Effects of cytokines and chemokines on migration of mesenchymal stem cells following spinal cord injury

We investigated the effects of cytokines and chemokines and their associated signaling pathways on mesenchymal stem cell migration after spinal cord injury, to determine their roles in the curative effects of mesenchymal stem cells. This study reviewed the effects of tumor necrosis factor-α, vascular endothelial growth factor, hepatocyte growth factor, platelet-derived growth factor, basic fibroblast growth factor, insulin like growth factor-I, stromal cell-derived factor and monocyte chemoattractant protein-1, 3 during mesenchymal stem cell migration to damaged sites, and analyzed the signal transduction pathways involved in their effects on mesenchymal stem cell migration. The results confirmed that phosphatidylinositol 3-kinase/serine/threonine protein kinases and nuclear factor-KB play crucial roles in the migration of mesenchymal stem cells induced by cytokines and chemokines.

Mesenchymal stem/stromal cells as adjuvant therapy in COVID-19- associated acute lung injury and cytokine storm: Importance of cell identification

Theoretically, mesenchymal stem cells (MSCs) are very promising as adjuvanttherapy to alleviate coronavirus disease 2019 (COVID-19)-associated acute lunginjury and cytokine storm. Several published studies, which used MSCs toalleviate COVID-19-associated acute lung injury and cytokine storm, reportedpromising results. However, the evidence came from a case report, case series,and clinical trials with a limited number of participants. Therefore, more studiesare needed to get robust proof of MSC beneficial effects.

Protective effect of thodioloside and bone marrow mesenchymal stem cells infected with HIF-1-expressing adenovirus on acute spinal cord injury

Rhodioloside has been shown to protect cells from hypoxia injury,and bone marrow mesenchymal stem cells have a good effect on tissue repair.To study the effects of rhodioloside and bone marrow mesenchymal stem cells on spinal cord injury,a rat model of spinal cord injury was established using the Infinite Horizons method.After establishing the model,the rats were randomly divided into five groups.Rats in the control group were intragastrically injected with phosphate buffered saline(PBS)(5μL).PBS was injected at 6 equidistant points around 5 mm from the injury site and at a depth of 5 mm.Rats in the rhodioloside group were intragastrically injected with rhodioloside(5 g/kg)and intramuscularly injected with PBS.Rats in the mesenchymal stem cell(MSC)group were intramuscularly injected with PBS and intramuscularly with MSCs(8×10^6/mL in a 50-μL cell suspension).Rats in the Ad-HIF-MSC group were intragastrically injected with PBS and intramuscularly injected with HIF-1 adenovirus-infected MSCs.Rats in the rhodioloside+Ad-HIF-MSC group were intramuscularly injected with MSCs infected with the HIF-1 adenovirus and intragastrically injected with rhodioloside.One week after treatment,exercise recovery was evaluated with a modified combined behavioral score scale.Hematoxylin-eosin staining and Pischingert’s methylene blue staining were used to detect any histological or pathological changes in spinal cord tissue.Levels of adenovirus IX and Sry mRNA were detected by real-time quantitative polymerase chain reaction and used to determine the number of adenovirus and mesenchymal stem cells that were transfected into the spinal cord.Immunohistochemical staining was applied to detect HIF-1 protein levels in the spinal cord.The results showed that:(1)compared with the other groups,the rhodioloside+Ad-HIF-MSC group exhibited the highest combined behavioral score(P<0.05),the most recovered tissue,and the greatest number of neurons,as indicated by Pischingert’s methylene blue staining.(2)Compared with the PBS group,HIF-1 protein expression was greater in the rhodioloside group(P<0.05).(3)Compared with the Ad-HIF-MSC group,Sry mRNA levels were higher in the rhodioloside+Ad-HIF-MSC group(P<0.05).These results confirm that rhodioloside combined with bone marrow mesenchymal stem cells can promote the recovery of spinal cord injury and activate the HIF-1 pathway to promote the survival of bone marrow mesenchymal stem cells and repair damaged neurons within spinal cord tissue.This experiment was approved by the Animal Ethics Committee of Gansu University of Traditional Chinese Medicine,China(approval No.2015KYLL029)in June 2015.

