维甲酸联合神经生长因子体外诱导人脐血间充质干细胞向神经样细胞定向分化的实验研究

目的:探讨脐血间充质干细胞(MSCs)向神经样细胞定向诱导分化的条件及方法,以明确其神经分化潜能。方法:将人脐血间充质干细胞体外培养扩增、保存后,取第5代的MSCs分别用维甲酸(RA)、维甲酸联合神经生长因子(NGF)诱导方法向神经样细胞诱导,诱导分化期间观察细胞形态变化,并比较表达神经元特异性烯醇化酶(NES)mRNA、胶质纤维酸性蛋白(GFAP)mRNA的差异。结果:两种不同诱导方法均能诱导细胞发生典型变化,对照组未发现神经样细胞生长。免疫组化法显示三种诱导方法诱导后均表达Nestin、NSE、GFAP,NGF+RA组多于RA组。Real-time RT-PCR显示诱导组及对照组均有NSE mRNA、GFAP mRNA表达,但两种诱导方法诱导后表达上调(P<0.05),添加NGF较单纯RA组上调明显(P<0.05)。结论:脐血MSCs经两种神经营养因子诱导法均可分化为神经样细胞,并表达神经细胞特异性标志物,其中添加NGF后较单纯应用RA诱导效果好。

兔骨髓间充质干细胞体外分离培养及生长特性的初步研究

目的:探索兔骨髓间充质干细胞(MSC)体外分离及培养扩增的方法。方法:骨髓穿刺法抽取雄性新西兰白兔髂骨骨髓5ml,联合应用密度梯度离心及贴壁培养法分离纯化MSC并进行体外扩增,倒置显微镜下观察原代及传代细胞的形态、生长情况,计数细胞数目,绘制细胞生长曲线。HE染色光镜观察细胞形态。结果:成功建立了兔MSC体外分离及培养扩增的方法,生长动力学分析发现,传代细胞随传代次数的增加,增殖能力逐渐下降。结论:兔MSC能在体外成功培养、扩增,可作为组织工程的种子细胞。

大鼠骨髓间充质干细胞在淋巴细胞增殖中的免疫调节作用

目的:探讨大鼠骨髓间充质干细胞(BM MSCs)在体外对淋巴细胞增殖的影响及其作用机制。方法:分离和鉴定大鼠MSCs,与淋巴细胞、BRL、刀豆蛋白(ConA)建立共培养体系,混合培养0h、24h和48h后,用ELISA方法检测上清中TNF-α、TGF-β和IL-10的分泌量,MTT方法检测淋巴细胞数目变化,流式细胞仪检测调节T细胞(Treg)的含量变化。结果:加入MSCs后TNF-α分泌量降低,TGF-β和IL-10分泌量升高,OD值明显低于未加MSCs组的对照组(P<0.05),Treg含量升高。结论:骨髓MSCs在单独存在以及与BRL同时存在时均对淋巴细胞的增殖具有抑制作用,并且作用程度随时间变化不明显,其中IL-10、TGF-β以及Treg参与了这种免疫抑制过程。

骨质颗粒分离培养间充质细胞的实验研究

目的:为探索间充质干细胞更广泛的来源。方法:选择了正常人骨髓,急性粒细胞性白血病缓解期患者骨髓、再生障碍性贫血患者骨髓、脐带血和骨质颗粒等5种标本来源。采用贴壁法和特殊的干细胞培养基/间充质干细胞刺激因子分离、纯化MSCs,观察比较不同来源MSCs的体外生长特性,流式细胞术检测培养细胞的CD105。结果:正常人骨髓、急性粒细胞性白血病缓解期患者骨髓和骨质颗粒标本均能培养出MSCs,从骨质颗粒得到的MSCs数量较多。脐带血和再生障碍性贫血患者骨髓标本没有培养出MSCs。培养的MSCs均一地表达CD105。结论:在体外培养人类正常骨髓和急性粒细胞性白血病缓解期的骨髓均可以得到MSCs,两种样本分离培养得到的MSCs在形态学、表面标志、增殖特性等方面没有显著差异。从人类骨质颗粒得到的MSCs的生长从数量上优于从骨髓中获得的MSCs。

