Nonalcoholic fatty liver disease （NAFLD） is an increasingly recognized cause of liver-related morbidity and mortality. It can develop secondary to numerous causes but a great majority of NAFLD cases occur in patient...Nonalcoholic fatty liver disease （NAFLD） is an increasingly recognized cause of liver-related morbidity and mortality. It can develop secondary to numerous causes but a great majority of NAFLD cases occur in patients who are obese or present with other components of metabolic syndrome （hypertension, dyslipidemia, diabetes）. This is called primary NAFLD and insulin resistance plays a key role in its pathogenesis. Obesity is characterized by expanded adipose tissue, which is under a state of chronic inflammation. This disturbs the normal storage and endocrine functions of adipose tissue. In obesity, the secretome （adipokines, oytokines, free fatty acids and other lipid moieties） of fatty tissue is amplified, which through its autocrine, paracrine actions in fat tissue and systemic effects especially in the liver leads to an altered metabolic state with insulin resistance （IR）. IR leads to hyperglycemia and reactive hyperinsulinemia, which stimulates lipid-accumulating processes and impairs hepatic lipid metabolism. IR enhances free fatty acid delivery to liver from the adipose tissue storage due to uninhibited lipolysis. These changes result in hepatic abnormal fat accumulation, which may initiate the hepatic IR and further aggravate the altered metabolic state of whole body. Hepatic steatosis can also be explained by the fact that there is enhanced dietary fat delivery and physical inactivity. IR and NAFLD are also seen in various lipodystrophic states in contrary to popular belief that these problems only occur due to excessive adiposity in obesity. Hence, altered physiology of adipose tissue is central to development of IR, metabolic syndrome and NAFLD.展开更多
BACKGROUND: Acute rejection after liver transplantation is usually treated with large doses of immunosuppressants with severe toxic and side-effects, so it is imperative to find a safe and effective method for prevent...BACKGROUND: Acute rejection after liver transplantation is usually treated with large doses of immunosuppressants with severe toxic and side-effects, so it is imperative to find a safe and effective method for preventing and treating rejection. This study was designed to confirm the immunomodulatory effects of rat mesenchymal stem cells (MSCs) in vitro and investigate the tolerogenic features in a rat model of allogeneic liver transplantation. METHODS: MSCs were isolated from adipose tissue of Sprague-Dawley (SD) rats and cultured. In vitro, MSCs were added into a mixed lymphocyte culture (MLC) system to study the inhibitory effects of MSCs on the proliferation of T lymphocytes in Wistar rats. By using SD and Wistar rats as liver donors and recipients, an orthotopic liver transplantation model was established and the rats were divided into a MSC-treated group and a blank control group. On postoperative day 7, all rats were sacrificed, and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), interleukin-2 (IL-2) and interleukin-10 (IL-10) were measured. The pathological changes of liver tissue and apoptosis of hepatocytes were also assessed. RESULTS: In in vitro MLC, T lymphocyte proliferation in Wistar rats was significantly inhibited by 48.44%. In the MSC-treated group, the levels of ALT, AST, TBIL, IL-2 and IL-10 were 134.2 +/- 45.0 U/L, 162.5 +/- 30.5 U/L, 30.6 +/- 5.4 mu mol/L, 187.35 +/- 18.26 mu g/L and 193.95 +/- 37.62 mu g/L, and those in the blank control group were 355.6 +/- 54.3 U/L, 296.4 +/- 71.2 U/L, 145.7 +/- 28.6 +/- mol/L, 295.73 +/- 57.15 mu g/L and 75.12 +/- 11.23 mu g/L, respectively, with statistically significant differences (P<0.05). Pathological examination revealed that the rejection in the MSC-treated group was clearly alleviated compared with that in the blank control group. TUNEL indicated that the apoptosis of hepatocytes in the MSC-treated group was milder than that in the blank control group (P<0.05). CONCLUSION: Adipose-derived MSC展开更多
Non-alcoholic fatty liver disease (NAFLD) comprising hepatic steatosis,non-alcoholic steatohepatitis (NASH),and progressive liver fibrosis is considered the most common liver disease in western countries.Fatty liver i...Non-alcoholic fatty liver disease (NAFLD) comprising hepatic steatosis,non-alcoholic steatohepatitis (NASH),and progressive liver fibrosis is considered the most common liver disease in western countries.Fatty liver is more prevalent in overweight than normal-weight people and liver fat positively correlates with hepatic insulin resistance.Hepatic steatosis is regarded as a benign stage of NAFLD but may progress to NASH in a subgroup of patients.Besides liver biopsy no diagnostic tools to identify patients with NASH are available,and no effective treatment has been established.Visceral obesity is a main risk factor for NAFLD and inappropriate storage of triglycerides in adipocytes and higher concentrations of free fatty acids may add to increased hepatic lipid storage,insulin resistance,and progressive liver damage.Most of the adipose tissue-derived proteins are elevated in obesity and may contribute to systemic inflammation and liver damage.Adiponectin is highly abundant in human serum but its levels are reduced in obesity and are even lower in patients with hepatic steatosis or NASH.Adiponectin antagonizes excess lipid storage in the liver and protects from inflammation and fibrosis.This review aims to give a short survey on NAFLD and the hepatoprotective effects of adiponectin.展开更多