Potential advantages of acute kidney injury management by mesenchymal stem cells

Mesenchymal stem cells are currently considered as a promising tool for therapeutic application in acute kidney injury(AKI) management. AKI is characterized by acute tubular injury with rapid loss of renal function. After AKI, inflammation, oxidative stress and excessive deposition of extracellular matrix are the molecular events that ultimately cause the end-stage renal disease. Despite numerous improvement of supportive therapy, the mortality and morbidity among patients remain high. Therefore, exploring novel therapeutic options to treat AKI is mandatory. Numerous evidence in animal models has demonstrated the capability of mesenchymal stem cells(MSCs) to restore kidney function after induced kidney injury. After infusion, MSCs engraft in the injured tissue and release soluble factors and microvesicles that promote cell survival and tissue repairing. Indeed, the main mechanism of action of MSCs in tissue regeneration is the paracrine/endocrine secretion of bioactive molecules. MSCs can be isolated from several tissues, including bone marrow, adipose tissue, and blood cord; pre-treatment procedures to improve MSCs homing and their paracrine function have been also described. This review will focus on the application of cell therapy in AKI and it will summarize preclinical studies in animal models and clinical trials currently ongoing about the use of mesenchymal stem cells after AKI.

Could extracellular vesicles derived from mesenchymal stem cells be a potential therapy for acute pancreatitis-induced cardiac injury?

Acute pancreatitis(AP)often leads to a high incidence of cardiac injury,posing significant challenges in the treatment of severe AP and contributing to increased mortality rates.Mesenchymal stem cells(MSCs)release bioactive molecules that participate in various inflammatory diseases.Similarly,extracellular vesicles(EVs)secreted by MSCs have garnered extensive attention due to their comparable anti-inflammatory effects to MSCs and their potential to avoid risks associated with cell transplantation.Recently,the therapeutic potential of MSCs-EVs in various inflammatory diseases,including sepsis and AP,has gained increasing recognition.Although preclinical research on the utilization of MSCs-EVs in AP-induced cardiac injury is limited,several studies have demonstrated the positive effects of MSCs-EVs in regulating inflammation and immunity in sepsis-induced cardiac injury and cardiovascular diseases.Furthermore,clinical studies have been conducted on the therapeutic application of MSCs-EVs for some other diseases,wherein the contents of these EVs could be deliberately modified through prior modulation of MSCs.Consequently,we hypothesize that MSCs-EVs hold promise as a potential therapy for AP-induced cardiac injury.This paper aims to discuss this topic.However,additional research is essential to comprehensively elucidate the underlying mechanisms of MSCs-EVs in treating AP-induced cardiac injury,as well as to ascertain their safety and efficacy.

Local low-dose X-ray radiation promotes homing of mesenchymal stem cells to the injured mouse spinal cord

