Cytotherapy最新文献

{"title":"Acute respiratory distress vs healthy lung environments differently affect mesenchymal stromal cell extracellular vesicle miRNAs.","authors":"Sara Rolandsson Enes, Irakli Dzneladze, Thomas H Hampton, Samuel L Neff, Lori Asarian, Jayita Barua, Tobias Tertel, Bernd Giebel, Nicolas Pereyra, David H McKenna, Pingzhao Hu, Erica Acton, Alix Ashare, Kathleen D Liu, Anna D Krasnodembskaya, Karen English, Bruce A Stanton, Patricia R M Rocco, Michael A Matthay, Claudia C Dos Santos, Daniel J Weiss","doi":"10.1016/j.jcyt.2025.01.006","DOIUrl":"https://doi.org/10.1016/j.jcyt.2025.01.006","url":null,"abstract":"<p><p>The acute respiratory distress syndrome (ARDS) inflammatory environment alters mesenchymal stromal cell (MSC) gene and protein expression but effects on microRNA (miRNA) content of MSC-extracellular vesicle (EVs) remain unknown. To assess this, sequencing analysis of EV-miRNAs prepared from human bone marrow-derived MSCs (hMSCs) exposed ex vivo to bronchoalveolar lavage fluid (BALF) from ARDS patients or healthy volunteers (HV) identified a number of differentially expressed miRNAs. Discriminant, differential expression, and functional enrichment analyses identified 14 miRNAs significantly changed following ARDS versus HV BALF exposure. Network analysis showed 4 (miR-760, miR-3175, miR-885-3p, and miR-766-3p) of the 14 EV-miRNAs formed a regulatory \"hub\", suggesting co-targeting of specific gene pathways. In silico prediction identified a number of pathways important in lung injury. Two miRNAs involved in regulation of the cystic fibrosis transmembrane conductance regulator (CFTR), miRNA-145-5p and miRNA-138-5p, were also significantly increased in ARDS BALF-exposed hMSCs EVs. Functionally, EVs from hMSCs exposed to either ARDS or HV BALF had differential effects on CFTR Cl^- secretion by cultured primary human bronchial epithelial cells, an effect predicted to reduce mucociliary clearance. The potential clinical impact of these finding highlights the need for further studies assessing the role of hMSC-EV miRNAs in regulating lung inflammation and mucociliary clearance.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human cornea-derived mesenchymal stromal cells inhibit T cells through indoleamine 2,3 dioxygenase.","authors":"Tyler U Faircloth, Sara Temple, Rhett Parr, Alyssa Soma, Hamed Massoumi, Elmira Jalilian, Ali R Djalilian, Peiman Hematti, Devi Rajan, Raghavan Chinnadurai","doi":"10.1016/j.jcyt.2025.01.009","DOIUrl":"https://doi.org/10.1016/j.jcyt.2025.01.009","url":null,"abstract":"<p><p>Defining the mechanism of immune modulation by mesenchymal stromal cells (MSCs) from distinct anatomical tissues is of great translational interest. The human cornea is an immunologically privileged organ, and the mechanism of immunoregulation of cornea-derived MSCs (cMSCs) is currently unknown. We investigated cMSCs derived from the corneas of 5 independent human donorS for their fitness and mechanism of action in suppressing T cells. cMSCs display the immunophenotype CD45-CD73+CD105+CD90+CD44+ and robust in vitro growth. 30-plex secretome analysis identified that cMSCs innately secrete specific molecules in a dose-dependent manner. cMSCs do not express or upregulate costimulatory but do upregulate coinhibitory molecules upon stimulation with interferon γ (IFNγ). cMSCs inhibit T-cell proliferation in contact-dependent co-cultures, which can be predicted by a unique secretome signature. In addition, co-culturing in a 2-chamber transwell system has demonstrated that cMSCs also inhibit T-cell proliferation in a non-contact-dependent manner. Mechanistic analysis has demonstrated that activated T cells effectively induce indoleamine 2,3-dioxygenase (IDO) but not other enzymes of the tryptophan metabolic pathway in cMSCs. Silencing of IDO in cMSCs reduces their fitness to suppress T cells. These results provide evidence that in cMSCs, one of the principal mechanisms of immunosuppression on T cells is through IDO. These results suggest that MSCs derived from the human cornea display immunoregulatory properties and, thus, may play a role in maintaining the immune-privileged niche of the cornea.