{"title":"A novel approach for hepatocyte transplantation at the liver surface.","authors":"Takumi Katano, Akiko Inagaki, Takehiro Imura, Hiroki Yamana, Ryusuke Saito, Yukiko Endo Kumata, Shoki Suzuki, Yoshiya Hagiwara, Kazuo Ohashi, Kimiko Watanabe, Yasuhiko Tabata, Masafumi Goto","doi":"10.1177/09636897251329308","DOIUrl":"https://doi.org/10.1177/09636897251329308","url":null,"abstract":"<p><p>Hepatocyte transplantation (HTx) is a promising alternative to liver transplantation; however, poor engraftment remains a major challenge. Although co-transplantation with adipose tissue-derived stromal cells (ADSCs) or islets improves engraftment, exposure of these cells to the portal vein enhances innate immune responses, resulting in a significant loss of hepatocytes. Therefore, we investigated HTx at the liver surface as a novel approach that does not involve the portal vein. Hepatocytes were transplanted onto the liver surface of syngeneic analbuminemic rats with or without ADSCs and/or islets. Serum albumin levels and immunohistochemical staining of the transplanted hepatocytes were evaluated. Hepatocyte engraftment was compared between the liver surface and intraportal groups. To examine the detailed mechanisms behind co-transplantation, co-cultured supernatants were analyzed using multiplex assays, and inhibition tests using neutralizing antibodies were performed. Results showed that islet and ADSC co-transplantation markedly enhanced hepatocyte engraftment at the liver surface (<i>P</i> < 0.01), and its efficiency was comparable to that of intraportal transplantation (<i>P</i> = 0.35). In the co-transplantation group, cells were not necessarily in proximity, suggesting that humoral factors are important. In an <i>in vitro</i> study, hepatocyte function was significantly improved by co-culturing with islets and ADSCs (<i>P</i> < 0.01). Multiplex assays and inhibition tests revealed several important humoral factors, most notably insulin, which promoted hepatocyte engraftment. These findings suggest that HTx at the liver surface, together with crucial factors, may be a novel alternative strategy for intraportal transplantation.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251329308"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985581","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":"Comparative analysis of dorsal and tail skin reveals region-dependent heterogeneity in axolotl skin regeneration.","authors":"Lieke Yang, Qian Chen, Jinman Li, Yan Hu, Yaoxin Liu, Binbin Lu, Shuaibin Pei, Tingyi Huang, Yanmei Liu, Ji-Feng Fei","doi":"10.1177/09636897251348730","DOIUrl":"10.1177/09636897251348730","url":null,"abstract":"<p><p>The mechanisms underlying scarless versus fibrotic wound healing remain a critical challenge in regenerative medicine. To elucidate the mechanisms of scarless repair, the axolotl (<i>Ambystoma mexicanum</i>), a model organism with exceptional regenerative capacity, has gained increasing prominence. Although axolotls are capable of regenerating complex structures such as limbs and tails, whether their skin regeneration is uniformly scarless-especially across different anatomical sites-remains undefined. Here, we demonstrate that adult axolotl tail skin achieves scarless regeneration, while dorsal skin repair results in fibrotic scarring. Through comparative histological and transcriptomic analyses of full-thickness excisional wounds, we identify accelerated re-epithelialization and reduced collagen deposition in tail skin compared to dorsal wounds. Developmental trajectory studies reveal prolonged retention of a hypodifferentiated state in tail skin, contrasting with early stratification in dorsal tissue. Mechanistically, we find that the extracellular matrix (ECM) glycoprotein gene <i>Tenascin-N</i> (<i>TnN</i>) exhibits higher expression in tail skin versus dorsal skin. The reported <i>TnN</i> downstream PI3K-Akt signaling pathway, demonstrated by Western blotting of pAkt, is significantly activated in tail skin versus dorsal skin during homeostasis and regeneration. These findings establish the axolotl as a key model for dissecting how developmental priming and ECM dynamics orchestrate regenerative versus fibrotic repair, offering novel insights for therapeutic strategies targeting scarless healing.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251348730"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332529","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":"Donor pigs for clinical islet xenotransplantation: Review and future directions.","authors":"Shinichi Matsumoto, Sadaki Asari, Yoshihide Nanno, Hiroyuki Nakamura, Taisuke Okawa, Takumi Fukumoto","doi":"10.1177/09636897251332532","DOIUrl":"https://doi.org/10.1177/09636897251332532","url":null,"abstract":"<p><p>Allogeneic islet transplantation becomes a viable option for patients with unstable type 1 diabetes. However, considering the huge number of patients with type 1 diabetes, human donor shortage is a serious issue. To overcome the donor shortage issue, xenotransplantation is an attractive option. In fact, clinical islet xenotransplantation has been conducted since 1990s. The first clinical trial was performed using fetal pigs and demonstrated the porcine pancreatic tissue could survive in human body with immunosuppressive strategies. To scale up the islet production, Canadian group established a method for islet isolation from neonatal pigs. Their method has been used for clinical islet xenotransplantation in New Zealand, Russian, Mexico, Argentina, and China. Recently Korean group published a clinical protocol for islet xenotransplantation using adult pigs. For the next generation of islet xenotransplantation, gene-modified pigs were created. Especially \"superislets\" created by Belgian group demonstrated promising preclinical outcomes. With advanced donor pigs, islet xenotransplantation might become a suitable treatment for the majority of type 1 diabetic patients.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251332532"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991101","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}