BACKGROUND： Bone marrow-derived mesenchymal stem cells （BMSCs） are a potentially useful source for cell replacement therapy following spinal cord injury. However, the homing characteristics of BMSCs in vivo remain unclear. Low-dose radiation has been shown to promote homing of BMSCs to exposed sites. OBJECTIVE： To investigate the effects of low-dose local radiation to non-injured areas on the ability of human BMSCs to home to the injured mouse spinal cord, as well as recovery of spinal cord injury. DESIGN, TIME AND SE＇I-FING： A randomized, controlled, animal experiment was performed at the Central Laboratory, Second Affiliated Hospital of Soochow University between October 2007 and October 2008. MATERIALS： BMSCs were isolated from four adult, human donors. METHODS： Fifty adult, female, Balb/c mice were subjected to adjusted weight-drop impact resulting in complete paraplegia. Three days later, mice were randomly assigned to a radiation ＋ transplantation group （n = 23） and a transplantation group （n = 20）. In total, 2 x 106 carboxyfluorescein diacetate succinimidyl ester-labeled BMSCs were injected into each mouse via the caudal vein. Mice in the radiation ＋ transplantation group received 2.5 Gy local X-ray irradiation 2 hours before BMSCs injection. MAIN OUTCOME MEASURES： The homing of BMSCs to injured cord and irradiated skin after transplantation was observed by fluorescence microscope; the structure recovery of injured cord was assessed by magnetic resonance imaging. RESULTS： Compared with the transplantation group, at 24 hours after transplantation, the number of BMSCs was significantly increased in the injured area and the exposed site （P 〈 0.05）, and inflammation and edema were significantly alleviated in the injured cord in the radiation ＋ transplantation group. CONCLUSION： Local low-dose radiation has the potential to promote homing of BMSCs and recovery of spinal cord injury, although the radiated region was not injured area.

The mechanism by which exosomes derived from bone marrow mesenchymal stem cells promote the regeneration of renal tubules in acute kidney injury through the regulation of the PTEN signaling pathway by miR-21

Acute kidney injury(AKI)is a significant global health issue with limited current treatment options.This study focused on the mechanism by which exosomes derived from bone marrow mesenchymal stem cells(BMSCs)promote renal tubule regeneration in AKI through the regulation of the PTEN signaling pathway by miR-21.BMSCs were isolated and characterized,and their exosomes were purified.In vitro,renal tubular epithelial cell injury models were established,and the co-culture of exosomes and cells demonstrated enhanced cell proliferation and reduced apoptosis.In vivo,AKI animal models showed improved renal function and histopathological changes after exosome treatment.miR-21 was found to be upregulated in exosomes and recipient cells,targeting PTEN and activating the PI3K/AKT pathway.The signaling network also interacted with other pathways related to renal tubule regeneration.The study highlights the potential of exosome therapy for AKI and provides insights into the underlying molecular mechanisms,although further research is needed to address remaining challenges and translate these findings into clinical applications.

Intravenous transplantation of mesenchymal stem cells attenuates oleic acid induced acute lung injury in rats

Background Acute lung injury （ALl） and end-stage acute respiratory distress syndrome （ARDS） were among the most common causes of death in intensive care units. The activation of an inflammatory response and the damage of pulmonary epithelium and endotheliumwerethe hallmark of ALI/ARDS. Recent studies had demonstrated the importance of mesenchymal stem cells （MSCs） in maintaining the normal pulmonary endothelial and epithelial function as well as participating in modulating the inflammatory response and they are involved in epithelial and endothelial repair after injury. Here, our study demonstrates MSCs therapeutic potential in a rat model of ALI/ARDS. Methods Bone marrow derived MSCs were obtained from Sprague-Dawley （SD） rats and their differential potential was verified. ALl was induced in rats byoleic acid （OA）, and MSCs were transplanted intravenously. The lung injury and the concentration of cytokines in plasma and lung tissue extracts were assessed at 8 hours, 24 hours and 48 hours after OA-injection. Results The histological appearance and water content in rat lung tissue were significantly improved at different time points in rats treated with MSCs. The concentration of tumor necrosis factor-a and intercellular adhesion molecular-1 in rats plasma and lung tissue extracts were significantly inhibited after intravenous transplantation of MSCs, whereas interleukin-10 was significantly higher after MSCs transplantation at 8 hours, 24 hours and 48 hours after OA-challenge. Conclusions Intravenous transplantation of MSCs could maintain the integrity of the pulmonary alveolar-capillary barrier and modulate the inflammatory response to attenuate the experimental ALI/ARDS. Transplantation of MSCs could be a novel cell-based therapeutic strategy for prevention and treatment of ALI/ARDS.