Comprehensive Understanding of Immune Cells in The Pathogenesis of Non-alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,defined by several phases,ranging from benign fat accumulation to non-alcoholic steatohepatitis(NASH),which can lead to liver cancer and cirrhosis.Although NAFLD is a disease of disordered metabolism,it also involves several immune cell-mediated inflammatory processes,either promoting and/or suppressing hepatocyte inflammation through the secretion of pro-inflammatory and/or anti-inflammatory factors to influence the NAFLD process.However,the underlying disease mechanism and the role of immune cells in NAFLD are still under investigation,leaving many open-ended questions.In this review,we presented the recent concepts about the interplay of immune cells in the onset and pathogenesis of NAFLD.We also highlighted the specific non-immune cells exhibiting immunological properties of therapeutic significance in NAFLD.We hope that this review will help guide the development of future NAFLD therapeutics.

A Review on the Biological Characteristics and Secretory Functions of Adipose-derived Mesenchymal Stem Cells

Adipose-derived mesenchymal stem cells （ADSCs） can be largely and easily obtained from a wide range of sources. Moreover, they have self-renewal ability, multi-differentiation potential, and an important role in immune regulation. They can secrete a variety of cytokines to regulate the in vivo micro-environment. Therefore, ADSCs are the ideal seed ceils for stem ceils application. This paper reviews the location, isolation, surface markers, proliferation, differentiation and other biological characteristics of ADSCs, as well as their secretory function and relative researches. ADSCs are expected to become excellent seed cells for cell therapy and tissue engineering through in-depth studies.

Rat bone marrow mesenchymal stem cells differentiate into hepatocytes in vitro

AIM: To investigate the mechanism and regulation of differentiation from bone marrow mesenchymal stem cells (MSCs) into hepatocytes and to find a new source of celltypes for therapies of hepatic diseases. METHODS: MSCs were isolated by combining gradient density centrifugation with plastic adherence. The cells were cultured in osteogenic or adipogenic differentiation medium and determined by histochemical staining. MSCs were plated in plastic culture flasks that were not coated with components of extracellular matrix (ECM). When MSCs reached 70% confluence, they were cultured in low glucose Dulbecco's modified Eagle's medium supplemented with 10 mL/L fetal bovine serum, 20 ng/mL hepatocyte growth factor (HGF) and 10 ng/mL fibroblast growth factor-4 (FGF-4). The medium was changed every 3 d and stored for albumin, alpha-fetoprotein (AFP) and urea assay. Glycogen store of hepatocytes was determined by periodic acid-Schiff staining.RESULTS: By combining gradient density centrifugation with plastic adherence, we isolated a homogeneous population of cells from rat bone marrow and differentiated them into osteocytes and adipocytes. When MSCs were cultured withFGF-4 and HGF, approximately 56.6% of cells became smallround and epithelioid on d 24 by morphology. Compared with the control, levels of AFP increased significantly from d 12 to 15.5±1.4 μg/L (t = 2.31, P＜0.05) in MSCs cultured with FGF-4and HGF, and were higher (46.2±1.5 μg/L)ond 21 (t = 41.926, P＜0.01), then decreased to 24.8±2.2 μg/L on d 24 (t = 10.345, P＜0.01). Albumin increased significantly on d 21 (t= 3.325, P＜0.01) to 1.4±0.2 μg/mL,and to 2.1±0.7 μg/mL on d 24 (t= 3.646, P＜0.01). Urea(2.3±0.4 mmol/L) was first detected on d 21 (t = 6.739, P＜0.01), and continued to increase to 2.6±0.9 mmol/Lon d 24 (t= 4.753, P＜0.01). Glycogen storage was first seen on d 21.CONCLUSION: The method combining gradient density centrifugation with plastic adherence can isolate MSCs. Rat MSCs may be differentiated into hepatocytes by FGF-4 and HGF. Cytokines may play a more important role in differentiation from rat MSCs into hepatocytes.