Cell TransplantationPub Date : 2025-01-01Epub Date: 2025-03-28DOI: 10.1177/09636897251325628
Liqing Jiang, Jie Wang, Yihua Wang, Hang Yang, Lingwang Kong, Zhongjun Wu, Ai Shen, ZuoTian Huang, Yingsong Jiang
{"title":"Bibliometric and LDA analysis of acute rejection in liver transplantation: Emerging trends, immunotherapy challenges, and the role of artificial intelligence.","authors":"Liqing Jiang, Jie Wang, Yihua Wang, Hang Yang, Lingwang Kong, Zhongjun Wu, Ai Shen, ZuoTian Huang, Yingsong Jiang","doi":"10.1177/09636897251325628","DOIUrl":"10.1177/09636897251325628","url":null,"abstract":"<p><p>With the rising demand for liver transplantation (LT), research on acute rejection (AR) has become increasingly diverse, yet no consensus has been reached. This study presents a bibliometric and latent Dirichlet allocation (LDA) topic modeling analysis of AR research in LT, encompassing 1399 articles. The United States, Zhejiang University, and the University of California, San Francisco emerged as leading contributors, while Levitsky J and Uemoto SJ were key researchers. The most influential journals included the <i>American Journal of Transplantation</i>, <i>Journal of Hepatology</i>, and <i>Transplantation</i>. The analysis reveals a transition from traditional histological assessments to molecular diagnostics, genetic and epigenetic profiling, and noninvasive biomarkers such as donor-derived cell-free DNA (dd-cfDNA) and microRNAs. Advances in immune checkpoint inhibitors (ICIs), cell-based therapies (Tregs, mesenchymal stem cells (MSCs)), AI-guided immunosuppression, and nanoparticle-mediated drug delivery systems reflect a growing emphasis on precision medicine. In addition, recent exploration of microbiome-based therapies and regenerative medicine, including MSCs and their extracellular vesicles, offers promising new avenues for reducing long-term immunosuppressive drug dependency and enhancing graft survival. These developments not only improve early AR detection and personalized treatment but also reduce toxicity, foster immune tolerance, and expand the scope of individualized therapeutic options. Global collaboration, supported by cutting-edge research and AI-driven decision-making, remains essential for refining AR strategies, improving graft survival, and achieving better long-term patient outcomes.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251325628"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728888","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":"Anti-Inflammatory Effects of <i>Ex Vivo</i>-Generated Donor Antigen-Specific Immunomodulatory Cells on Pancreatic Islet Transplantation.","authors":"Agustina Forgioni, Masaaki Watanabe, Ryoichi Goto, Takuya Harada, Takuji Ota, Tsuyoshi Shimamura, Akinobu Taketomi","doi":"10.1177/09636897251317887","DOIUrl":"10.1177/09636897251317887","url":null,"abstract":"<p><p>Pancreatic islet transplantation (PITx) is a promising treatment option for patients with type 1 diabetes mellitus. Previously, we demonstrated that therapy with alloantigen-specific immunomodulatory cells (IMCs) generated <i>ex vivo</i> in the presence of anti-CD80 and CD86 monoclonal antibodies (mAbs), successfully induced tolerance following clinical liver transplantation. To extend IMC therapy to PITx, it is crucial to address the strong inflammatory and innate immune responses that occur immediately after PITx. In this study, we investigated the efficacy of IMCs in modulating macrophage activation and mitigating inflammatory damage of pancreatic islets. IMCs were induced using mouse splenocytes in the presence of anti-mouse anti-CD80 (RM80) and anti-CD86 (GL-1) mAbs. IMCs exerted donor-specific immunosuppressive effects in a mixed lymphocyte reaction. During lipopolysaccharide (LPS) stimulation, the addition of IMCs suppressed conversion to the M1 phenotype and promoted a shift toward the M2 phenotype, particularly under direct cell-cell contact conditions. Nitric oxide production, a hallmark of M1 polarized macrophages, was significantly reduced in LPS-stimulated RAW264 macrophages by IMC treatment. These findings were associated with reduced secretion of pro-inflammatory cytokines, tumoral necrosis factor α, and interleukin-6, and increased interleukin-10 production by macrophages. IMCs effectively prevented macrophage-mediated islet destruction after 12 h of co-culture with LPS-stimulated macrophages and significantly inhibited macrophage migration toward allogeneic islets <i>in vitro</i>. Intraportal co-infusion of IMCs with syngeneic islets in a mouse PITx model resulted in reduced messenger RNA (mRNA) expression of pro-inflammatory cytokines in the recipient liver. Immunohistochemical staining revealed a significantly lower number of F4/80+ macrophages at the transplantation site in IMCs-treated mice. These results demonstrate that IMCs modulate macrophage polarization, promoting a shift toward the M2 phenotype and protecting islets from macrophage-mediated damage. These effects combined with its intrinsic donor antigen-specific immunosuppressive capacity make IMC therapy a promising strategy for improving outcomes after PITx.