Effect of Chinese Materia Medica with Tonifying Kidney Function on Transplantation of Multipotency Mesenchymal Stem Cells from Human Umbilical Cord in Mice Model of Acute Kidney Injury

Objective Mesenchymal stem cells（MSCs） represent a promising population for supporting new clinical concepts in cellular therapy, and they can be reprogrammed into induced pluripotent stem cells（iPSCs） by defined factors. Methods This method opened up a new era of stem cell research, because the transplantation rejection of iPSCs is the bottleneck of its clinical application, so seeking alternative compounds and animal origin diagnostic reagents to achieve full chemical iPSCs is to be done to solve this problem. Results The application of these iPSCs has largely been associated with well known undesirable effects such as the development of cancers in certain experimental models. This has called for the search and use of reprogramming factors that are safe. Chinese materia medica（CMM） with tonifying kidney function（TKF） offers an alternative source. On the other hand, human umbilical cord mesenchymal stem cells（hUMSCs） are known to be a ＂young＂ source of MSCs, hUMSCs transplantation is an attractive approach for acute kidney injury repair. Therefore, In this study, we investigated whether the treatment of CMM with TKF on hUMSCs could enhance the repair in mice model of acute kidney injury after transplantation. Conclusion Our results showed that the treatment of hUMSCs with kidney tonifying CMM increased their multipotency, improved the renal function of mice and enhanced subsequent homing to the injured kidney in an acute kidney injury mice model.

Effects of leptin-modified human placenta-derived mesenchymal stem cells on angiogenic potential and peripheral inflammation of human umbilical vein endothelial cells(HUVECs) after X-ray radiation

Combined radiation-wound injury(CRWI) is characterized by blood vessel damage and pro-inflammatory cytokine deficiency. Studies have identified that the direct application of leptin plays a significant role in angiogenesis and inflammation. We established a sustained and stable leptin expression system to study the mechanism. A lentivirus method was employed to explore the angiogenic potential and peripheral inflammation of irradiated human umbilical vein endothelial cells(HUVECs). Leptin was transfected into human placenta-derived mesenchymal stem cells(HPMSCs) with lentiviral vectors. HUVECs were irradiated by X-ray at a single dose of 20 Gy. Transwell migration assay was performed to assess the migration of irradiated HUVECs. Based on the Transwell systems, co-culture systems of HPMSCs and irradiated HUVECs were established. Cell proliferation was measured by cell counting kit-8(CCK-8) assay. The secretion of pro-inflammatory cytokines(human granulocyte macrophage-colony stimulating factor(GM-CSF), interleukin(IL)-1α, IL-6, and IL-8) was detected by enzyme-linked immunosorbent assay(ELISA). The expression of pro-angiogenic factors(vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(b FGF)) mRNA was detected by real-time quantitative polymerase chain reaction(RT-qPCR) assay. Relevant molecules of the nuclear factor-κB(NF-κB) and Janus kinase(JAK)/signal transducer and activator of transcription(STAT) signaling pathways were detected by western blot assay. Results showed that leptin-modified HPMSCs(HPMSCs/leptin) exhibited better cell proliferation, migration, and angiogenic potential(expressed more VEGF and bFGF). In both the single HPMSCs/leptin and the co-culture systems of HPMSCs/leptin and irradiated HUVECs, the increased secretion of pro-inflammatory cytokines(human GM-CSF, IL-1α, and IL-6) was associated with the interaction of the NF-κB and JAK/STAT signaling pathways. We conclude that HPMSCs/leptin could promote angiogenic potential and peripheral inflammation of HUVECs after X-ray radiation.

Mesenchymal stem cell-derived exosomes regulate microglia phenotypes:a promising treatment for acute central nervous system injury

There is growing evidence that long-term central nervous system(CNS)inflammation exacerbates secondary deterioration of brain structures and functions and is one of the major determinants of disease outcome and progression.In acute CNS injury,brain microglia are among the first cells to respond and play a critical role in neural repair and regeneration.However,microglial activation can also impede CNS repair and amplify tissue damage,and phenotypic transformation may be responsible for this dual role.Mesenchymal stem cell(MSC)-derived exosomes(Exos)are promising therapeutic agents for the treatment of acute CNS injuries due to their immunomodulatory and regenerative properties.MSC-Exos are nanoscale membrane vesicles that are actively released by cells and are used clinically as circulating biomarkers for disease diagnosis and prognosis.MSC-Exos can be neuroprotective in several acute CNS models,including for stroke and traumatic brain injury,showing great clinical potential.This review summarized the classification of acute CNS injury disorders and discussed the prominent role of microglial activation in acute CNS inflammation and the specific role of MSC-Exos in regulating pro-inflammatory microglia in neuroinflammatory repair following acute CNS injury.Finally,this review explored the potential mechanisms and factors associated with MSCExos in modulating the phenotypic balance of microglia,focusing on the interplay between CNS inflammation,the brain,and injury aspects,with an emphasis on potential strategies and therapeutic interventions for improving functional recovery from early CNS inflammation caused by acute CNS injury.

Mesenchymal stem cell therapy for acute radiation syndrome: Innovative medical approaches in military medicine

After a radiological or nuclear event, acute radiation syndrome(ARS) will present complex medical challenges that could involve the treatment of hundreds to thousands of patients. Current medical doctrine is based on limited clinical data and remains inadequate. Efforts to develop medical innovations that address ARS complications are unlikely to be generated by the industry because of market uncertainties specific to this type of injury. A prospective strategy could be the integration of cellular therapy to meet the medical demands of ARS. The most clinically advanced cellular therapy to date is the administration of mesenchymal stem cells(MSCs). Results of currently published investigations describing MSC safety and efficacy in a variety of injury and disease models demonstrate the unique qualities of this reparative cell population in adapting to the specific requirements of the damaged tissue in which the cells integrate. This report puts forward a rationale for the further evaluation of MSC therapy to address the current unmet medical needs of ARS. We propose that the exploration of this novel therapy for the treatment of the multivariate complications of ARS could be of invaluable benefit to military medicine.

Mesenchymal stem cell therapy for acute radiation syndrome

Acute radiation syndrome affects military personnel and civilians following the uncontrolled dispersal of radiation,such as that caused by detonation of nuclear devices and inappropriate medical treatments.Therefore,there is a growing need for medical interventions that facilitate the improved recovery of victims and patients.One promising approach may be cell therapy,which,when appropriately implemented,may facilitate recovery from whole body injuries.This editorial highlights the current knowledge regarding the use of mesenchymal stem cells for the treatment of acute radiation syndrome,the benefits and limitations of which are under investigation.Establishing successful therapies for acute radiation syndrome may require using such a therapeutic approach in addition to conventional approaches.

Mesenchymal stem cells as living anti-inflammatory therapy for COVID-19 related acute respiratory distress syndrome

Coronavirus disease 2019(COVID-19),a pandemic disease caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV2),is growing at an exponential rate worldwide.Manifestations of this disease are heterogeneous;however,advanced cases often exhibit various acute respiratory distress syndrome-like symptoms,systemic inflammatory reactions,coagulopathy,and organ involvements.A common theme in advanced COVID-19 is unrestrained immune activation,classically referred to as a“cytokine storm”,as well as deficiencies in immune regulatory mechanisms such as T regulatory cells.While mesenchymal stem cells(MSCs)themselves are objects of cytokine regulation,they can secrete cytokines to modulate immune cells by inducing antiinflammatory regulatory Treg cells,macrophages and neutrophils;and by reducing the activation of T and B cells,dendritic and nature killer cells.Consequently,they have therapeutic potential for treating severe cases of COVID-19.Here we discuss the unique ability of MSCs,to act as a“living antiinflammatory”,which can“rebalance”the cytokine/immune responses to restore equilibrium.We also discuss current MSC trials and present different concepts for optimization of MSC therapy in patients with COVID-19 acute respiratory distress syndrome.