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ISCT MSC committee statement on the US FDA approval of allogenic bone-marrow mesenchymal stromal cells","authors":"Katarina Le Blanc ,&nbsp;Francesco Dazzi ,&nbsp;Karen English ,&nbsp;Dominique Farge ,&nbsp;Jacques Galipeau ,&nbsp;Edwin M. Horwitz ,&nbsp;Nadir Kadri ,&nbsp;Mauro Krampera ,&nbsp;Manoj Mathew Lalu ,&nbsp;Jan Nolta ,&nbsp;Nikita M. Patel ,&nbsp;Yufang Shi ,&nbsp;Daniel J. Weiss ,&nbsp;Sowmya Viswanathan","doi":"10.1016/j.jcyt.2025.01.005","DOIUrl":"10.1016/j.jcyt.2025.01.005","url":null,"abstract":"<div><div>The December 2024 US Food and Drug Administration (FDA) approval of Mesoblast's Ryoncil (remestemcel-L-rknd)—allogeneic bone marrow mesenchymal stromal cell (MSC(M)) therapy—in pediatric acute steroid-refractory graft-versus-host-disease finally ended a long-lasting drought on approved MSC clinical products in the United States. While other jurisdictions—including Europe, Japan, India, and South Korea—have marketed autologous or allogeneic MSC products, the United States has lagged in its approval. The sponsor's significant efforts and investments, working closely with the FDA addressing concerns regarding clinical efficacy and consistent MSC potency through an iterative process that spanned several years, was rewarded with this landmark approval. This approval will revive investment and enthusiasm in MSC products, further approvals in major markets, and will continue to foreshadow the long-predicted success of MSCs as a pharmaceutical.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 4","pages":"Pages 413-416"},"PeriodicalIF":3.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigating workforce needs in the field of cell and gene therapy: results of workforce survey performed by the ISCT early-stage professionals committee","authors":"Theodros Mamo ,&nbsp;Arwa Z. Al-Riyami ,&nbsp;Pedro Silva Couto ,&nbsp;Ben Weil","doi":"10.1016/j.jcyt.2024.12.012","DOIUrl":"10.1016/j.jcyt.2024.12.012","url":null,"abstract":"<div><h3>Background and aim</h3><div>The workforce landscape in the field of cell and gene therapy (CGT) continues to evolve. As new therapies receive approval and numerous clinical trials are underway, there is an increasing demand to understand training and career development within the CGT sector. The International Society of CGT (ISCT) early-stage professionals (ESP) committee has been conducting workforce surveys to understand the existing skillset of CGT professionals, including ESP, and to highlight critical areas where training programs may be required. Here, we report the findings of these muti-year workforce surveys.</div></div><div><h3>Methods</h3><div>The survey was designed by ESP committee members and distributed primarily to ISCT members and the Canadian CellCAN network, mainly targeting ESPs (those within 10 years of their final degree or entry into the CGT field). The 2020 and 2021 surveys consisted of 19 questions covering respondents’ educational background, demographics, employment status, employment sector and participation in continuing education. In 2023, the survey was expanded to include an additional 8 qualitative questions focusing on career development opinions and opportunities. The number of respondents was 58 in 2020, 61 in 2021 and 109 in 2023. Trends and summaries of the results over the 3 years are reported here.</div></div><div><h3>Results</h3><div>Manufacturing and process development were the most common job roles, as well as the most desired skills and the biggest workforce gap in the CGT sector. Over the 3 years, the percentage of respondents in managerial roles increased while those working in a Good Manufacturing Practice environment decreased. On the other hand, the percentage of respondents with an MS degree decreased, while those with a PhD degree showed an overall increase from 2020 to 2021 with a slight decrease in 2023. Finally, participants concluded that the lack of available positions as well as the lack of opportunities or support are the key hindrances in their career development.</div></div><div><h3>Conclusions</h3><div>Collecting data to evaluate the workforce and training remains an important venture in the CGT field. Our survey showed that manufacturing and process development roles are in great demand, suggesting the need for continued workforce training of this critical need. The trends observed through the survey years also suggest a possible effect of the COVID-19 pandemic on the CGT workforce, which may have stabilized since 2023. Overall, our survey shows that there is a need to address the workforce gap while also paying attention to the career development of those aspiring to join the CGT workforce.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 4","pages":"Pages 417-421"},"PeriodicalIF":3.7,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Robust differentiation and potent immunomodulation of human mesenchymal stromal cells cultured with a xeno-free GMP protein supplement","authors":"Irene Oliver-Vila ,&nbsp;Eduardo Sesma-Herrero ,&nbsp;Francisco Belda ,&nbsp;Anna Seriola ,&nbsp;Samuel Ojosnegros","doi":"10.1016/j.jcyt.2025.01.003","DOIUrl":"10.1016/j.jcyt.2025.01.003","url":null,"abstract":"<div><h3>Background/Aims</h3><div>Human mesenchymal stromal cells (hMSC) are multipotent adult cells commonly used in regenerative medicine as advanced therapy medicinal products. The expansion of these cells in xeno-free supplements is highly encouraged by regulatory agencies due to safety concerns. However, the number of supplements with robust performance and consistency for hMSC expansion are limited. Here, we evaluate a xeno-free human plasma-derived protein supplement (Plastem, Grifols) for the expansion and functional evaluation of hMSCs.</div></div><div><h3>Methods</h3><div>hMSC from bone marrow, adipose tissue and umbilical cord were obtained from two suppliers and cultured in Dulbecco's modified Eagle's medium (DMEM/F-12) supplemented with fetal bovine serum 10% (FBS), human platelet lysate 5% (hPL) or Plastem 10%+ hPL0.5%. Cell proliferation was evaluated after culturing hMSC for 13 days with trypan blue exclusion. hMSC immunophenotype was assessed by flow cytometry of surface markers expression. Multipotentiality assay determined the ability of hMSC to differentiate into osteogenic, chondrogenic and adipogenic lineages after 21 days, by using specific staining. Immunomodulatory properties of hMSC were analyzed by measuring suppression of human peripheral blood mononuclear cell (PBMC) proliferation in co-culture with hMSC.</div></div><div><h3>Results</h3><div>Plastem 10% + hPL 0.5% supported robust and sustained hMSC growth with a similar efficiency to the reference supplement FBS 10%. hMSC cultured with the xeno-free supplement presented a similar morphology comparable to FBS-supplemented cells and maintained typical expression of markers: positive (&gt;95%) for CD90, CD73 and CD105; and negative (&lt;5%) for CD45, CD14, CD19, CD34 and HLA-DR. Likewise, hMSC showed potent, <em>in vitro</em> differentiation potential into osteogenic, chondrogenic and adipogenic lineages, outperforming the results obtained with traditional reference supplements in several instances. They retained their immunomodulatory properties, inhibiting the proliferation of phytohemagglutinin (PHA)-stimulated PBMCs with a notable enhancement of the immunomodulatory capacity of hMSCs compared to conventional reference supplements.</div></div><div><h3>Conclusions</h3><div>Plastem allowed hMSC expansion while preserving phenotype and showed remarkable differentiation and immunomodulatory properties, supporting its use for cell therapy manufacturing processes as a robust, xeno-free alternative to FBS and hPL. Moreover, Plastem can be manufactured at an industrial level, making it a scalable solution for widespread application.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 4","pages":"Pages 552-561"},"PeriodicalIF":3.7,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impacts of transient exposure of human T cells to low oxygen, temperature, pH and nutrient levels relevant to bioprocessing for cell therapy applications","authors":"Alina Kunitskaya ,&nbsp;James M. Piret","doi":"10.1016/j.jcyt.2025.01.002","DOIUrl":"10.1016/j.jcyt.2025.01.002","url":null,"abstract":"<div><h3>Background</h3><div>T-cell therapy advances have stimulated the development of bioprocesses to address the specialized needs of cell therapy manufacturing. During concentrated cell washing, the cells are frequently exposed to transiently reduced oxygen, temperature, pH, and nutrient levels. Longer durations of these conditions can be caused by process deviations or, if they are not harmful, be used to ease the scheduling of process stages during experiments as well as manufacturing.