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251317887"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467225","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":"Safe Administration of Immunosuppression in Japanese Monkeys: Relevance to Preclinical Xenotransplantation Studies.","authors":"Naoaki Sakata, Gumpei Yoshimatsu, Ryo Kawakami, Shohta Kodama","doi":"10.1177/09636897251322295","DOIUrl":"10.1177/09636897251322295","url":null,"abstract":"<p><p>The Japanese monkey has been used in several animal studies; however, its potential as a recipient model for xenotransplantation is unclear. The potential of the Japanese monkey as a recipient for xenotransplantation was assessed using two experimental models. The first model evaluated the optimal dose of tacrolimus without severe adverse events. The plasma tacrolimus levels, blood counts, and hepatic and renal function tests were evaluated. The second model assessed the immunosuppressive effects of thymoglobulin and tacrolimus. Immunosuppression was evaluated using blood counts and flow cytometry to measure lymphocytes in peripheral blood mononuclear cells (PBMCs). In the first model, the target trough level (10-15 ng/ml) was achieved and maintained with tacrolimus administration at 1.6 mg/kg/day in all monkeys. There were no adverse events related to the blood count or to liver, kidney, or nutrient parameters at this dose, except for hemoglobin. In the second model, a decrease in white blood cells was observed. Flow cytometry revealed a temporary decrease in T- and B-cell numbers among PBMCs on day 4. We consider that the Japanese monkey is acceptable to be used as a recipient model for preclinical xenotransplantation. The safe administration of tacrolimus and thymoglobulin is clarified for this model.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251322295"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623756","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}
Barbora Hermankova, Eliska Javorkova, Katerina Palacka, Vladimir Holan
{"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}
Cell TransplantationPub Date : 2025-01-01Epub Date: 2025-06-05DOI: 10.1177/09636897251338713
Xin Li, Juan Mu, Jia Wang, Qing Li, Yili Jiang, Jingyi Li, Qi Deng
{"title":"An exploration of the initiation time and patient selection of PD-1 inhibitors/PD-1 inhibitors combined with chemotherapy as salvage therapy in R/R DLBCL patients after anti-CD19-CAR T-cell therapy.","authors":"Xin Li, Juan Mu, Jia Wang, Qing Li, Yili Jiang, Jingyi Li, Qi Deng","doi":"10.1177/09636897251338713","DOIUrl":"10.1177/09636897251338713","url":null,"abstract":"<p><p>A significant proportion of patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) exhibit no response to chimeric antigen receptor (CAR) T-cell therapy or suffer from disease progression thereafter. This study investigated the efficacy and safety of salvage therapy with PD-1 inhibitor-based combination treatment and the patient selection after their CAR T-cell therapy. Twenty-one patients with R/R DLBCL and a high tumor burden were treated with CAR T-cell therapy, a treatment that has shown promising results in clinical trials and has been approved by the Food and Drug Administration (FDA) for use in DLBCL. Patients who achieved complete response (CR) with the CAR T-cell therapy received salvage therapy when their disease progressed again. Patients who obtained partial response (PR) or stable disease (SD) with the CAR T-cell therapy received salvage therapy immediately. Salvage therapy consisted of single PD-1 inhibitors or PD-1 inhibitors combined with chemotherapy. We observed the overall response rate (ORR), overall survival (OS), CAR T-cell amplification, the expression of PD-1, CD3+ T cells, cytokines, and the adverse events. For instance, in a clinical trial of LCAR-B38M CAR T-cell therapy, an 88% ORR was observed, with 74% of patients achieving CR and a median duration of response (DOR) of 16 months. The ORR and CR of the salvage therapy were 28.57% and 19.05%, respectively. The ORR and CR were 38.46% and 30.77% in the 13 patients who achieved PR/SD with the CAR T-cell therapy and received salvage therapy 2 months after CAR T-cell infusion. But the ORR and CR were only 12.5% and 0%, respectively, in patients who achieved CR with the CAR T-cell therapy and received salvage therapy when they experienced disease re-progression. The ratio of CAR-T cells on day 7/day 14 was lower in the PR in CAR-T (effective to PD-1) group. Before salvage therapy, the percentage of CD3+ T cells was higher in the PR in CAR-T (effective to PD-1) group. There was no difference in the Common Terminology Criteria for Adverse Events (CTCAE) grades among the four groups in the salvage therapy. PD-1 inhibitor-based salvage therapy in patients with R/R DLBCL following the CAR T-cell therapy could be an effective and safe treatment, especially in patients who achieved PR after the CAR T-cell therapy and received this salvage therapy immediately.<b>Trial registration number</b>: <i>ChiCTR1800019622 and ChiCTR1900025310</i>.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251338713"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233327","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}