Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial

Matthay, Michael A.; Calfee, Carolyn S.; Zhuo, Hanjing; Thompson, B. Taylor; Wilson, Jennifer G.; Levitt, Joseph E.; Rogers, Angela; Gotts, Jeffrey E.; Wiener-Kronish, Jeanine P.; Bajwa, Ednan K.; Donahoe, Michael P.; McVerry, Bryan J.; Ortiz, Luis A.; Exline, Matthew C.; Christman, John W.; Abbott, Jason; Delucchi, Kevin; Caballero, Lizette; McMillan, Melanie; McKenna, David H.; Liu, Kathleen D.

doi:10.1016/s2213-2600(18)30418-1

Cited by 491 publications

(551 citation statements)

References 32 publications

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“…Ahn and the colleagues had demonstrated that intratracheal transplantation of allogeneic hUCB‐derived mesenchymal stem cells (MSCs) is safe, feasible, and effective in preterm infants at high risk for BPD . Matthay and team showed that IV allogeneic BM‐MSCs was safe in adults with ARDS . Compared with other stem cell types in cord blood, MSCs are more attractive to researchers, as it is non‐immunogenic and can be expanded rapidly ex vivo .…”

Section: Discussionmentioning

confidence: 99%

“…Compared with other stem cell types in cord blood, MSCs are more attractive to researchers, as it is non‐immunogenic and can be expanded rapidly ex vivo . With these properties, allogeneic transplantation of MSCs are used for treatment of diseases in adult and neonates . ACBMNC, as a convenient source of MSC, has never been studied in prevention or treatment of BPD in preterm.…”

Section: Discussionmentioning

confidence: 99%

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Autologous cord blood cell infusion in preterm neonates safely reduces respiratory support duration and potentially preterm complications

Ren

Zhang

et al. 2019

Stem Cells Translational Medicine

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Preterm birth and its complications are the leading cause of neonatal death. The main underlying pathological mechanisms for preterm complications are disruption of the normal maturation processes within the target tissues, interrupted by premature birth.Cord blood, as a new and convenient source of stem cells, may provide new, promising options for preventing preterm complications. This prospective, nonrandomized placebo controlled study aimed at investigating the effect of autologous cord blood mononuclear cells (ACBMNC) for preventing preterm associated complications. Preterm infants less than 35 weeks gestational age were assigned to receive ACBMNC (5 × 10 7 cells/kg) intravenous or normal saline within 8 hours after birth. Preterm complication rates were compared between two groups to demonstrate the effect of ACBMNC infusion in reducing preterm complications. Fifteen preterm infants received ACBMNC infusion, and 16 infants were assigned to the control group. There were no significant differences when comparing mortality and preterm complication rates before discharge. However, ACBMNC infusion demonstrated significant decreases in duration of mechanical ventilation (3.2 days vs 6.41 days, P = .028) and oxygen therapy (5.33 days vs 11.31 days, P = .047). ACBMNC infusion was effective in reducing respiratory support duration in very preterm infants. Due to the limited number of patients enrolled, powered randomized controlled trials are needed to better define its efficacy. K E Y W O R D Sautologous cord blood cells, effect, preterm complication, prevention

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Autologous cord blood cell infusion in preterm neonates safely reduces respiratory support duration and potentially preterm complications

Ren

Zhang

et al. 2019

Stem Cells Translational Medicine

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“…Importantly, data from a Phase2a trial in ARDS due to other etiologies reported no significant infusional toxicities or other safety issues other than the death of one patient 24h after MSC infusion, which was judged to be unrelated to cell administration. [6] With respect to clinical efficacy results to date are ambiguous. For example, the Phase2a ARDS START trial reported a trend toward higher mortality in the MSC vs. placebo arm that was attributed to patient randomization, [6] and results from a Phase1/2 trial of MSC administration in ARDS sponsored by Athersys is awaiting publication.…”