Intravenous injection of mesenchymal stem cells is effective in treating liver fibrosis

AIM: To compare the influence of different transplant sites in bone marrow mesenchymal stem cell (MSC)-based therapy for liver fibrosis. METHODS: MSCs isolated from Sprague Dawley (SD) rats were induced into hepatocyte-like cells. Liver fibrosis in SD rats was induced with carbon tetrachloride. Following hepatocyte induction in vitro, 4',6-diamidino- 2-phenylindole (DAPI)-labeled MSCs were transplanted by intravenous, intrahepatic, and intraperitoneal injection. Histopathological staining, immunohistochemistry, and biochemical analysis were used to compare the morphological and functional liver regeneration among different MSC injection modalities. The expression differences of interleukins, growth factor, extracellular matrix, matrix metalloproteinases, and tissue inhibitor of metalloproteinase were examined by real-time reverse transcription-polymerase chain reaction (RT-PCR) andenzyme linked immunosorbent assay (ELISA). RESULTS: Four days after exposure to hepatocyte differentiation medium, MSCs that did not express hepatocyte markers could express α-fetoprotein, albumin, and cytokeratin 18. The results of histopathological staining, immunohistochemistry, and biochemical analysis indicated that intravenous injection is more effective at rescuing liver failure than other injection modalities. DAPI-labeled cells were found around liver lobules in all three injection site groups, but the intravenous group had the highest number of cells. PCR and ELISA analysis indicated that interleukin-10 (IL-10) was highest in the intravenous group, whereas il1β, il6, tnfα and tgfβ, which can be regulated by IL10 and are promoters of liver fibrosis, were significantly lower than in the other groups. CONCLUSION: MSC administration is able to protect against liver fibrosis. Intravenous injection is the most favorable treatment modality through promotion of IL10 expression.

Bone marrow mesenchymal stem cell transplantation combined with perindopril treatment attenuates infarction remodelling in a rat model of acute myocardial infarction

Objective: This study was performed to evaluate whether implantation of mesenchymal stem cell (MSC) would reduce left ventricular remodelling from the molecular mechanisms compared with angiotensin-converting enzyme inhibitors (ACEIs) perindopril into ischemic myocardium after acute myocardial infarction. Methods: Forty rats were divided into four groups: control, MSC, ACEI, MSC+ACEI groups. Bone marrow stem cell derived rat was injected immediately into a zone made ischemic by coronary artery ligation in MSC group and MSC+ACEI group. Phosphate-buffered saline (PBS) was injected into control group. Perindopril was administered p.o. to ACEI group and MSC+ACEI group. Six weeks after implantation, the rats were killed and heart sample was collected. Fibrillar collagen was observed by meliorative Masson’s trichome stain. Western Blotting was employed to evaluate the protein expression of matrix metalloproteinase (MMP)-2, matrix metalloproteinase (MMP)-9 in infarction zone. The transcriptional level of MMP2, MMP9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 in infarction area was detected by reverse transcriptase PCR (RT-PCR) analysis. Results: The fibrillar collagen area, the protein expression of MMP2, MMP9 and the transcriptional level of MMP2, MMP9 mRNA in infarction zone reduced in MSC group, ACEI group, and MSC+ACEI group. No significant difference was detected in the expression of TIMP1 mRNA among the 4 groups. Conclusion: Both MSC and ACEI could reduce infarction remodelling by altering collagen metabolism.

Culture and Identification of Human Amniotic Mesenchymal Stem Cells

Objective To establish the method of isolation, purification, and identification of human amniotic mesenchymal stem cells (hAMSCs). Methods hAMSCs were isolated from human amniotic membrane by trypsin-collagenase digestion, and cultured in Dulbecco's modified Eagle's medinm/F12 medium supplemented with 10% fetal bovine serum. Phenotypic characteristics of these cells were analyzed by means of immunocytochemistry and flow cytometry. Results The cells successfully isolated from human amniotic membrane expressed representative mesenchymal cell surface markers CD44, CD90, and vimentin, but not CD45. Conclusions This study establishes a potential method for isolation of hAMSCs from human amnion, in vitro culture, and identification. The isolated cells show phenotypic characteristics of mesenchymal stem cells.

Cognitive improvement following transvenous adipose-derived mesenchymal stem cell transplantation in a rat model of traumatic brain injury

The effects of adipose-derived mesenchymal stem cell (ADMSC) transplantation for the repair of traumatic brain injury remain poorly understood. The present study observed neurological functional changes in a rat model of traumatic brain injury following ADMSC transplantation via the tail vein. Cell transplants were observed in injured cerebral cortex, and expression of brain-derived nerve growth factor was significantly increased in the injured hippocampus following transplantation. Results demonstrated that transvenous ADMSC transplants migrated to the injured cerebral cortex and significantly improved cognitive function.

