{"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}
Bong-Woo Lee, Jennifer Jooha Lee, Joon-Yong Jung, Ji Hyeon Ju
{"title":"Intra-Articular Injection of Human Bone Marrow-Derived Mesenchymal Stem Cells in Knee Osteoarthritis: A Randomized, Double-Blind, Controlled Trial.","authors":"Bong-Woo Lee, Jennifer Jooha Lee, Joon-Yong Jung, Ji Hyeon Ju","doi":"10.1177/09636897241303275","DOIUrl":"10.1177/09636897241303275","url":null,"abstract":"<p><p>To assess the impact of a single intra-articular (IA) injection of bone marrow-derived mesenchymal stem cells (BM-MSCs) in patients with knee osteoarthritis (OA), a randomized, double-blind, placebo-controlled study was conducted. The study included 24 patients with knee OA who were randomly assigned to receive either a single IA injection of BM-MSCs or normal saline. Changes in the visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Knee Injury and Osteoarthritis Outcome Score (KOOS) after IA injection were assessed at 3, 6, 9, and 12 months. Magnetic resonance imaging (MRI) with T2 mapping sequences was conducted for knee cartilage assessment at baseline and at 3 and 12 months. The MSC group showed between-group improvement in WOMAC (-5.0 ± 3.6 vs. -0.1 ± 5.5, <i>P</i> = 0.02) and KOOS (23.9 ± 18.3 vs. 7.2 ± 15.9, <i>P</i> = 0.028) scores at 9 months compared with the control group. The MSC group exhibited a less sharp increase in the mean T2 value of the medial compartment than the control group at 12 months, with no serious adverse events observed during follow-up. A single IA injection of allogeneic BM-MSCs provided satisfactory pain relief for patients with knee OA compared with the control group at 9 months. Quantitative T2 MRI mapping of the cartilage showed that IA BM-MSCs could have a preventive effect on OA progression for 12 months. Our findings suggest the potential of allogeneic BM-MSCs IA injection as a pain-relieving and disease-modifying treatment for patients with knee OA in the outpatient setting.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897241303275"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057968","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}
Emil Bluhme, Ewa Henckel, Boubou Hallberg, Carl Jorns
{"title":"The Potential of Neonatal Organ Donation in Central Sweden.","authors":"Emil Bluhme, Ewa Henckel, Boubou Hallberg, Carl Jorns","doi":"10.1177/09636897241303269","DOIUrl":"10.1177/09636897241303269","url":null,"abstract":"<p><p>Pediatric organ transplant recipients have a higher risk for wait list mortality due to the scarcity of size matched organs. Neonatal organ donation could potentially ameliorate the discrepancy but is currently not implemented in Sweden. This study aims to evaluate the potential of neonatal organ donation in central Sweden using a standardized protocol with organ specific criteria. Data on 2,061 neonates who deceased in central Sweden from 2006 to 2016 were collected; 308 neonates met criteria for possible donation. Medical records of all possible donors were reviewed, identifying 85 potential donors. Main cause of death was hypoxic ischemic encephalopathy 47% (n = 40). Median weight was 2,355 (IQR: 1,953) g, with 31% receiving inotropic support. Median creatinine of 72 (IQR: 67) µmol/l, urine production 3 (IQR: 2.2) ml/kg/h, ALT 0.51 (IQR: 1.5) µkat/l, and AST 1.7 (IQR: 3.1) µkat/l. Criteria for kidney donation was met in 39 potential neonatal, 29 for liver and 18 for heart, corresponding to a potential increase of 1.9, 1.4, and 0.9 donors PMP per year, respectively. In total, 16 neonates had a catastrophic neurological injury in combination with lack of brainstem reflexes, indicating plausibility of donation after brain death. Expanding organ donation into the neonatal period in Sweden could lead to an increase in organs available for transplant.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897241303269"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037318","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: 2025-08-11DOI: 10.1177/09636897251362107
Xichen Xuan, Xuechun Chu, Ruiliang Wang, Lu Liu, Daqing Li, Pierre Marc Bouloux, Ying Li, Youli Hu
{"title":"Extracellular matrix protein anosmin-1 regulates Schwann cell-astrocyte interaction for regenerative axon targeting in dorsal root crush injury model.","authors":"Xichen Xuan, Xuechun Chu, Ruiliang Wang, Lu Liu, Daqing Li, Pierre Marc Bouloux, Ying Li, Youli Hu","doi":"10.1177/09636897251362107","DOIUrl":"10.1177/09636897251362107","url":null,"abstract":"<p><p>Schwann cell (SC) transplantation is considered as a promising strategy for spinal cord injury. However, SCs show less capability in assisting the regenerative axons to penetrate through astrocyte (AS)-formed scar barrier. Anosmin-1, an extracellular matrix glycosylated adhesion protein expressed in the olfactory bulb, is involved in olfactory ensheathing cells and reborn olfactory nerve axons continually penetrating the glial barrier and targeting the olfactory bulb. In this study, we employ a dorsal root crush injury model treated with anosmin-1. A vertical climbing test was used for behavioral analysis and immunohistochemical study for SC/AS interaction in regenerative axon targeting. Anosmin-1 improved rat forepaw grasping as revealed by forelimb proprioception assessment. After treated with anosmin-1, p75+ immature SCs and P0+ mature SCs mingled well with ASs at the peripheral/central glial interface, reforming the glial barrier from a tight to loose structure. Furthermore, regenerated axons traced by BDA staining revealed proper axonal targeting to the dorsal horn of the spinal cord. These results suggest that anosmin-1 can regulate SC/AS interactions at the peripheral/central boundary site to open the glial barrier for regenerating axons crossing, targeting, and establishing functional neuronal circuits. Anosmin-1 might have a potential application in repair of spinal cord injuries, particularly in combination with SCs for autologous cell transplantation.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251362107"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12340363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815886","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: 2025-09-20DOI: 10.1177/09636897251374203
Mingwei Fu, Siyan Niu, Can Liu, Juan Mu, Shuquan Gao, Gang An, Rui Cui, Qi Deng
{"title":"Correlation between the expression of soluble BCMA and short-term/long-term curative effect and survival outcomes of anti-BCMA CAR-T cell therapy in relapsed/refractory multiple myeloma.","authors":"Mingwei Fu, Siyan Niu, Can Liu, Juan Mu, Shuquan Gao, Gang An, Rui Cui, Qi Deng","doi":"10.1177/09636897251374203","DOIUrl":"10.1177/09636897251374203","url":null,"abstract":"<p><p>This study aimed to investigate whether soluble B-cell maturation antigen (sBCMA) levels could be predictive biomarker for short-term and long-term therapeutic efficacy and survival outcomes following anti-BCMA CAR-T cell therapy in relapsed/refractory multiple myeloma (R/R MM). We enrolled 29 R/R MM patients who received anti-BCMA CAR-T cell therapy. In short-term observation, proportion of MM cells, expression of B-cell maturation antigen (BCMA) and sBCMA in bone marrow (BM) were evaluated, along with adverse events, correlation between sBCMA levels and short-term efficacy or survival outcomes were evaluated. In long-term observation, expressions of sBCMA were observed up to 24 months after therapy or until disease progression again in patients who achieved an objective response (ORR). Progression-free survival (PFS), overall survival (OS), correlation between sBCMA levels, and long-term outcomes were analyzed. In short-term observation, high expressions of sBCMA in BM were associated with poor efficacy of CAR-T cell therapy, while the proportion of MM cells in BM and BCMA expression in MM cells were not associated with poor efficacy of therapy. After 2 months of infusion, sBCMA levels decreased significantly, especially in patients who obtained ORR. In long-term follow-up, for patients who achieved ORR, the sBCMA levels significantly increased again when their disease progressed once more. Notably, R/R MM patients with extramedullary disease (EMD) demonstrated a higher likelihood of disease progression again. In patients achieved ORR, peaks of CAR-T cells correlated with proportion of MM cells, not with BCMA and sBCMA expression. Additionally, sBCMA levels were independent of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) severity. We suggest that sBCMA levels in BM might serve as a predictive biomarker for anti-BCMA CAR-T cell therapy efficacy prior to treatment and for disease progression during long-term monitoring. The trail register name is China Clinical Trial Register. URL are https://www.chictr.org.cn/bin/project/edit?pid=28999 and https://www.chictr.org.cn/bin/project/edit?pid=53962. Registration numbers are <i>ChiCTR1800017051</i> and <i>ChiCTR2000033925</i>.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251374203"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091295","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}
Xiaoping Li, Yu Li, Dingsong Zhang, Xiaozhuang Hu, Lin Liu, Zhongtao Yuan, Shiqi Li, Yancheng Dong, Yingnian Chen, Sanbin Wang
{"title":"The Combination of Intravenous Immunoglobulin, Dexamethasone, and a High Dose of Mononuclear Cells Transfusion: An Effective Strategy for Decreasing Donor-Specific Antibodies During Haploidentical Hematopoietic Stem Cell Transplantation.","authors":"Xiaoping Li, Yu Li, Dingsong Zhang, Xiaozhuang Hu, Lin Liu, Zhongtao Yuan, Shiqi Li, Yancheng Dong, Yingnian Chen, Sanbin Wang","doi":"10.1177/09636897241303292","DOIUrl":"10.1177/09636897241303292","url":null,"abstract":"<p><p>Donor-specific antibodies (DSAs) are essential causes of graft rejection in haploidentical hematopoietic stem cell transplantation (haplo-HSCT). DSAs are unavoidable for some patients who have no alternative donor. Effective interventions to reduce DSAs are still needed, and the cost of the current therapies is relatively high. In this study, we retrospectively analyzed the data of 11 DSA-positive patients who received haplo-HSCT at our center and evaluated the therapeutic efficacy of the combination of intravenous immunoglobulin (IVIG), dexamethasone and high dose of transfused mononuclear cells (MNCs) for DSA desensitization. The kinetics of DSAs at different times and the engraftment and transplantation outcomes were also observed. We found that all patients had successful donor-cell engraftment and that no patient developed poor graft function. The median engraftment times of neutrophils and platelets were 14 days (range, 11-24 days) and 13 days (range, 11-123 days), respectively. The DSA levels of all patients became negative or dropped under 2000 within 22 days after HSCT. A total of 36.4% of patients developed grade II-IV acute graft-versus-host disease (aGVHD), and 9.1% of patients died of severe gastrointestinal aGVHD. Of the 7 surviving patients, four were diagnosed with chronic GVHD. After a median follow-up of 28.9 months (2.0-52.1 months), four patients died: of relapse (two), aGVHD (one), and multiple-organ failure (one). The 2-year OS, DFS, and NRM were 63.6%, 45.4%, and 18.2%, respectively. Combination therapy with IVIG, dexamethasone, and a high dose of MNCs transfusion, a simple and efficient procedure, was safe and effective for DSA desensitization and peripheral blood stem cell (PBSC) engraftment.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897241303292"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051812","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: 2025-06-25DOI: 10.1177/09636897251348566
Kentaro Nakamura
{"title":"Key mediators of the efficacy of mesenchymal stem cells on <i>in vivo</i> disease models.","authors":"Kentaro Nakamura","doi":"10.1177/09636897251348566","DOIUrl":"10.1177/09636897251348566","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) are considered to be effective treatments for various diseases, and a wide variety of clinical studies have been performed worldwide. However, substantial obstacles remain before they can be approved and disseminated as treatments. A major bottleneck is the elucidation of their mechanisms of action, and the molecules that are essential for their efficacy have not been fully characterized. In this paper, I review the studies that attempted to identify the key mediators of MSCs that are involved in their effects on disease using <i>in vivo</i> models. More specifically, studies are discussed in which reductions in the efficacy of MSCs in animal models of disease were induced by the absence of key mediators. The target diseases were lung, joint, cerebral nerve, or cardiac diseases and graft-versus-host disease (GVHD). The following molecules were identified and are discussed herein: TSG-6, VEGF, KGF, HGF, claudin-4, ANXA1, MANF, PYCR1, integrin β1, PDGFRβ, type-II collagen, CD151, TIMP3, TGF-β1, BDNF, COX-2, Botch, IL-1β, CTRP3, CXCR4, miR-34c, FSTL1, IDO, iNOS, IFNγR1, PGES, Chi3l1, and IL-6. These are key mediators of the efficacy of MSCs <i>in vivo</i>.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"34 ","pages":"9636897251348566"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483200","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}