PMC:7019005 / 2101-4050 JSONTXT

{"project":"TEST0","denotations":[{"id":"32117276-190-195-3576133","span":{"begin":682,"end":683},"obj":"[\"29098010\"]"},{"id":"32117276-236-241-3576134","span":{"begin":953,"end":954},"obj":"[\"29098010\", \"27870924\", \"27888550\"]"},{"id":"32117276-81-86-3576135","span":{"begin":1755,"end":1756},"obj":"[\"30106875\"]"}],"text":"The lack of effective therapy for sepsis remains a major unmet medical need. Even though substantial progress has been made in understanding the underlying pathophysiology of sepsis, translation of these advances into clinically effective therapies has been disappointing. Given the extreme complexity of sepsis pathogenesis, the paradigm “one disease, one drug” is obviously flawed and combinations of multiple targets that involve early immunomodulation and cellular protection are needed. The immunomodulatory, anti-inflammatory, anti-apoptotic, metabolomic, and anti-microbial effects of mesenchymal stem cells (MSCs) may have scientific and clinical relevance in this context (1). Indeed, application of MSCs in preclinical models of sepsis has been associated with lower mortality, improved course of sepsis due to inhibition of pro-active elements of the immune system, and a change in the pro- and anti-cytokine ratio both in vitro and in vivo (1–3). In addition, no preclinical study published so far has demonstrated adverse effects associated with the application of MSCs in animal models of sepsis. It must be emphasized, however, that these encouraging results were largely derived from rodent models with clearly limited relevance to human sepsis. Hence, a thorough investigation of the effects of MSCs in clinically relevant large-animal models is urgently needed before translation to the clinical field. Therefore, we conducted a randomized controlled experimental study to explore the biological effects of MSCs on the background of standard care in comparison to standard conservative therapy in a porcine model of peritonitis-induced progressive sepsis. The model fulfills recently defined requirements for preclinical sepsis studies (4). We aimed to examine both the safety of MSCs in healthy animals and the effect of MSCs on various biological systems related to multiple pathophysiological pathways during sepsis progression."}

{"project":"2_test","denotations":[{"id":"32117276-29098010-35127740","span":{"begin":682,"end":683},"obj":"29098010"},{"id":"32117276-29098010-35127741","span":{"begin":953,"end":954},"obj":"29098010"},{"id":"32117276-27870924-35127741","span":{"begin":953,"end":954},"obj":"27870924"},{"id":"32117276-27888550-35127741","span":{"begin":953,"end":954},"obj":"27888550"},{"id":"32117276-30106875-35127742","span":{"begin":1755,"end":1756},"obj":"30106875"}],"text":"The lack of effective therapy for sepsis remains a major unmet medical need. Even though substantial progress has been made in understanding the underlying pathophysiology of sepsis, translation of these advances into clinically effective therapies has been disappointing. Given the extreme complexity of sepsis pathogenesis, the paradigm “one disease, one drug” is obviously flawed and combinations of multiple targets that involve early immunomodulation and cellular protection are needed. The immunomodulatory, anti-inflammatory, anti-apoptotic, metabolomic, and anti-microbial effects of mesenchymal stem cells (MSCs) may have scientific and clinical relevance in this context (1). Indeed, application of MSCs in preclinical models of sepsis has been associated with lower mortality, improved course of sepsis due to inhibition of pro-active elements of the immune system, and a change in the pro- and anti-cytokine ratio both in vitro and in vivo (1–3). In addition, no preclinical study published so far has demonstrated adverse effects associated with the application of MSCs in animal models of sepsis. It must be emphasized, however, that these encouraging results were largely derived from rodent models with clearly limited relevance to human sepsis. Hence, a thorough investigation of the effects of MSCs in clinically relevant large-animal models is urgently needed before translation to the clinical field. Therefore, we conducted a randomized controlled experimental study to explore the biological effects of MSCs on the background of standard care in comparison to standard conservative therapy in a porcine model of peritonitis-induced progressive sepsis. The model fulfills recently defined requirements for preclinical sepsis studies (4). We aimed to examine both the safety of MSCs in healthy animals and the effect of MSCs on various biological systems related to multiple pathophysiological pathways during sepsis progression."}

{"project":"MyTest","denotations":[{"id":"32117276-29098010-35127740","span":{"begin":682,"end":683},"obj":"29098010"},{"id":"32117276-29098010-35127741","span":{"begin":953,"end":954},"obj":"29098010"},{"id":"32117276-27870924-35127741","span":{"begin":953,"end":954},"obj":"27870924"},{"id":"32117276-27888550-35127741","span":{"begin":953,"end":954},"obj":"27888550"},{"id":"32117276-30106875-35127742","span":{"begin":1755,"end":1756},"obj":"30106875"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"The lack of effective therapy for sepsis remains a major unmet medical need. Even though substantial progress has been made in understanding the underlying pathophysiology of sepsis, translation of these advances into clinically effective therapies has been disappointing. Given the extreme complexity of sepsis pathogenesis, the paradigm “one disease, one drug” is obviously flawed and combinations of multiple targets that involve early immunomodulation and cellular protection are needed. The immunomodulatory, anti-inflammatory, anti-apoptotic, metabolomic, and anti-microbial effects of mesenchymal stem cells (MSCs) may have scientific and clinical relevance in this context (1). Indeed, application of MSCs in preclinical models of sepsis has been associated with lower mortality, improved course of sepsis due to inhibition of pro-active elements of the immune system, and a change in the pro- and anti-cytokine ratio both in vitro and in vivo (1–3). In addition, no preclinical study published so far has demonstrated adverse effects associated with the application of MSCs in animal models of sepsis. It must be emphasized, however, that these encouraging results were largely derived from rodent models with clearly limited relevance to human sepsis. Hence, a thorough investigation of the effects of MSCs in clinically relevant large-animal models is urgently needed before translation to the clinical field. Therefore, we conducted a randomized controlled experimental study to explore the biological effects of MSCs on the background of standard care in comparison to standard conservative therapy in a porcine model of peritonitis-induced progressive sepsis. The model fulfills recently defined requirements for preclinical sepsis studies (4). We aimed to examine both the safety of MSCs in healthy animals and the effect of MSCs on various biological systems related to multiple pathophysiological pathways during sepsis progression."}