Background Adipose tissue-derived stromal cells (ADS Cs) can be greatly expanded in vitro, and induced to differentiate into multiple mesenchymal cell types, including osteogenic, chondrogenic, myogenic, and adipogeni...Background Adipose tissue-derived stromal cells (ADS Cs) can be greatly expanded in vitro, and induced to differentiate into multiple mesenchymal cell types, including osteogenic, chondrogenic, myogenic, and adipogenic cells. This study was designed to investigate the possibility of ADSCs differentiating into neurons.Methods Adipose tissue from rats was digested with collagenase, and adherent stromal cells were cultured. A medium containing a low concentration of fetal bovine serum was adopted to induce the cells to differentiate. ADSCs were identified by immunocytochemistry, and semi-quantitative RT-PCR was applied to detect mRNA expression of neurofilament 1 (NF1), nestin, and neuron-specific enolase (NSE).Results Nestin-positive cells were found occasionally among ADSCs. ADSCs were found to express NSE mRNA and nestin mRNA, but not NF1 mRNA. ADSCs could differentiate into neuron-like cells in a medium composed of a low concentration of fetal bovine serum, and these differentiated cells displayed complicated neuron-like morphologies.Conclusions The data support the hypothesis that adipose tissue contains stem cells capable of differentiating into neurons. These stem cells can overcome their mesenchymal commitment, and may represent an alternative autologous stem cell source for CNS cell transplantation.展开更多
AIM： To investigate and compare the hepatogenic transdifferentiation of adipose tissue-derived stem cells （ADSC） and bone marrow-derived mesenchymal stem cells （BMSC） in vitro. Transdifferentiation of BMSC into h...AIM： To investigate and compare the hepatogenic transdifferentiation of adipose tissue-derived stem cells （ADSC） and bone marrow-derived mesenchymal stem cells （BMSC） in vitro. Transdifferentiation of BMSC into hepatic cells in vivo has been described. Adipose tissue represents an accessible source of ADSC, with similar characteristics to BMSC. METHODS： BMSCs were obtained from patients undergoing total hip arthroplasty and ADSC from human adipose tissue obtained from lipectomy. Cells were grown in medium containing 15% human serum. Cultures were serum deprived for 2 d before cultivating under similar pro-hepatogenic conditions to those of liver development using a 2-step protocol with sequential addition of growth factors, cytokines and hormones. Hepatic differentiation was RT-PCR-assessed and liver-marker genes were immunohistochemically analysed.RESULTS： BMSC and ADSC exhibited a fibroblastic morphology that changed to a polygonal shape when cells differentiated. Expression of stem cell marker Thyl decreased in differentiated ADSC and BMSC. However, the expression of the hepatic markers, albumin and CYPs increased to a similar extent in differentiated BMSC and ADSC. Hepatic gene activation could be attributed to increased liver-enriched transcription factors （C/EBPβ and HNF4α）, as demonstrated by adenoviral expression vectors.CONCLUSION： Mesenchymal stem cells can be induced to hepatogenic transdifferentiation in vitro. ADSCs have a similar hepatogenic differentiation potential to BMSC, but a longer culture period and higher proliferation capacity. Therefore, adipose tissue may be an ideal source of large amounts of autologous stem cells, and may become an alternative for hepatocyte regeneration, liver cell transplantation or preclinical drug testing.展开更多
Diabetes mellitus is increasing at an alarming rate and has become a global challenge.Insulin resistance intarget tissues and a relative deficiency of insulin secretion from pancreatic β-cells are the major features ...Diabetes mellitus is increasing at an alarming rate and has become a global challenge.Insulin resistance intarget tissues and a relative deficiency of insulin secretion from pancreatic β-cells are the major features of type 2 diabetes(T2D).Chronic low-grade inflammation in T2 D has given an impetus to the field of immuno-metabolism linking inflammation to insulin resistance and β-cell dysfunction.Many factors advocate a causal link between metabolic stress and inflammation.Numerous cellular factors trigger inflammatory signalling cascades,and as a result T2 D is at the moment considered an inflammatory disorder triggered by disordered metabolism.Cellular mechanisms like activation of Tolllike receptors,Endoplasmic Reticulum stress,and inflammasome activation are related to the nutrient excess linking pathogenesis and progression of T2 D with inflammation.This paper aims to systematically review the metabolic profile and role of various inflammatory pathways in T2 D by capturing relevant evidence from various sources.The perspectives include suggestions for the development of therapies involving the shift from metabolic stress to homeostasis that would favour insulin sensitivity and survival of pancreatic β-cells in T2 D.展开更多
Leptin is the protein product encoded by the obese (ob)gene. It is a circulating hormone produced primarily by the adipose tissue. ob/ob mice with mutations of the gene encoding leptin become morbidly obese, infertile...Leptin is the protein product encoded by the obese (ob)gene. It is a circulating hormone produced primarily by the adipose tissue. ob/ob mice with mutations of the gene encoding leptin become morbidly obese, infertile, hyperphagic, hypothermic,and diabetic. Since the cloning of leptin in 1994, our knowledge in body weight regulation and the role played by leptin has increased substantially. We now know that leptin signals through its receptor, OB-R, which is a member of the cytokine receptor superfamily. Leptin serves as an adiposity signal to inform the brain the adipose tissue mass in a negative feedback loop regulating food intake and energy expenditure. