MSCs play a major role in the preservation of both epithelial and endothelial barrier function in ARDS and sepsis.7 They can enhance alveolar fluid clearance and regulate epithelial and endothelial permeability through secretion of angiopoietin-1 and keratinocyte growth factor.8,9 A preclinical mouse model suggests that MSCs seem to attenuate sepsis via prostaglandin E2-dependent reprogramming of host macrophages to increase the level of interleukin (IL)-10.10 Importantly, MSCs are known to exert profound immunomodulatory effects on individual immune cell subset via soluble paracrine factors and direct cell-cell contact to modulate innate and acquired immune responses. Additionally, there are 42 other MSC-based clinical investigations worldwide registered on the NIH clinicaltrials.gov. Galipeau J, Sensébé L. Mesenchymal stromal cells: clinical challenges and therapeutic opportunities. In order to provide our website visitors and registered users with a service tailored to their individual preferences we use cookies to analyse visitor traffic and personalise content. Am J Respir Crit Care Med. 2009;4(3):206–216. All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work. The levels of IL-6, IL-23, and TGF-β remained constant after co-culture under either the Th17 or the Treg cell polarizing condition. 25. McIntyre LA, Stewart DJ, Mei SHJ, et al. ADSC) è una procedura molto più semplice e meno invasiva di estrazione del midollo osseo. Moreover, Ad-MSCs induced a functional CD4+CD25+Foxp3+T regulatory cell phenotype as evidenced by the secretion of IL-10. 2007;92(4):440–449. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. this site will not function whilst javascript is disabled. Zheng G, Huang L, Tong H, et al. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms. We offer real benefits to our authors, including fast-track processing of papers. We aimed to investigate the modulating effect of human Ad-MSCs on peripheral blood mononuclear cells (PBMCs) of patients with PD, focusing on differentiation into Th17 and Treg cells. We also retain data in relation to our visitors and registered users for internal purposes and for sharing information with our business partners. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. 2008;16(3):571–579. Utilizziamo il proprio tessuto adiposo del paziente quando vengono estratte le cellule staminali. Trattamento con cellule mesenchimali nelle patologie ortopediche a cura del Dott. This work is published and licensed by Dove Medical Press Limited. • software development by maffey.com 2020;395(10229):1054–1062. Matthay MA, Calfee CS, Zhuo H, et al. Spees JL, Lee RH, Gregory CA. Cheng Z, Ou L, Zhou X, et al. The route of administration is intravenous infusion of MSCs. Stem Cells Dev. Sci Rep. 2018;8(1):5251. Human adipose tissue-derived mesenchymal stem cells (Ad-MSCs) exert immunomodulatory effects by inhibiting effector T cell responses and have been used to treat diverse immune disorders. Cellule mesenchimali stromali: caratterizzazione immunofenotipica e funzionale. Effects of mesenchymal stem cell treatment on systemic cytokine levels in a phase 1 dose escalation safety trial of septic shock patients. We offer real benefits to our authors, including fast-track processing of papers. To date, rigorous results from clinical trials using MSCs in human have been weakly positive. 2020;323(11):1061–1069. Another phase I clinical trial registered on ClinicalTrials.gov (NCT01775774) was to test the safety of the dose-escalation allogeneic BM-MSCs in 9 patients with moderate to severe ARDS, using 1, 5, and 10×106 cells/kg, respectively.15 There were no MSC-related severe adverse events after infusions at any dosage. Le cellule staminali mesenchimali nel trattamento delle pseudoartrosi. doi:10.1016/S2213-2600(14)70217-6. PLoS One. Of special note, aging MSCs downregulate chemokine receptors, such as CCR7, CXC3CR1 and CXCR5, and MMP9,26 which may influence MSC homing capability. • software development by maffey.com 2019;196:18–30. Eur Respir J. Today the most frequently employed MSCs are derived from bone marrow. Cellule Staminali Mesenchimali. Nei casi in cui le terapie conservative (mediche e fisioterapiche) siano inefficaci, è possibile ricorrere alla medicina rigenerativa e sottoporsi quindi ad infiltrazioni intrarticolari o nei tessuti cutanei lesi, che, come detto precedentemente, contengono cellule mesenchimali. Han J, Liu Y, Liu H, Li Y. Several features of Le cellule staminali mesenchimali (MSC), ottenute dal midollo osseo adulto, possono rappresentare una fonte cellulare per la rigenerazione ossea . Sono delle cellule staminali adulte multipotenti in grado di replicarsi e trasformarsi in altri tipi di cellula. Khoury M, Cuenca J, Cruz FF, Figueroa FE, Rocco PRM, Weiss DJ. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Maurizio Magnani. Only a small number of the infused MSCs after administration are distributed to other tissues. Isolamento e resa - Come? 2012;30:1565–1574. • Top, © Copyright 2020 • Dove Press Ltd 2020;11(1):169. doi:10.1186/s13287-020-01678-8, 6. Il metodo di prelievo di cellule dal grasso è simile alla liposuzione. Stem Cell Res Ther. Copyright 2017 Informa PLC. 10. Sci Rep. 2015;5:13744. open access to scientific and medical research. Queste cellule hanno una forte azione antinfiammatoria, antidegenerativa e stimolano la produzione di cartilagine. Personalmente dal 2014 sto utilizzando la tecnica delle cellule staminali mesenchimali prelevate dal • Recommend this site Appunti - Biotecnologie cellulari - Cellule staminali mesenchimali - a.a. 2015/2016. Although genetic engineering strategies can improve therapeutic potential of MSCs, safety issues remain under debate, such as MSC transformation, trans-differentiation and confliction of MSC innate properties. In addition, levels of LIF protein and its receptor mRNA were significantly increased under both polarizing conditions.Conclusion: The present in vitro study found that Ad-MSCs from healthy participants were able to correct the imbalance between Th17 and Treg found in PBMCs of PD patients, which were correlated with an increase in LIF secretion and a decrease in expression of IL-6R, IL-23R, and RORγt. 32. More Citation Formats Moll D, Rasmusson-Duprez I, von Bahr L, et al. 2. Bulk reprints for the pharmaceutical industry. You can learn about our use of cookies by reading our Privacy Policy. Based on this phase I experience, the same team conducted a subsequent double-blind, multicentre and randomized phase IIa clinical study to further assess treatment with one intravenous dose of BM-MSCs at the high dose (10×106 cells/kg) in 40 patients with moderate to severe ARDS.16 This phase IIa clinical trial showed that no MSC infusion-related haemodynamic or respiratory adverse events were identified, but the MSCs group had higher disease severity scores than the placebo group at baseline. Cell Stem Cell. Creative Commons Attribution - Non Commercial (unported, v3.0) License. In conclusion, MSCs are currently being explored as a new treatment option for COVID-19. Several features of doi:10.1016/j.stem.2009.02.001. All rights reserved. Dr Yan Zhu, Chenghai Li,1,2,* Hua Zhao,3,4,* Bin Wang5 1Stem Cell Program of Clinical Research Center, Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Zhengzhou 450003, People’s Republic of China; 2Henan Key Laboratory of Stem Cell Differentiation and Modification, Zhengzhou 450003, People’s Republic of China; 3Reproductive Medicine Institute, Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Zhengzhou 450003, People’s Republic of China; 4People’s Hospital of Henan University, Zhengzhou 450003, People’s Republic of China; 5Department of Neurosurgery, Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Zhengzhou 450003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin Wang; Chenghai Li Email bin.wang201166@hotmail.com; chenghai_li@yahoo.comAbstract: The coronavirus disease 2019 (COVID-19) global pandemic continues and antiviral agents and vaccines are currently under investigation. Guo Z, Chen Y, Luo X, He X, Zhang Y, Wang J. We detected levels of cytokines in the supernatant (including LIF, IL-6, IL-23, IL-10, and TGF-β) using ELISA.Results: Our results showed that Ad-MSCs specifically inhibited the differentiation of PBMCs of patients with PD into IL-17-producing CD4+T cells by decreasing expressions of IL-6R, IL-23R, and