</div></div><div><h3>Methods</h3><div>To avoid unpredictable impacts on T-cell quality during bioprocessing, we measured the influences of such environmental exposures generated by settling 250 million activated human T cells per mL, for up to 6 h at temperatures from 4 to 37°C.</div></div><div><h3>Results</h3><div>The measured glucose concentration decreased to as low as 0.5 mM and the pH to 6, while lactate increased up to 55 mM. The concentrated cell conditions at 37°C resulted in by far the greatest losses in viable cell numbers with, on average, only 58% and 41% of the cells recovered after 3 and 6 h, respectively. Likewise, their subsequent cell expansion cultures were substantially reduced even after only 3 h of exposure, and with decreased percentages of central memory T cells and increased percentages of effector memory and effector T cells. Although under similar environmental conditions at room temperatures, the negative impacts of high cell concentrations were greatly diminished for up to 3 h. At 4°C the transient conditions were less extreme, and the cells well maintained for 6 h.</div></div><div><h3>Conclusions</h3><div>Overall, when developing processes and devices for T-cell therapy manufacturing that involve concentrated cells, the results of this study indicate that more practically feasible room temperatures can be used for up to 3 h to obtain high viable cell recoveries whereas lower temperatures such as 4°C should be used if there is a need for more prolonged concentrated T-cell conditions.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 4","pages":"Pages 522-533"},"PeriodicalIF":3.7,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CXCR5-targeted chimeric antigen receptor T regulatory cells for the selective inhibition of follicular helper T cell and B cell interaction.","authors":"Aiko Murai, Masashi Iwata, Shuuichi Miyakawa, Dnyaneshwar Warude, Masaki Sagara, Yusuke Kikukawa","doi":"10.1016/j.jcyt.2024.12.015","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.12.015","url":null,"abstract":"<p><strong>Background: </strong>The dysregulation of follicular helper T (Tfh) cell function, followed by the proliferation of self-reactive B cells, can lead to the development of autoimmune diseases. Recently, adaptive T regulatory cell (Treg) transfer therapy has attracted considerable attention for inducing effective immune tolerance owing to Tregs' diverse immune-inhibitory activities. However, preclinical studies and recent clinical trials of polyclonal Treg therapy have suggested further improving the efficacy of Treg therapy through targeted tissue specificity and local persistence by gene engineering. In this study, we reported a novel approach to specifically inhibit Tfh cells by CXC motif chemokine receptor 5-targeted chimeric antigen receptor (CXCR5-CAR) Tregs.</p><p><strong>Methods: </strong>Tregs expressing CAR against CXCR5 were generated from human peripheral blood mononuclear cells-derived Tregs. The phenotype and suppressive capacity of the engineered Tregs were evaluated using coculture assays with naïve T cells, circulating Tfh (cTfh) cells, or a combination of cTfh cells and naïve B cells through flow cytometry analysis.</p><p><strong>Result: </strong>CXCR5-CAR Tregs induced more potent inhibition of circulating cTfh cell proliferation while maintaining similar suppressive properties on CXCR5-negative responder cells compared with non-selective polyclonal Tregs. The antigen-dependent activation of CXCR5-CAR Tregs was confirmed by latency-associated peptide (LAP) expression in the coculture with cTfh cells. In the coculture condition with both cTfh and naïve B cells, the activation of naïve B cells induced by cTfh cells was more effectively inhibited by CXCR5-CAR Tregs than by polyclonal Tregs.</p><p><strong>Conclusion: </strong>The results demonstrate the potential of CXCR5-CAR Tregs to effectively inhibit the Tfh-B cell response in autoimmune diseases, paving the way for further research to confirm their functional superiority in vivo. This novel approach offers promise for achieving local, long-term immune tolerance compared with existing approaches such as nonspecific immunosuppression and polyclonal Treg therapy.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe hypophosphatemia following idecabtagene vicleucel regardless of the severity of cytokine release syndrome","authors":"Kenta Hayashino ,&nbsp;Wataru Kitamura ,&nbsp;Nobuharu Fujii ,&nbsp;Toshiki Terao ,&nbsp;Hiroki Kobayashi ,&nbsp;Chihiro Kamoi ,&nbsp;Takumi Kondo ,&nbsp;Keisuke Seike ,&nbsp;Hideaki Fujiwara ,&nbsp;Noboru Asada ,&nbsp;Daisuke Ennishi ,&nbsp;Keiko Fujii ,&nbsp;Yoshinobu Maeda","doi":"10.1016/j.jcyt.2024.12.014","DOIUrl":"10.1016/j.jcyt.2024.12.014","url":null,"abstract":"<div><h3>Background aims</h3><div>Hypophosphatemia has been recently recognized adverse event in chimeric antigen receptor (CAR)-T cell therapy, complicating 70–75% of patients. Severe hypophosphatemia can cause cytokine release syndrome (CRS)-like symptoms, such as respiratory and cardiovascular dysfunction. Some reports have described the association between inorganic phosphate (iP) and CRS in patients treated with tisagenlecleucel (tisa-cel), lisocabtagene maraleucel (liso-cel), axicabtagene ciloleucel (axi-cel). However, the association between iP and idecabtagene vicleucel (ide-cel) has not been reported and the kinetics of serum iP for each CAR-T cell product have not been compared. We aimed to analyze the kinetics of iP with CAR-T cell products, including ide-cel, and the association between hypophosphatemia and severe CRS.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed patients aged ≥ 18 years with B-cell malignancies who received CAR-T cell therapy in our institution. All available laboratory data were collected for 21 days after CAR-T cell infusion; clinical and laboratory data were extracted from electronic medical records.</div></div><div><h3>Results</h3><div>A total of 108 patients were treated with CAR-T cell therapy (tisa-cel, n = 56; liso-cel, n = 11; axi-cel, n = 28; ide-cel, n = 13). The cumulative incidence of hypophosphatemia and severe hypophosphatemia were significantly higher in the ide-cel group than the other CAR-T products group (92.3% versus 67.5%, <em>P</em> = 0.0045, and 15.4% versus 2.1%, <em>P</em> = 0.017), Patients treated with ide-cel had significantly lower serum iP levels from day −4 to 8 compared to other CAR-T products. As previous reports, the cumulative incidence of hypophosphatemia in the other CAR-T products group was significantly higher in the severe CRS group than in the mild CRS group (84.0% versus 60.0%, <em>P</em> = 0.0002). In contrast, there was no significant difference between the two groups in the ide-cel group (65% versus 100%, <em>P</em> = 0.13).</div></div><div><h3>Conclusion</h3><div>Our results suggest that and that it is important to monitor iP kinetics more carefully because patients treated with ide-cel complicate severe hypophosphatemia, regardless of CRS severity.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 4","pages":"Pages 516-521"},"PeriodicalIF":3.7,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dialysis and lyophilization of the mesenchymal stromal cell secretome for wound healing","authors":"Swapnali Sakhare ,&nbsp;Avinash Sanap ,&nbsp;Ramesh Bhonde ,&nbsp;Shubhanath Behera ,&nbsp;Pranjali Potdar ,&nbsp;Supriya Kheur ,&nbsp;Avinash Kharat","doi":"10.1016/j.jcyt.2024.12.013","DOIUrl":"10.1016/j.jcyt.2024.12.013","url":null,"abstract":"<div><h3>Background aims</h3><div>The clinical translation of mesenchymal stromal cell secretome (MSC-S) has been challenging owing to a lack of appropriate methods in downstream processing. Dialysis is an age-old method of protein purification by the exchange of small molecules through a semi-permeable membrane. In this study, we investigated the potential of three forms of umbilical cord–derived MSC secretome (UC-MSC-S)—native (S), dialyzed (DS), and lyophilized (LDS)—for wound healing applications.