Comparison of human amniotic fluid-derived and umbilical cord Wharton＇s Jelly-derived mesenchymal stromal cells： Characterization and myocardial differentiation capacity

Objective To compare the characterization and myocardial differentiation capacity of arnniotic fluid-derived mesenchymal stromal cells （AF MSCs） and umbilical cord Wharton＇s Jelly-derived mesenchymal stromal cells （WJ MSCs）. Methods The human AF MSCs were cultured from amniotic fluid samples obtained by amniocentesis. The umbilical cord WJ MSCs were obtained from Wharton＇s Jelly of umbilical cords of infants delivered full-term by normal labor. The morphology, growth curves, and analyses by flow cytometry of cell surface markers were compared between the two types of cells. Myocardial genes （GATA-4, c-TnT, a-actin, and Cx43） were detected by real-time PCR and the corresponding protein expressions were detected by Western blot analysis after myocardial induced in AF MSCs and WJ MSCs. Results Our findings revealed AF MSCs and WJ MSCs shared similar morphological characteristics of the fibroblastoid shape. The AF MSCs were easily obtained than the WJ MSCs and had a shorter time to reach adherence of 2.7 ± 1.6 days to WJ MSCs of 6.5 ± 1.8 days. The growth curves by MTT cytotoxic assay showed the AF MSCs had a similar proliferative capacity at passage 5 and passage 10. However, the proliferative capacities ofWJ MSCs were decreased at 5 passage relative to 10 passage. Both AF stem cells and WJ stem cells had the characteristics of mesenchymal stromal cells with some characteristics of embryonic stem cells. They express CD29 and CD105, but not CD34. They were positive for Class I major histocompatibility （MHC I） antigens （HLA-ABC）, and were negative, or mildly positive, for MHC Class II （HLA-DR） antigen. Oct-4 was positive in all the two cells types. Both AF MSCs and WJ MSCs could differentiate along myocardium. The differentiation capacities were detected by the expression of GATA-4, c-TnT, a-actin, Cx43 after myocardial induction. Conclusions Both AF MSCs and WJ MSCs have the potential clinical application for myogenesis in cardiac regenerative therapy.

Rubidium-modified bioactive glass-ceramics with hydroxyapatite crystals for bone regeneration

In order to study the influence of rubidium(Rb)addition on the phase composition,microstructure,mechanical properties and cell response of bioactive glass-ceramics,CaO−SiO2−Na2O−B2O3−MgO−ZnO−P2O5 glass system was designed with and without addition of Rb.The results show that hydroxyapatite(HA)and Mg−whitelockite(Ca18Mg2H2(PO4)14)crystalline phases are formed in the glass matrix without Rb.After the addition of Rb,only HA phase is detected.The grain size of the crystals in the glass-ceramics is larger with the addition of Rb than that of samples without Rb.Rb addition can improve the bending strength of glass-ceramics.The cultivation of human bone marrow mesenchymal stem cells(hBMSCs)on Rb-containing glass-ceramics demonstrates enhanced cell adhesion,proliferation and ALP activity.In conclusion,Rb-modified glass-ceramics exhibit good mechanical property,excellent bioactivity and biocompatibility,which have potential for bone regeneration application.

Mesenchymal stromal cells' role in tumor microenvironment:involvement of signaling pathways

Mesenchymal stromal cells(MSCs) are adult multipotent stem cells residing as pericytes in various tissues and organs where they can differentiate into specialized cells to replace dying cells and damaged tissues. These cells are commonly found at injury sites and in tumors that are known to behave like "wounds that do not heal." In this article, we discuss the mechanisms of MSCs in migrating, homing, and repairing injured tissues. We also review a number of reports showing that tumor microenvironment triggers plasticity mechanisms in MSCs to induce malignant neoplastic tissue formation, maintenance, and chemoresistance, as well as tumor growth. The antitumor properties and therapeutic potential of MSCs are also discussed.

Utility of co-transplanting mesenchymal stem cells in islet transplantation

Islet transplantation is characterized by the transplantation of isolated islets from donor pancreata into a diabetic recipient. Although it is a viable choice in the treatment of insulin dependent diabetes mellitus, most patients (approximately 90%) require insulin five years after transplantation. Recently, the co-transplantation of mesenchymal stem cells (MSCs) and islets in animal studies has revealed the effectiveness of MSCs co-transplantation for improving islet function. Themechanisms underlying the beneficial impact of MSCs include immunomodulation and the promotion of angiogenesis. In this review, we discuss MSCs and how they support improved graft survival and function.

