Mesenchymal stem cells and infectious diseases: Smarter than drugs

Mezey, Éva; Nemeth, Michael J.

doi:10.1016/j.imlet.2015.05.020

Cited by 77 publications

(61 citation statements)

References 90 publications

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“…7,8 Animal studies have demonstrated the effect of cord blood stem cells infusion in prevention and treatment of preterm-related complications such as bronchopulmonary dysplasia (BPD), sepsis, and hypoxic ischemic encephalopathy (HIE). 9,10 Evidence from several clinical trials proved the safety and feasibility of autologous cord blood infusion in neonates. 4,[11][12][13][14][15] However, there are very limited data about preterm neonates.…”

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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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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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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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“…This patient had clinically inactive disease overall. It seems that macrophage-derived pro-inflammatory signals are necessary for the MSCs to exert their effect efficiently [37].…”

Section: Discussionmentioning

confidence: 99%

Bone Marrow-Derived Mesenchymal Stromal Cells (MSCs) Modulate the Inflammatory Character of Alveolar Macrophages from Sarcoidosis Patients

Caldwell

Hogden

Németh

et al. 2020

JCM

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Sarcoidosis is a devastating inflammatory disease affecting many organs, especially the lungs and lymph nodes. Bone marrow-derived mesenchymal stromal cells (MSCs) can “reprogram” various types of macrophages towards an anti-inflammatory phenotype. We wanted to determine whether alveolar macrophages from sarcoidosis subjects behave similarly by mounting an anti-inflammatory response when co-cultured with MSCs. Fifteen sarcoidosis and eight control subjects underwent bronchoscopy and bronchoalveolar lavage (BAL). Unselected BAL cells (70–94% macrophages) were isolated and cultured with and without MSCs from healthy adults. Following stimulation of the cultured cells with lipopolysaccharide, the medium was removed to measure interleukin 10 and tumor necrosis factor alpha (IL-10 and TNF-α). In two additional sarcoidosis subjects, flow cytometry was used to study intracellular cytokines and surface markers associated with alveolar macrophages to confirm the results. Unselected BAL cells from sarcoidosis subjects co-cultured with MSCs showed a reduction in TNF-α (pro-inflammatory M1) and an increase in IL-10 (anti-inflammatory M2) in 9 of 11 samples studied. Control subject samples showed few, if any, differences in cytokine production. Unselected BAL cells from two additional patients analyzed by flow cytometry confirmed a switch towards an anti-inflammatory state (i.e., M1 to M2) after co-culture with MSCs. These results suggest that, similarly to other macrophages, alveolar macrophages also respond to MSC contacts by changing towards an anti-inflammatory phenotype. Based on our results, we hypothesize that mesenchymal stromal cells applied to the airways might alleviate lung inflammation and decrease steroid need in patients with sarcoidosis.

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“…Although it is capable of self-renewal, it also has the potential to differentiate into various cellular phenotypes. In addition, its paracrine effect contributes to tissue repair and immune modulation (7,11,12). Animal studies have demonstrated the beneficial effects of the infusion of cord blood stem cells in the prevention and treatment of lung injury, including experimental BPD (13)(14)(15).…”

Section: Clinical Trial Registrationmentioning

confidence: 99%

Use of Autologous Cord Blood Mononuclear Cells Infusion for the Prevention of Bronchopulmonary Dysplasia in Extremely Preterm Neonates: A Study Protocol for a Placebo-Controlled Randomized Multicenter Trial [NCT04440670]

Ren

Zhang

et al. 2020

Front. Pediatr.

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Background: Despite the rapid advance of neonatal care, bronchopulmonary dysplasia (BPD) remains a significant burden for the preterm population, and there is a lack of effective intervention. Stem cell depletion because of preterm birth is regarded as one of the underlying pathological mechanisms for the arrest of alveolar and vascular development. Preclinical and small-sample clinical studies have proven the efficacy and safety of stem cells in treating and preventing lung injury. However, there are currently no randomized clinical trials (RCTs) investigating the use of autologous cord blood mononuclear cells (ACBMNC) for the prevention of BPD in premature infants. The purpose of this study is to investigate the effects of infusion of ACBMNC for the prevention of BPD in preterm neonates <28 weeks.Methods: In this prospective, randomized controlled double-blind multi-center clinical trial, 200 preterm neonates <28 weeks gestation will be randomly assigned to receive intravenous ACBMNC infusion (5 × 10 7 cells/kg) or placebo (normal saline) within 24 h after birth in a 1:1 ratio using a central randomization system. The primary outcome will be survival without BPD at 36 weeks of postmenstrual age or at discharge, whichever comes Ren et al.Cord Blood Cells for Bronchopulmonary Dysplasia Prevention first. The secondary outcomes will include the mortality rate, other common preterm complication rates, respiratory support duration, length, and cost of hospitalization, and long-term outcomes after a 2-year follow-up.Conclusion: This will be the first randomized, controlled, blinded trial to evaluate the efficacy of ACBMNC infusion as a prevention therapy for BPD. The results of this trial will provide valuable clinical evidence for recommendations on the management of BPD in extremely preterm infants. Clinical Trial Registration:ClinicalTrials.gov, NCT03053076, registered 02/14/2017, retrospectively registered, https://register.clinicaltrials.gov/prs/app/ action/SelectProtocol?sid=S0006WN4&selectaction=Edit&uid=U0002PLA&ts=2&cx= 9y23d4 (Additional File 2).

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Mesenchymal stem cells and infectious diseases: Smarter than drugs

Cited by 77 publications

References 90 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

Bone Marrow-Derived Mesenchymal Stromal Cells (MSCs) Modulate the Inflammatory Character of Alveolar Macrophages from Sarcoidosis Patients

Use of Autologous Cord Blood Mononuclear Cells Infusion for the Prevention of Bronchopulmonary Dysplasia in Extremely Preterm Neonates: A Study Protocol for a Placebo-Controlled Randomized Multicenter Trial [NCT04440670]

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