{"title":"Safety and Tolerability of Intra-Articular Injection of Adipose-Derived Mesenchymal Stem Cells GXCPC1 in 11 Subjects With Knee Osteoarthritis: A Nonrandomized Pilot Study Without a Control Arm.","authors":"Cheng-Fong Chen, Yi-Chung Chen, Yu-Show Fu, Shang-Wen Tsai, Po-Kuei Wu, Chao-Ming Chen, Wei-Ming Chen, Hung-Ta Hondar Wu, Chia-Hsin Lee, Chao-Liang Chang, Po-Cheng Lin, Yong-Cheng Kao, Chun-Hung Chen, Ming-Hsi Chuang","doi":"10.1177/09636897231221882","DOIUrl":"10.1177/09636897231221882","url":null,"abstract":"<p><p>The current study aimed to determine the safety profile of intra-articular-injected allogeneic adipose-derived mesenchymal stem cells (ADSCs) GXCPC1 in subjects with knee osteoarthritis (OA) and its preliminary efficacy outcome. The 3 + 3 phase I study was designed with two dose-escalation cohorts: low dose (6.7 × 10<sup>6</sup> GXCPC1, <i>N</i> = 5) and high dose (4 × 10<sup>7</sup> GXCPC1, <i>N</i> = 6). The primary endpoint was safety, which was evaluated by recording adverse events throughout the trial; the secondary endpoints included total, pain, stiffness, and function subscales of the Western Ontario and McMaster Universities Arthritis Index (WOMAC), Visual Analogue Scale (VAS) for pain, and 12-Item Short Form (SF-12) health survey questionnaire. The GXCPC1 treatment was found to be safe after 1 year of follow-up with no treatment-related severe adverse events observed. When compared to baseline, subjects in both the low- and high-dose cohorts demonstrated improving trends in pain and knee function after receiving GXCPC1 treatment. Generally, the net change in pain (95% confidence interval (CI) = -7.773 to -2.561t at 12 weeks compared to baseline) and knee function (95% CI = -24.297 to -10.036t at 12 weeks compared to baseline) was better in subjects receiving high-dose GXCPC1. Although this study included a limited number of subjects without a placebo arm, it showed that the intra-articular injection of ADSCs was safe and well-tolerated in subjects with therapeutic alternatives to treat knee OA. However, a larger scale study with an appropriate control would be necessary for clinical efficacy in the following study.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897231221882"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10785714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416444","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}
Maria Alvarez-Viejo, Luis Romero-Rosal, Marcos Perez-Basterrechea, Jose M García-Gala, Pablo Hernando-Rodriguez, Jesus Marana-Gonzalez, Miriam Rubiera-Valdes, Blanca Vivanco-Allende, Angeles Fernandez-Rodriguez, Eva Martinez-Revuelta, Silvia Perez-Lopez
{"title":"Plasma-Based Scaffold Containing Bone-Marrow Mononuclear Cells Promotes Wound Healing in a Mouse Model of Pressure Injury.","authors":"Maria Alvarez-Viejo, Luis Romero-Rosal, Marcos Perez-Basterrechea, Jose M García-Gala, Pablo Hernando-Rodriguez, Jesus Marana-Gonzalez, Miriam Rubiera-Valdes, Blanca Vivanco-Allende, Angeles Fernandez-Rodriguez, Eva Martinez-Revuelta, Silvia Perez-Lopez","doi":"10.1177/09636897241251619","DOIUrl":"10.1177/09636897241251619","url":null,"abstract":"<p><p>Pressure injuries, or pressure ulcers, are a common problem that may lead to infections and major complications, besides being a social and economic burden due to the costs of treatment and hospitalization. While surgery is sometimes necessary, this also has complications such as recurrence or wound dehiscence. Among the newer methods of pressure injury treatment, advanced therapies are an interesting option. This study examines the healing properties of bone marrow mononuclear cells (BM-MNCs) embedded in a plasma-based scaffold in a mouse model. Pressure ulcers were created on the backs of mice (2 per mouse) using magnets and assigned to a group of ulcers that were left untreated (Control, n = 15), treated with plasma scaffold (Plasma, n = 15), or treated with plasma scaffold containing BM-MNC (Plasma + BM-MNC, n = 15). Each group was examined at three time points (3, 7, and 14 days) after the onset of treatment. At each time point, animals were subjected to biometric assessment, bioluminescence