Section: Resultsmentioning

confidence: 99%

“…[6] With respect to clinical efficacy results to date are ambiguous. For example, the Phase2a ARDS START trial reported a trend toward higher mortality in the MSC vs. placebo arm that was attributed to patient randomization, [6] and results from a Phase1/2 trial of MSC administration in ARDS sponsored by Athersys is awaiting publication. One significant unresolved issue in this respect is which COVID-19 patient population to target.…”

Section: Resultsmentioning

confidence: 99%

“…This is consistent with the general experience with single IV administration of MSCs in a range of clinical settings, including a Phase2a clinical study in ARDS. [6] All patients, including the one categorized as critically severe, demonstrated clinical improvements within 2-4 days after MSC administration, including resolution of clinical symptoms (fever, cough, elevated respiratory rates) and improvements in oxygen saturation. However, while detailed information is provided for the critically severe patient, there is a lack of corresponding information for the other six patients.…”

Section: Clinical Investigations Of Msc Administration In Patients Wimentioning

confidence: 93%

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Cell-based therapies for coronavirus disease 2019: proper clinical investigations are essential

et al. 2020

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The serious consequences of the global COVID-19 pandemic have prompted a rapid gobal response to develop effective therapies that can lessen disease severity in infected patients.Cell-based approaches, primarily using mesenchymal stromal cells (MSCs), have demonstrated a strong safety profile and possible efficacy in patients with the acute respiratory distress syndrome (ARDS), but whether these therapies are effective for treating respiratory virus-induced ARDS is unknown. According to the WHO ICTRP and the NIH clinicaltrials.gov databases, 27 clinical investigations of MSC-based cell therapy approaches have begun in China since the onset of the COVID-19 outbreak, as well as a growing number of academic and industry trials elsewhere. Several recent published reports have suggested potential efficacy; however, the available data presented is either anecdotal or from incomplete, poorly controlled investigations. Therefore, while there may be a potential role for MSCs and other cell-based therapies in treatment of COVID-19, these need to be investigated in a rationally designed, controlled approach if safety and efficacy are to be demonstrated accurately. We urge that the field proceeds by finding balance between swift experimentation and communication of results, and scientifically coherent generation and analysis of clinical data.

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Pharmacological agents for adults with acute respiratory distress syndrome

Lewis

Pritchard

Thomas

et al. 2019

Cochrane Database of Systematic Reviews

140

136

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Background Acute respiratory distress syndrome (ARDS) is a life-threatening condition caused by direct or indirect injury to the lungs. Despite improvements in clinical management (for example, lung protection strategies), mortality in this patient group is at approximately 40%. This is an update of a previous version of this review, last published in 2004. Objectives To evaluate the e ectiveness of pharmacological agents in adults with ARDS on mortality, mechanical ventilation, and fitness to return to work at 12 months. Search methods We searched CENTRAL, MEDLINE, Embase, and CINAHL on 10 December 2018. We searched clinical trials registers and grey literature, and handsearched reference lists of included studies and related reviews. Selection criteria We included randomized controlled trials (RCTs) comparing pharmacological agents with control (placebo or standard therapy) to treat adults with established ARDS. We excluded trials of nitric oxide, inhaled prostacyclins, partial liquid ventilation, neuromuscular blocking agents, fluid and nutritional interventions and medical oxygen. We excluded studies published earlier than 2000, because of changes to lung protection strategies for people with ARDS since this date. Data collection and analysis Two review authors independently assessed studies for inclusion, extracted data, and assessed risks of bias. We assessed the certainty of evidence with GRADE. Main results We included 48 RCTs with 6299 participants who had ARDS; two included only participants with mild ARDS (also called acute lung injury). Most studies included causes of ARDS that were both direct and indirect injuries. We noted di erences between studies, for example the time of administration or the size of dose, and because of unclear reporting we were uncertain whether all studies had used equivalent lung protection strategies.

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Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial

Cited by 491 publications

References 32 publications

Autologous cord blood cell infusion in preterm neonates safely reduces respiratory support duration and potentially preterm complications

Autologous cord blood cell infusion in preterm neonates safely reduces respiratory support duration and potentially preterm complications

Cell-based therapies for coronavirus disease 2019: proper clinical investigations are essential

Pharmacological agents for adults with acute respiratory distress syndrome

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