RORγt (the key transcription factor for Th17 cells). Open access peer-reviewed scientific and medical journals. The above percentage of manuscripts have been rejected in the last 12 months. Transplantation of ACE2− mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia. Cellular immunotherapy for septic shock (CISS): a phase I clinical trial. Human MSCs have drawn increasing attention for stem cell-based therapy in translational medicine. While many pre-clinical studies propose that MSCs have immunomodulatory properties, rigorous results from clinical trials have been less positive.6 So far, there are limited clinical data available, but an increasing number of clinical trials are still underway using MSCs for the treatment of COVID-19. Therefore, to avoid thrombotic risk, a lower dose of MSCs harvested in low passage may prove to be a more suitable candidate as a treatment option. MSC-derived exosomes can significantly increase the migration of MSCs in a time- and dose-dependent manner.30 Importantly, the release of exosomes from MSCs is increased through a hypoxia-induced paracrine mechanism.30 One recent clinical study suggests that MSC-exosome administration is a therapeutic candidate for severe COVID-19.13 However, MSC-exosome stability, storage, motility, distribution and response in vivo need further optimization. Da oltre 50 anni Humanitas San Pio X è un punto di riferimento per pazienti e medici, riconosciuta fin dalle sua origine per la vocazione al servizio, alla cura e all’assistenza dei malati. The timing of MSC administration is critical, as life-threatening injury (eg, cytokine storm syndrome) to organs often develops quickly. le cellule staminli mesenchimali cellule staminali possono essere anche le cellule mesenchimali, le quali vengono isolate da tessuti adulti, fatte espandere in. UK VAT Group: GB 365 4626 36. Abraham A, Krasnodembskaya A. Mesenchymal stem cell-derived extracellular vesicles for the treatment of acute respiratory distress syndrome. Lancet. 2018;199:52–61. The underlying mechanisms by which MSCs exert a therapeutic influence include anti-inflammation, immunomodulation and tissue remodeling (Figure 1). Inoltre, il tessuto adiposo contiene più cellule staminali mesenchimali … Le cellule staminali sono cellule primitive non specializzate. Wilson JG, Liu KD, Zhuo H, Caballero L, McMillan M, Fang X. Mesenchymal stem (stromal) cells for treatment of ARDS: a Phase 1 clinical trial. Ecco perché queste cellule potrebbero rappresentare una importante novità nel trattamento dei danni cartilaginei. Wang D, Hu B, Hu C, et al. Per ottenere cellule sufficiente per essere utili , queste cellule vengono estratte e coltivate in laboratorio dove possono moltiplicarsi. However, several immediate and urgent challenges have to be addressed for the development of the more safe and effective MSC-based approaches for COVID-19. Concise review: mesenchymal stem cells for acute lung injury: role of paracrine soluble factors. 2020;9:28–38. Self renewal and differentiation Stem cell Progenitor cell Differentiated cell Symmetric stem cell divison ... Mesenchymal progenitor cell Few Cartilage cells, myocyte, bone-forming cells, fat cells, endothelial cells, neural cells. Registered in England and Wales. Contact Us Haematologica. You can learn about what data of yours we retain, how it is processed, who it is shared with and your right to have your data deleted by reading our Privacy Policy. 2011;29(6):913–919. Human adipose tissue-derived mesenchymal stem cells (Ad-MSCs) exert immunomodulatory effects by inhibiting effector T cell responses and have been used to treat diverse immune disorders. 18. Here, we present a protocol for the dissection of human umbilical cord (UC) and fetal placenta sample into cord lining (CL), Wharton's jelly (WJ), cord-placenta junction (CPJ), and fetal placenta (FP) for the isolation and characterization of mesenchymal stromal cells (MSCs) using the explant culture technique. Lo Scalpello - Journal . This work was supported by Henan Key Laboratory of Stem Cell Differentiation and Modification. To help accelerate the development of MSC products as therapeutic options, a few stem cell biotechs are joining forces, such as Mesoblast, Athersys, Hope Biosciences and Aspire Health Science. Mesenchymal stem cell (MSC)-based therapy can be a suitable option for management of patients with COVID-19 at the urgent time of virus outbreak. Daverey A, Drain AP, Kidambi S. Physical intimacy of breast cancer cells with mesenchymal stem cells elicits Trastuzumab resistance through Src activation. Mechanisms of mesenchymal stem/stromal cell function. If you agree to our use of cookies and the contents of our Privacy Policy please click 'accept'. The opinions expressed in all articles published here are those of the specific author(s), and do not necessarily reflect the views of Dove Medical Press Ltd or any of its employees. 2020;11(2):216–228. Schlosser K, Wang JP, Dos Santos C, et al. Le cellule mesenchimali sono cellule staminali adulte e indifferenziate che possono mutare in cellule di vari tessuti come cellule del tessuto osseo, adiposo, cartilagineo, cardiaco e muscolare… First, a key issue is the fate of MSCs after intravenous injection. The urgency should also be met with a concurrent exploration of other effective biological treatments against COVID-19. Current status of cell-based therapies for respiratory virus infections: applicability to COVID-19. Le cellule mesenchimali (oMSC1) possono essere definite in termini semplici come delle unità biologiche di base “tuttofare”, estremamente versatili e capaci di dar vita a molti tipi diversi di tessuto. Il corpo umano contiene centinaia di tipi cellulari divesi, che sono di primaria importanza per la nostra salute quotidiana. Compared with the control cohort, patients treated with MSCs showed significant improvement of clinical outcomes and there were no reports of MSC infusion-associated adverse events. Cellule staminali mesenchimali per la cartilagine del ginocchio: la mia esperienza. Dalle cellule mesenchimali (mesoderma) derivano i tessuti connettivi, quindi NON le cellule epiteliali. Queste cellule hanno un’azione anti-apoptotica, immunomodulatoria e mitogenica, producono fattori di crescita che stimolano la rigenerazione cellulare di quel determinato microambiente in cui risiedono od in cui vengono inserite. For example, CXCR4 transgene expression in genetically modified MSCs enhances MSC homing toward the infarct region of the myocardium and improves cardiac performance in a rat myocardial infarction model.32 One pre-clinical study has reported the modified MSCs to overcome the detrimental lung microenvironment in acute lung injury.21 In that study, treatment with modified MSCs carrying either human hepatocyte growth factor or IL-10 resulted in impressive reductions in lung injury state, fibrosis and inflammation. Are therapeutic human mesenchymal stromal cells compatible with human blood? Several immediate and urgent challenges have to be addressed for the development of the MSC-based approaches for COVID-19. He X, Ai S, Guo W, et al. Italian Cosa sono le cellule staminali? From submission to first editorial decision. 23. doi:10.1089/scd.2020.0080, 14. Number 3099067. Second, whether the circulating MSCs will be cleared from the body after systemic infusion by the humoral components (eg, complements) and immune cell subsets (eg, macrophages) of the immune system should be carefully considered. Stem Cell Res Ther. Interestingly, there is a nonrandomized open-label cohort study using exosomes secreted from bone marrow-derived MSCs (BM-MSCs) as treatment for severe COVID-19.13 Sengupta et al conducted this study that presented the clinical and laboratory data following a single intravenous dose of exosomes derived from BM-MSCs to address a promising therapeutic candidate for severe COVID-19.13 Aforementioned, these pilot clinical studies indicate beneficial effects of MSCs and MSC-derived exosomes in COVID-19, but the safety and consistent efficacy need validation from large studies. High culture confluence has been shown to inhibit transendothelial migration of expanded MSCs by an upregulation of MMP-inhibitor TIMP3.27 MSCs might lose certain surface receptors during serial MSC passaging, which may also affect MSC homing ability. Mesoblast has made decision to evaluate the therapeutic effects of an allogeneic MSC product candidate (Remestemcel-L) in COVID-19 patients with ARDS (http://www.mesoblast.com/). MSC-mediated compound/drug resistance frequently occurs in MSC-based anti-cancer therapy,22,23 resulting from tumor microenvironment protecting cancer cells against treatment. Registered in England and Wales. 