</div></div><div><h3>Methods and Results</h3><div>We dialyzed the UC-MSC-S using Slide-A-Lyzer G3 Dialysis Cassettes (20K MWCO) and then lyophilized it to obtain secretome powder. The DS fraction exhibited an 86.01-fold decrease compared with S, whereas LDS showed a 613.71-fold increase in the total protein concentration. Growth factor analysis revealed a significant decrease in the levels of interleukin-6 (IL-6; 54.44-fold), angiopoietin-1 (79.56-fold), angiopoietin-2 (51.76-fold), IL-8 (54.4-fold), platelet endothelial cell adhesion molecule-1 (PECAM-1; 63.25-fold), phosphatidylinositol glycan anchor biosynthesis class F (PIGF; 40.42-fold), vascular endothelial growth factor (VEGF; 39.64-fold), and tumor necrosis factor alpha (TNF-α; 24.62-fold) after dialysis as analyzed by the LEGEND plex multi-analyte flow assay kit on a FACS analyzer. Post-lyophilization, the levels of IL-6 (392.21-fold), angiopoietin-1 (823.04-fold), angiopoietin-2 (397.69-fold), IL-8 (584.83-fold), PECAM-1 (341.28-fold), PIGF (342.85-fold), VEGF (2209.42-fold), and TNF-α (194.4-fold) were enriched in LDS. The highest wound closure (64.07%) and a significant increase in angiogenesis were seen in DLS at the concentration of 1 µg/µL of protein by wound scratch and <em>in ovo</em> yolk sac membrane assay, respectively.</div></div><div><h3>Conclusions</h3><div>Dialysis followed by lyophilization is a simple and cost-effective method to fractionate and enrich the bioactive components of MSC-S without compromising the bioactivity for tailor-made applications.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 4","pages":"Pages 544-551"},"PeriodicalIF":3.7,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Higher risk of GVHD but better long-term survival: impact of p-ALG versus r-ATG in high-risk hematological malignancy patients following MSDT","authors":"Lingyan Yan MSc,&nbsp;Linli Lu MSc,&nbsp;Liwen Wang PhD,&nbsp;Yuhan Yan PhD,&nbsp;Yishu Tang MSc,&nbsp;Ying Li MD,&nbsp;Erhua Wang MD,&nbsp;Jian Zhang MD,&nbsp;Han Xiao MD,&nbsp;Qian Cheng MD ,&nbsp;Xin Li MD","doi":"10.1016/j.jcyt.2024.12.008","DOIUrl":"10.1016/j.jcyt.2024.12.008","url":null,"abstract":"<div><h3>Purpose</h3><div>Disease relapse and graft-versus-host disease (GVHD) represent significant clinical challenges for high-risk hematological malignancies (HM) patients undergoing HLA-matched sibling donor transplantation (MSDT). How to balance the effect of GVHD and Graft versus leukemia (GVL) remains unclear for high-risk HM patients receiving MSDT. Here, we conducted a retrospective study to compare the efficacy in preventing disease relapse of 2 lymphocyte-depleting antibodies (r-ATG vs p-ALG) as the GVHD prevention strategy.</div></div><div><h3>Method</h3><div>A retrospective analysis was conducted on 48 patients with high-risk HM patients who underwent MSDT at our center from January 2019 to January 2024. Among them, 22 patients were in the p-ALG group (45mg/kg), and 26 patients were in the r-ATG group (3.5–4.5mg/kg). The primary end point of this study was disease relapse.</div></div><div><h3>Results</h3><div>We found that the p-ALG group had a higher 3-year cumulative incidence of chronic GVHD than the r-ATG group (64.4% ± 13.6% vs. 28.8% ± 9.7%, <em>P</em> = 0.016). There was no significant difference in total acute GVHD (aGVHD) (54.5% ± 11% vs.26.9% ± 8.9%, <em>P = 0</em>.81) and 3-year extensive cGVHD (20.3% ± 11.3% vs. 7.9% ± 5.5%, <em>P = 0</em>.27) between the 2 groups. In terms of patient prognosis, the p-ALG group showed a higher 3-year overall survival rate compared to the r-ATG group (100% vs. 75.5% ± 8.8%, <em>P = 0</em>.039). The 3-year disease-free survival (DFS) rate was significantly higher in the p-ALG group compared to the r-ATG group (95.5% ± 4.4% versus 61% ± 10.6%, <em>P =</em> 0.046). Furthermore, the p-ALG group exhibited a longer duration of disease remission after transplantation, as evidenced by a lower 3-year cumulative incidence of post-transplantation Minimal Residual Disease positivity (post-MRD+) compared to the r-ATG group (4.5% ± 4.4% versus 40.5% ± 11%, <em>P =</em> 0.022).</div></div><div><h3>Conclusion</h3><div>In comparison to r-ATG, the administration of low-dose p-ALG (45mg/kg) in high-risk HM patients receiving MSDT is associated with an increased incidence of GVHD but results in a more favorable survival prognosis.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 4","pages":"Pages 500-507"},"PeriodicalIF":3.7,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}