Therapeutic prospects of mesenchymal stem/stromal cells in COVID-19 associated pulmonary diseases:From bench to bedside

The ongoing outbreak of coronavirus disease 2019(COVID-19)caused by the novel severe acute respiratory syndrome coronavirus 2 has become a sudden public emergency of international concern and seriously threatens millions of people’s life health.Two current studies have indicated a favorable role for mesenchymal stem/stromal cells(MSCs)in clinical remission of COVID-19 associated pulmonary diseases,yet the systematical elaboration of the therapeutics and underlying mechanism is far from satisfaction.In the present review,we summarize the therapeutic potential of MSCs in COVID-19 associated pulmonary diseases such as pneumonia induced acute lung injury,acute respiratory distress syndrome,and pulmonary fibrosis.Furthermore,we review the underlying mechanism of MSCs including direct-and trans-differentiation,autocrine and paracrine anti-inflammatory effects,homing,and neovascularization,as well as constitutive microenvironment.Finally,we discuss the prospects and supervision of MSC-based cytotherapy for COVID-19 management before large-scale application in clinical practice.Collectively,this review supplies overwhelming new references for understanding the landscapes of MSCs in the remission of COVID-19 associated pulmonary diseases.

Mesenchymal stem cells and COVID-19: What they do and what they can do

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) orcoronavirus disease 2019 (COVID-19) pandemic has exhausted the health systemsin many countries with thousands cases diagnosed daily. The currently usedtreatment guideline is to manage the common symptoms like fever and cough,but doesn’t target the virus itself or halts serious complications arising from thisviral infection. Currently, SARS-CoV-2 exhibits many genetic modulations whichhave been associated with the appearance of highly contagious strains. Thenumber of critical cases of COVID-19 increases markedly, and many of theinfected people die as a result of respiratory failure and multiple organ dysfunction. The regenerative potential of mesenchymal stem cells (MSCs) has beenextensively studied and confirmed. The impressive immunomodulation and antiinflammatoryactivity of MSCs have been recognized as a golden opportunity forthe treatment of COVID-19 and its associated complications. Moreover, MSCsregenerative and repairing abilities have been corroborated by many studies withpositive outcomes and high recovery rates. Based on that, MSCs infusion could bean effective mechanism in managing and stemming the serious complications andmultiple organ failure associated with COVID-19. In the present review, wediscuss the commonly reported complications of COVID-19 viral infection and theestablished and anticipated role of MSCs in managing these complications.

Potential for a pluripotent adult stem cell treatment for acute radiation sickness

Accidental radiation exposure and the threat of deliberate radiation exposure have been in the news and are a public health concern. Experience with acute radiation sickness has been gathered from atomic blast survivors of Hiroshima and Nagasaki and from civilian nuclear accidents as well as experience gained during the development of radiation therapy for cancer. This paper reviews the medical treatment reports relevant to acute radiation sickness among the survivors of atomic weapons at Hiroshima and Nagasaki, among the victims of Chernobyl, and the two cases described so far from the Fukushima Dai-Ichi disaster. The data supporting the use of hematopoietic stem cell transplantation and the new efforts to expand stem cell populations ex vivo for infusion to treat bone marrow failure are reviewed. Hematopoietic stem cells derived from bone marrow or blood have a broad ability to repair and replace radiation induced damaged blood and immune cell production and may promote blood vessel formation and tissue repair. Additionally, a constituent of bone marrow-derived, adult pluripotent stem cells, very small embryonic like stem cells, are highly resistant to ioniz-ing radiation and appear capable of regenerating radiation damaged tissue including skin, gut and lung.

Research progress of transfering mitochondria application in nanotubes in treatment of acute lung injury sepsis

Acute lung injury (ALI) is a common complication of sepsis with characteristics of acute onset, rapid change in the disease and high mortality. Since current clinical treatment can only alleviate the unfavorable condition to a certain extent but cure, we urgently need to find an effective treatment. Most scholars believe that sepsis-induced ALI is associated with extensive mitochondrial damage. In recent years, a widely studied pluripotent stem cell that is mesenchymal stem cell has been proved to alleviate and treat sepsis-induced ALI by transporting mitochondria via nanotubes in a microtubule-dependent manner. Research progress in this field will be reviewed in this study.

Extracellular vesicles in the pathogenesis and treatment of acute lung injury

Acute lung injury(ALI)and acute respiratory distress syndrome(ARDS)are common life-threatening lung diseases associated with acute and severe inflammation.Both have high mortality rates,and despite decades of research on clinical ALI/ARDS,there are no effective therapeutic strategies.Disruption of alveolar-capillary barrier integrity or activation of inflammatory responses leads to lung inflammation and injury.Recently,studies on the role of extracellular vesicles(EVs)in regulating normal and pathophysiologic cell activities,including inflammation and injury responses,have attracted attention.Injured and dysfunctional cells often secrete EVs into serum or bronchoalveolar lavage fluid with altered cargoes,which can be used to diagnose and predict the development of ALI/ARDS.EVs secreted by mesenchymal stem cells can also attenuate inflammatory reactions associated with cell dysfunction and injury to preserve or restore cell function,and thereby promote cell proliferation and tissue regeneration.This review focuses on the roles of EVs in the pathogenesis of pulmonary inflammation,particularly ALI/ARDS.

人脐带间充质干细胞抑制脓毒症小鼠肺组织细胞的焦亡

背景:急性肺损伤是脓毒症患者的常见严重并发症,其发病机制复杂,目前尚无有效的药物治疗方案。人脐带间充质干细胞通过抑制细胞过度焦亡从而改善脓毒症急性肺损伤的作用机制愈发受到重视。目的:探索人脐带间充质干细胞对脓毒症所致急性肺损伤小鼠肺组织细胞焦亡的影响及机制。方法:48只Balb/c雄性小鼠按随机数字法分为假手术组、模型组、治疗组(n=16)。模型组、治疗组行盲肠结扎穿孔建立脓毒症所致急性肺损伤模型,假手术组仅开腹后缝合。治疗组术后6 h尾静脉注射200μL人脐带间充质干细胞悬液(5×105个细胞),模型组及假手术组术后6 h尾静脉注射200μL生理盐水。术后28 h,各组随机取5只小鼠予以尾静脉注射伊文思蓝检测肺血管通透性;收集各组剩余小鼠肺泡灌洗液和肺组织,ELISA检测肺泡灌洗液中白细胞介素1β、白细胞介素18水平,计数肺泡灌洗液中细胞总数及巨噬细胞数;苏木精-伊红染色观察肺组织病理学形态,TUNEL染色观察肺组织细胞焦亡情况,RT-PCR、Western blot检测肺组织中Toll样受体4、GSDMD及Caspase-11的mRNA和蛋白表达。结果与结论:与模型组相比,治疗组术后28 h肺血管通透性显著下降(P<0.05),肺泡灌洗液中白细胞介素1β、白细胞介素18水平降低(P<0.05),细胞总数及巨噬细胞数降低(P<0.05),肺损伤程度减轻,肺组织细胞焦亡指数降低(P<0.05),肺组织Toll样受体4、GSDMD、GSDMD-N及Caspase-11 mRNA及蛋白表达水平均显著下降(P<0.05)。结果表明,人脐带间充质干细胞可能通过抑制Toll样受体4/Caspase-11/GSDMD信号通路活化,改善肺组织细胞焦亡,从而在一定程度上改善脓毒症小鼠肺损伤的严重程度。