33, 3 (Dec. 2019), 270 - 274. Humanitas San Pio X a Milano offre prestazioni di assistenza in regime di ricovero ordinario, day Hospital e day surgery. Zhou F, Yu T, Du R, et al. Lancet Respir Med. If you agree to our use of cookies and the contents of our Privacy Policy please click 'accept'. This site is owned and operated by Informa PLC ( “Informa”) whose registered office is 5 Howick Place, London SW1P 1WG. 2019;7(2):154–162. Mesenchymal stem cell (MSC)-based therapy can be a suitable option for management of patients with COVID-19 at the urgent time of virus outbreak. Le MSC vengono isolate dal midollo osseo mediante un prelievo percutaneo [7] e vengono fatte differenziare verso la linea osteogenica se coltivate in presenza di desametasone, acido ascorbico e β-glicerolfosfato (mezzo osteogenico) [8] . Athersys, another stem cell biotechnology company in Cleveland, Ohio, has been developing a possible therapy for ARDS caused by COVID-19 (https://www.athersys.com/news-and-media/default.aspx). 2020;29(12):747–754. Dove Medical Press is part of Taylor & Francis Group, the Academic Publishing Division of Informa PLC Sono capaci di auto-rigenerarsi e di differenziarsi in diversi tipi di cellule con funzioni specifiche. Higher cell doses and higher passage numbers of MSCs promote their prothrombotic profile. doi:10.1002/stem.1111, 21. Le cellule mesenchimali sono delle cellule staminali adulte multipotenti in grado di replicarsi e trasformarsi in altri tipi … Hanno proprietà immunomodulatorie, ovvero sono in grado di regolare le alterazioni delle risposte del sistema immunitario, hannocapacità an… Aerosol inhalation of MSC-derived exosomes (ChiCTR2000030261 and NCT04276987) may be an apt route of administration to avoid the impact of virus on MSCs. Back to Journals » Drug Design, Development and Therapy » Volume 14, Challenges for Mesenchymal Stem Cell-Based Therapy for COVID-19, Accepted for publication 6 September 2020, Published 29 September 2020 It should be appreciated that the lung microenvironment can profoundly influence the properties of MSCs and their beneficial effects on ARDS upon initiating MSC administration.21 Previous study by Islam et al showed that stimulation of human MSCs with plasma of ARDS patients resulted in the decrease of CD105 and CD90 for 5 days, suggesting a phenotype shift.21 This observation also suggests the need to consider whether ACE2 on MSC surface may be altered by the inflammatory environment. Il Sangue del Cordone Ombelicale: alcune considerazioni in chiave Medico-Legale. In addition, there are two phase I clinical trials of MSCs in patients with severe sepsis and septic shock.17,18 He et al conducted a phase I clinical trial using UC-MSCs for treatment of severe sepsis.17 A single intravenous infusion of UC-MSCs of low (1×106 cells/kg), intermediate (2×106 cells/kg), and high (3×106 cells/kg) dosage cohorts were confirmed safe and well tolerated in 15 participants with severe sepsis, respectively.17 Another similar phase I dose-escalation trial of BM-MSCs in septic shock (NCT02421484) conducted by Mclntyre et al showed no adverse safety signals in the three BM-MSC dose cohorts of three participants each receiving a single dose of 0.3, 1.0 and 3.0×106 cells/kg, respectively.18 The same team proceeded to a subsequent phase I clinical study in septic shock patients receiving the same dose-escalation BM-MSC infusion to investigate the safety and biological effects of BM-MSC treatment.19 No significant increase in pro-inflammatory cytokines was detected in plasma samples from septic shock patients within the 72-hour time course after BM-MSC infusion, suggesting that MSC treatment may alter underlying sepsis biology. Research on homing capability of MSCs in vitro is inconclusive, because in vitro assays do not mimic the cells’ journey in vivo.
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