause severe tissue damage. There is an urgent need for developing medical countermeasures against radiation injury for tissue repair. Tissue repair involves the regeneration, proliferation, differentiation, and migration of tissue cells; imbalance of local tissue homeostasis, progressive chronic inflammation; decreased cell activity and stem cell function; and wound healing. Although many clinical treatments are currently available for tissue repair, they are expensive. The long recovery time and some unavoidable complications such as cell damage and the inflammatory reaction caused by radiotherapy have led to unsatisfactory results. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have similar tissue repair functions as MSCs. In tissue damage, EVs can be used as an alternative to stem cell therapy, thereby avoiding related complications such as immunological rejection. EVs play a major role in regulating tissue damage, anti-inflammation, pro-proliferation, and immune response, thus providing a diversified and efficient solution for the repair of disease- and radiotherapy-induced tissue damage. This article reviews the research progress of mesenchymal stem cell-derived EVs in promoting the repair of tissue including heart, lung, liver, intestine, skin, blood system, central nervous system, and tissue damage caused by radiotherapy, thereby aiming to offer new directions and ideas for the radiotherapy and regenerative applications.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897241311019"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11713979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945309","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":"Perspectives and Limitations of Mesenchymal Stem Cell-Based Therapy for Corneal Injuries and Retinal Diseases.","authors":"Barbora Hermankova, Eliska Javorkova, Katerina Palacka, Vladimir Holan","doi":"10.1177/09636897241312798","DOIUrl":"10.1177/09636897241312798","url":null,"abstract":"<p><p>The eye represents a highly specialized organ, with its main function being to convert light signals into electrical impulses. Any damage or disease of the eye induces a local inflammatory reaction that could be harmful for the specialized ocular cells. Therefore, the eye developed several immunoregulatory mechanisms which protect the ocular structures against deleterious immune reactions. This protection is ensured by the production of a variety of immunosuppressive molecules, which create the immune privilege of the eye. In addition, ocular cells are potent producers of numerous growth and trophic factors which support the survival and regeneration of diseased and damaged cells. If the immune privilege of the eye is interrupted and the regulatory mechanisms are not sufficiently effective, the eye disease can progress and result in worsening of vision or even blindness. In such cases, external immunotherapeutic interventions are needed. One perspective possibility of treatment is represented by mesenchymal stromal/stem cell (MSC) therapy. MSCs, which can be administered intraocularly or locally into diseased site, are potent producers of various immunoregulatory and regenerative molecules. The main advantages of MSC therapy include the safety of the treatment, the possibility to use autologous (patient's own) cells, and observations that the therapeutic properties of MSCs can be intentionally regulated by external factors during their preparation. In this review, we provide a survey of the immunoregulatory and regenerative mechanisms in the eye and describe the therapeutic potential of MSC application for corneal damages and retinal diseases.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897241312798"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037316","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":"Tumor Necrosis Factor Receptor 1 Is Required for Human Umbilical Cord-Derived Mesenchymal Stem Cell-Mediated Rheumatoid Arthritis Therapy.","authors":"Guangyang Liu, Herui Wang, Chenliang Zhang, Xin Li, Yi Mi, Yaoyao Chen, Liqiang Xu, Li Miao, Haomiao Long, Yongjun Liu","doi":"10.1177/09636897241301703","DOIUrl":"10.1177/09636897241301703","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a systemic, chronic inflammatory disease characterized by altered levels of inflammatory cytokines. One of the key cytokines involved in the pathogenesis of RA is tumor necrosis factor α (TNF-α), which plays a crucial role in the differentiation of T cells and B cells and serves as a primary trigger of inflammation and joint damage in RA. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have shown potential in alleviating the symptoms of RA. Previous <i>in vitro</i> studies indicate that TNF-α secreted by T cells can activate NF-κB in human MSCs, thereby triggering the immunoregulatory capacity of MSCs in a manner dependent on tumor necrosis factor receptor 1 (TNFR1). Inspired by these findings, we aimed to evaluate whether TNFR1 determine the therapeutic effects of hUC-MSCs on RA. First, we investigated whether TNFR1 is necessary for hUC-MSCs to inhibit TNF-α production of PBMCs, a source of elevated TNF-α in patients. Through coculture experiment, we confirmed that this inhibition was dependent on TNFR1. Subsequently, we administered hUC-MSCs or siTNFR1-MSCs to DBA/1J male mice with collagen-induced arthritis. The results indicated that hUC-MSCs significantly alleviated the pathological features of RA and suppressed the inflammatory cytokines IFN-γ, TNF-α, and IL-6 in peripheral blood, also in a manner dependent on TNFR1 either. Given the dramatic pathologic differences between hUC-MSCs and siTNFR1-MSCs treatments, we questioned whether production of growth factors and chemokines was significantly influenced by TNFR1. Consequently, we stimulated hUC-MSCs or siTNFR1-MSCs through IFN-γ, TNF-α, and IL-6, and profiled growth factors and chemokines in serum, which revealed significant changes of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF), as well as chemokines CXCL9, CXCL10, IL-8, and RANTES. In summary, our findings suggest that TNFR1 may determine whether hUC-MSCs will gain abilities of anti-inflammation and tissue regeneration.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897241301703"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001073","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":"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":"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}

{"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}