Mesenchymal stromal cell-based therapy: Regulatory and translational aspects in gastroenterology

The past decade has witnessed an outstanding scientific production focused towards the possible clinical applications of mesenchymal stromal cells(MSCs) in autoimmune and chronic inflammatory diseases. This raised the need of novel standards to adequately address quality, efficacy and safety issues of this advanced therapy. The development of a streamlined regulation is currently hampered by the complexity of analyzing dynamic biological entities rather than chemicals. Although numerous pieces of evidence show efficacy in reducing intestinal inflammation, some inconsistencies between the mechanisms of action of rodent vs human MSCs suggest caution before assigning translational value to preclinical studies. Preliminary evidence from clinical trials showed efficacy of MSCs in the treatment of fistulizing Crohn's disease(CD), and preparations of heterologous MSCs for CD treatment are currently tested in ongoing clinical trials. However, safety issues, especially in longterm treatment, still require solid clinical data. In this regard, standardized guidelines for appropriate dosing and methods of infusion could enhance the likelihood to predict more accurately the number of responders and the duration of remission periods. In addition, elucidating MSC mechanisms of action could lead to novel and more reliable formulations such as those derived from the MSCs themselves(e.g., supernatants).

Effect of CXCR3/HO-1 genes modified bone marrow mesenchymal stem cells on small bowel transplant rejection

AIM To investigate whether bone marrow mesenchymal stem cells (BMMSCs) modified with the HO-1 and CXCR3 genes can augment the inhibitory effect of BMMSCs on small bowel transplant rejection. METHODS Lewis rat BMMSCs were cultured in vitro. Third-passage BMMSCs were transduced with the CXCR3 / HO-1 genes or the HO-1 gene alone. The rats were divided into six groups and rats in the experimental group were pretreated with BMMSCs 7 d prior to small bowel transplant. Six time points (instant, 1 d, 3 d, 7 d, 10 d, and 14 d) (n = 6) were chosen for each group. Hematoxylin-eosin staining was used to observe pathologic rejection, while immunohistochemistry and Western blot were used to detect protein expression. Flow cytometry was used to detect T lymphocytes and enzyme linked immunosorbent assay was used to detect cytokines. RESULTS The median survival time of BMMSCs from the CXCR3/HO-1 modified group (53 d) was significantly longer than that of the HO-1 modified BMMSCs group (39 d), the BMMSCs group (26 d), and the NS group (control group) (16 d) (P < 0.05). Compared with BMMSCs from the HO-1 modified BMMSCs, BMMSCs, and NS groups, rejection of the small bowel in the CXCR3 / HO-1 modified group was significantly reduced, while the weight of transplant recipients was also significantly decreased (P < 0.05). Furthermore, IL-2, IL-6, IL-17, IFN-gamma, and TNF-alpha levels were significantly decreased and the levels of IL-10 and TGF-beta were significantly increased (P < 0.05). CONCLUSION BMMSCs modified with the CXCR3 and HO-1 genes can abrogate the rejection of transplanted small bowel more effectively and significantly increase the survival time of rats that receive a small bowel transplant.

Mesenchymal stem cells rescue acute hepatic failure by polarizing M2 macrophages

AIM To investigate whether M1 or M2 polarization contributes to the therapeutic effects of mesenchymal stem cells(MSCs) in acute hepatic failure(AHF).METHODS MSCs were transfused into rats with AHF induced by D-galactosamine(DGal N). The therapeutic effects of MSCs were evaluated based on survival rate and hepatocyte proliferation and apoptosis. Hepatocyte regeneration capacity was evaluated by the expression of the hepatic progenitor surface marker epithelial cell adhesion molecule(Ep CAM). Macrophage polarization was analyzed by M1 markers [CD68,tumor necrosis factor alpha(TNF-α),interferon-γ(IFN-γ),inducible nitric oxide synthase(INOS)] and M2 markers [CD163,interleukin(IL)-4,IL-10,arginase-1(Arg-1)] in the survival and death groups after MSC transplantation.RESULTS The survival rate in the MSC-treated group was increased compared with the DPBS-treated control group(37.5% vs 10%). MSC treatment protected rats with AHF by reducing apoptotic hepatocytes and promoting hepatocyte regeneration. Immunohistochemical analysis showed that MSC treatment significantly increased the expression of Ep CAM compared with the control groups(P < 0.001). Expression of Ep CAM in the survival group was significantly up-regulated compared with the death group after MSC transplantation(P = 0.003). Transplantation of MSCs significantly improved the expression of CD163 and increased the gene expression of IL-10 and Arg-1 in the survival group. IL-4 concentrations were significantly increased compared to the death group after MSC transplantation(88.51 ± 24.51 pg/m L vs 34.61 ± 6.6 pg/m L,P < 0.001). In contrast,macrophages showed strong expression of CD68,TNF-α,and INOS in the death group. The concentration of IFN-γ was significantly increased compared to the survival group after MSC transplantation(542.11 ± 51.59 pg/m L vs 104.07 ± 42.80 pg/m L,P < 0.001).CONCLUSION M2 polarization contributes to the therapeutic effects of MSCs in AHF by altering levels of anti-inflammatory and pro-inflammatory factors.