imaging, and tomography. Once treatment had finished, skin biopsies were processed for histological and wound healing reverse transcription polymerase chain reaction (RT-PCR) array studies. While wound closure percentages were higher in the Plasma and Plasma + BM-MNC groups, differences were not significant, and thus descriptive data are provided. In all individuals, the presence of donor cells was revealed by immunohistochemistry on posttreatment onset Days 3, 7, and 14. In the Plasma + BM-MNC group, less inflammation was observed by positron emission tomography-computed tomography (PET/CT) imaging of the mice at 7 days, and a complete morphometabolic response was produced at 14 days, in accordance with histological results. A much more pronounced inflammatory process was observed in controls than in the other two groups, and this persisted until Day 14 after treatment onset. RT-PCR array gene expression patterns were also found to vary significantly, with the greatest difference noted between both treatments at 14 days when 11 genes were differentially expressed.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241251619"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11102697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956086","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}
Zhenyang Gu, Fei Li, Meng Li, Linlin Zhang, Sai Xu, Lu Wang, Lili Wang, Yu Jing, Jian Bo, Chunji Gao, Liping Dou, Daihong Liu
{"title":"Similar Survival But Less Chronic GVHD in Antithymocyte Globulin-Based Myeloablative Haploidentical Transplant Compared With Matched Sibling Transplant for Adult T-cell Acute Lymphoblastic Leukemia/Lymphoma.","authors":"Zhenyang Gu, Fei Li, Meng Li, Linlin Zhang, Sai Xu, Lu Wang, Lili Wang, Yu Jing, Jian Bo, Chunji Gao, Liping Dou, Daihong Liu","doi":"10.1177/09636897241270401","DOIUrl":"10.1177/09636897241270401","url":null,"abstract":"<p><p>The annual number of human leukocyte antigen (HLA)-haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HCT) is increasing steadily. Comparative studies about haplo-HCT versus HCT with HLA-matched sibling donors (MSD-HCT) have been tried in acute myeloid leukemia and B-cell acute lymphoblastic leukemia/lymphoma (ALL). Few studies were reported in adult T-cell ALL (T-ALL). In this retrospective study, a total of 88 consecutive patients with T-ALL were enrolled who underwent MSD-HCT (<i>n</i> = 24) and haplo-HCT (<i>n</i> = 64) with antithymocyte globulin (ATG)-based graft versus host disease (GVHD) prophylaxis between 2010 and 2022. Median follow-up for survivors was similar (43.5 [range: 7-88] months for MSD-HCT versus 43.5 (range: 6-144) months in the Haplo-HCT group). The 100-day cumulative incidence of grade II to IV acute GVHD (aGVHD) was similar, 33% (95% confidence interval [CI], 16%-52%) after MSD-HCT versus 44% (95% CI, 31%-55%) after haplo-HCT, <i>P</i> = 0.52. The cumulative incidences of grade III-IV aGVHD were 8% (95% CI, 1%-23%) in the MSD-HCT group and 5% (95% CI, 1%-12%) in the haplo-HCT group (<i>P</i> = 0.50). The 2-year cumulative incidence of chronic GVHD (limited and extensive) in the haplo-HCT, 11% (95% CI, 5%-20%) was significantly lower than that in the MSD-HCT group (42% [95% CI, 21%-62%], <i>P</i> = 0.002). The cumulative incidence of 4-year relapse rates (44% versus 37%, <i>P</i> = 0.56) and non-relapse mortality (7% versus 21%, <i>P</i> = 0.08) did not differ between these two groups. There were also no differences in 4-year overall survival (46% versus 47%, <i>P</i> = 0.44) and progression-free survival (49% versus 42%, <i>P</i> = 0.45) between these two groups. On multivariate analysis, using busulfan/fludarabine (BU/Flu) conditioning regimen was found to be associated with worse clinical outcome. Our results suggested that ATG-based haplo-HCT platform could work as an alternative to MSD-HCT for adult patients with T-ALL. Compared with MSD-HCT, haplo-HCT might carry a low risk for cGVHD.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241270401"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104688","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":"Ovarian Cancer Patient-Derived Organoids Used as a Model for Replicating Genetic Characteristics and Testing Drug Responsiveness: A Preliminary Study.","authors":"Yu-Hsun Chang, Kun-Chi Wu, Kai-Hung Wang, Dah-Ching Ding","doi":"10.1177/09636897241281869","DOIUrl":"https://doi.org/10.1177/09636897241281869","url":null,"abstract":"<p><p>This study aimed to explore the role of ovarian cancer patient-derived organoids (PDOs) in their replicating genetic characteristics and testing drug responsiveness. Ovarian cancer PDOs were cultured in Matrigel with a specialized medium. The successful rate and proliferation rate were calculated. Morphology, histology, and immunohistochemistry (IHC) (PAX8, P53, and WT1) were used to identify the tumor characteristics. Gene sequencing, variant allele frequency (VAF), and copy number variation were used to explore the mutation profile. The sensitivity to chemodrugs (carboplatin, paclitaxel, gemcitabine, doxorubicin, and olaparib) was conducted. Successful generation of organoids occurred in 54% (7/13) of attempts, encompassing 4 high-grade serous carcinomas (HGSC), 1 mucinous carcinoma (MC), 1 clear cell carcinoma (CCC), and 1 carcinosarcoma. The experiments used six organoids (3 HGSC, 1 CCC, 1 MC, and 1 carcinosarcoma). The derived organoids exhibited spherical-like morphology, and the diameter ranged from 100 to 500 μm. The histology and IHC exhibited the same between organoids and primary tumors. After cryopreservation, the organoid's growth rate was slower than the primary culture (14 days vs 10 days, <i>P</i> < 0.01). Targeted sequencing revealed shared DNA variants, including mutations in key genes, such as <i>BRCA1</i>, <i>PIK3CA, ARID1A</i>, and <i>TP53</i>. VAF was similar between primary tumors and organoids. The organoids maintained inherited most copy number alterations. Drug sensitivity testing revealed varying responses, with carcinosarcoma organoids showing higher sensitivity to paclitaxel and gemcitabine than HGSC organoids. Our preliminary results showed that ovarian cancer PDOs could be successfully derived and histology, mutations, and diverse copy numbers of genotypes could be faithfully captured. Drug testing could reveal the individual PDO's responsiveness to drugs. PDOs might be as valuable resources for investigating genomic biomarkers for personalized treatment.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241281869"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11425734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342457","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":"Olfactory Ensheathing Cell Ameliorate Neuroinflammation Following Spinal Cord Injury Through Upregulating REV-ERBα in Microglia.","authors":"Lijian Zhang, Luxuan Wang, Yanli Tan, Chunhui Li, Chuan Fang","doi":"10.1177/09636897241261234","DOIUrl":"10.1177/09636897241261234","url":null,"abstract":"<p><p>Circadian dysregulation involved in the pathophysiology of spinal cord injury (SCI). Modulation of circadian rhythms hold promise for the SCI treatment. Here, we aim to investigated the mechanism of olfactory ensheathing cells (OEC) in alleviating neuroinflammation via modulating clock gene expression in microglia. In this study, SCI rats were randomly divided into OEC group and vehicle group. At 1 day after the surgery, OECs were intravenously transplanted into OEC group SCI rat, while the rats in vehicle group received culture medium. After 7 days post of OEC transplantation, tissues were collected from the brain (prefrontal cortex, hypothalamus, spinal cord) for PCR, western blotting and immunohistochemistry (IHC) assay at zeitgeber time (ZT) 6, ZT 12, ZT 18, and ZT 24. The roles of OEC in modulating REV-ERBα in microglia were studied by experimental inhibition of gene expression and the co-culture experiment. In the vehicle group, IHC showed a significant increase of Iba-1 expression in the cerebral white matter and spinal cord compared with control group (<i>P</i> < 0.0001 for all comparisons). The expression of Iba-1 was significantly decreased (<i>P</i> < 0.0001 for all comparisons). In the OEC group, the expression of PER 1, PER 2, CLOCK, and REV-ERBα was in a rhythmical manner in both spinal cord and brain regions. SCI disrupted their typical rhythms. And OECs transplantation could modulate those dysregulations by upregulating REV-ERBα. In vitro study showed that OECs couldn't reduce the activation of REV-ERBα inhibited microglia. The intravenous transplantation of OECs can mediate cerebral and spinal microglia activation through upregulation REV-ERBα after SCI.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241261234"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787276","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":"Retraction Notice: Neurospheres Induced from Human Adipose-Derived Stem Cells as a New Source of Neural Progenitor Cells.","authors":"","doi":"10.1177/09636897241265808","DOIUrl":"10.1177/09636897241265808","url":null,"abstract":"","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241265808"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11292709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854868","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}
Jodi Scholz, Frank J Secreto, Joan Wobig, Joe Kurian, Clint Hagen, Alexandra Zinnen, Don Vu, Steven J Johnson, Frank Cetta, Yasir Qureshi, Rachel Reams, Bryan Cannon, Christina M Heyer, Minhwang Chang, Numrah Fadra, Jennifer Coonen, Heather A Simmons, Andres Mejia, Jennifer M Hayes, Puja Basu, Saverio Capuano, Viktoriya Bondarenko, Jeanette M Metzger, Timothy J Nelson, Marina E Emborg
{"title":"Human Stem Cell-Derived Cardiomyocytes Integrate Into the Heart of Monkeys With Right Ventricular Pressure Overload.","authors":"Jodi Scholz, Frank J Secreto, Joan Wobig, Joe Kurian, Clint Hagen, Alexandra Zinnen, Don Vu, Steven J Johnson, Frank Cetta, Yasir Qureshi, Rachel Reams, Bryan Cannon, Christina M Heyer, Minhwang Chang, Numrah Fadra, Jennifer Coonen, Heather A Simmons, Andres Mejia, Jennifer M Hayes, Puja Basu, Saverio Capuano, Viktoriya Bondarenko, Jeanette M Metzger, Timothy J Nelson, Marina E Emborg","doi":"10.1177/09636897241290367","DOIUrl":"10.1177/09636897241290367","url":null,"abstract":"<p><p>Cardiac ventricular pressure overload affects patients with congenital heart defects and can cause cardiac insufficiency. Grafts of stem cell-derived cardiomyocytes are proposed as a complementary treatment to surgical repair of the cardiac defect, aiming to support ventricular function. Here, we report successful engraftment of human induced pluripotent stem cell-derived cardiac lineage cells into the heart of immunosuppressed rhesus macaques with a novel surgical model of right ventricular pressure overload. The human troponin+ grafts were detected in low-dose (2 × 10<sup>6</sup> cells/kg) and high-dose (10 × 10<sup>6</sup> cells/kg) treatment groups up to 12 weeks post-injection. Transplanted cells integrated and progressively matched the organization of the surrounding host myocardium. Ventricular tachycardia occurred in five out of 16 animals receiving cells, with episodes of incessant tachycardia observed in two animals; ventricular tachycardia events resolved within 19 days. Our results demonstrate that grafted cardiomyocytes mature and integrate into the myocardium of nonhuman primates modeling right ventricular pressure overload.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241290367"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564100","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":"YTHDC1 Mitigates Apoptosis in Bone Marrow Mesenchymal Stem Cells by Inhibiting <i>NfƙBiα</i> and Augmenting Cardiac Function Following Myocardial Infarction.","authors":"Weiyu Han, Weidong Xiong, Weixing Sun, Weiwei Liu, Yu Zhang, Chaofu Li, Ning Gu, Youcheng Shen, Zhimei Qiu, Chaozhong Li, Yongchao Zhao, Ranzun Zhao","doi":"10.1177/09636897241290910","DOIUrl":"10.1177/09636897241290910","url":null,"abstract":"<p><p>The therapeutic efficacy of bone marrow mesenchymal stem cells (BMSCs) in myocardial infarction (MI) is hindered by poor cell survival. This study explored the role of N6-methyladenosine (m6A) regulation, specifically YTHDC1, in improving BMSC transplantation for MI. By screening m6A-related regulators in hypoxia and serum deprivation (HSD)-induced BMSC apoptosis, YTHDC1 was found to be downregulated. Overexpression of Ythdc1 in BMSCs reduced apoptosis markers, reactive oxygen species (ROS) release, and improved cell survival under HSD conditions. Conversely, Ythdc1 knockdown enhanced apoptosis. In rat MI models, transplantation of Ythdc1-overexpressing BMSCs improved cardiac function and reduced myocardial fibrosis. Mechanistically, YTHDC1 interacts with nuclear factor kappa B (NF-κB) inhibitor-alpha mRNA, suggesting its involvement in BMSC survival pathways. This study identifies YTHDC1 as a potential target to enhance BMSC efficacy in MI therapy.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241290910"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CAR-T-Cell Therapy Based on Immune Checkpoint Modulation in the Treatment of Hematologic Malignancies.","authors":"Manqi Su, Zhanna Zhang, Panruo Jiang, Xiaoxia Wang, Xiangmin Tong, Gongqiang Wu","doi":"10.1177/09636897241293964","DOIUrl":"10.1177/09636897241293964","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T-cell therapy is a revolutionary immunotherapy that has shown significant success in treating certain hematologic malignancies. However, there are still challenges and limitations associated with this therapy, and not all cancer patients benefit from this therapy alone. Therefore, modifying CAR-T-cell therapy based on immune checkpoints, and its combination with immune checkpoint inhibitors (ICIs), shows promise as a potentially more effective strategy for treating hematologic malignancies. This article outlines the progress of preclinical and clinical trials of CAR-T-cell therapy based on immune checkpoint modulation in the treatment of hematologic malignancies.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241293964"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ming Yao, Jarmo Henriksson, Henrik Fahlander, Pablo Guisti Coitinho, Torbjörn Lundgren, Nils Ågren, Bo-Göran Ericzon, Makiko Kumagai-Braesch
{"title":"Evaluation of Methods to Obtain Peripheral Blood Mononuclear Cells From Deceased Donors for Tolerance-Induction Protocols.","authors":"Ming Yao, Jarmo Henriksson, Henrik Fahlander, Pablo Guisti Coitinho, Torbjörn Lundgren, Nils Ågren, Bo-Göran Ericzon, Makiko Kumagai-Braesch","doi":"10.1177/09636897241256462","DOIUrl":"10.1177/09636897241256462","url":null,"abstract":"<p><p>Regulatory cell therapies have shown promise in tolerance-induction protocols in living donor organ transplantation. These protocols should be pursued in deceased donor transplantation. Donor peripheral mononuclear cells (PBMCs) are an optimal source of donor antigens for the induction of donor-specific regulatory cells. During the development of a regulatory cell tolerance-induction protocol with organs from deceased donors, we compared 3 methods of obtaining PBMCs from deceased donors focusing on cell yield, viability, and contamination of unwanted cell types. PBMC procurement methods: 1. During organ procurement at the time of cold perfusion, blood was collected from the vena cava and placed into a 10-liter blood collection bag, and thereafter transported to Karolinska University Hospital, where leukapheresis was performed (BCL). 2. Blood was collected via the vena cava into blood donation bags before cold perfusion. The bags underwent buffy coat separation and thereafter automated leukocyte isolation system (BCS). 3. To collect PBMCs, leukapheresis was performed via a central dialysis catheter on deceased donors in the intensive care unit (ICU) prior to the organ procurement procedure (LEU).All 3 methods to obtain PBMC from deceased donors were safe and did not affect the procurement of organs. BCL contained around 50% of NK cells in lymphocytes population. LEU had a highest yield of donor PBMC among 3 groups. LEU had the lower amount of granulocyte contamination, compared to BCS and BCL. Based on these results, we choose LEU as the preferred method to obtain donor PBMC in the development of our tolerance-induction protocol.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241256462"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161480","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}