Osteogenic composite nanocoating based on nanohydroxyapatite, strontium ranelate and polycaprolactone for titanium implants

Titanium and its alloys are commonly used as dental and bone implant materials.Biomimetic coating of titanium surfaces could improve their osteoinductive properties.In this work,we have developed a novel osteogenic composite nanocoating for titanium surfaces,which provides a natural environment for facilitating adhesion,proliferation,and osteogenic differentiation of bone marrow mesenchymal stem cells(MSCs).Electrospinning was used to produce composite nanofiber coatings based on polycaprolactone(PCL),nano-hydroxyapatite(nHAp)and strontium ranelate(SrRan).Thus,four types of coatings,i.e.,PCL,PCL/nHAp,PCL/SrRan,and PCL/nHAp/SrRan,were applied on titanium surfaces.To assess chemical,morphological and biological properties of the developed coatings,EDS,FTIR,XRD,XRF,SEM,AFM,in-vitro cytotoxicity and in-vitro hemocompatibility analyses were performed.Our findings have revealed that the composite nanocoatings were both cytocompatible and hemocompatible;thus PCL/HAp/SrRan composite nanofiber coating led to the highest cell viability.Osteogenic culture of MSCs on the nanocoatings led to the osteogenic differentiation of stem cells,confirmed by alkaline phosphatase activity and mineralization measurements.The findings support the notion that the proposed composite nanocoatings have the potential to promote new bone formation and enhance bone-implant integration.

Role of bone marrow-derived mesenchymal stem cells in a rat model of severe acute pancreatitis

AIM:To investigate the role and potential mechanisms of bone marrow mesenchymal stem cells(MSCs) in severe acute peritonitis(SAP).METHODS:Pancreatic acinar cells from Sprague Dawley rats were randomly divided into three groups:nonsodium deoxycholate(SDOC) group(non-SODC group),SDOC group,and a MSCs intervention group(i.e.,a co-culture system of MSCs and pancreatic acinar cells + SDOC).The cell survival rate,the concentration of malonaldehyde(MDA),the density of superoxide dismutase(SOD),serum amylase(AMS) secretion rate and lactate dehydrogenase(LDH) leakage rate were detected at various time points.In a separate study,Sprague Dawley rats were randomly divided into either an SAP group or an SAP + MSCs group.Serum AMS,MDA and SOD,interleukin(IL)-6,IL-10,and tumor necrosis factor(TNF)-α levels,intestinal mucosa injury scores and proliferating cells of small intestinal mucosa were measured at various time points after injecting either MSCs or saline into rats.In both studies,the protective effect of MSCs was evaluated.RESULTS:In vitro,The cell survival rate of pancreatic acinar cells and the density of SOD were significantly reduced,and the concentration of MDA,AMS secretion rate and LDH leakage rate were significantly increased in the SDOC group compared with the MSCs intervention group and the Non-SDOC group at each time point.In vivo,Serum AMS,IL-6,TNF-α and MAD level in the SAP + MSCs group were lower than the SAP group;however serum IL-10 level was higher than the SAP group.Serum SOD level was higher than the SAP group at each time point,whereas a significant betweengroup difference in SOD level was only noted after 24 h.Intestinal mucosa injury scores was significantly reduced and the proliferating cells of small intestinal mucosa became obvious after injecting MSCs.CONCLUSION:MSCs can effectively relieve injury to pancreatic acinar cells and small intestinal epithelium,promote the proliferation of enteric epithelium and repair of the mucosa,attenuate systemic inflammation in rats with SAP.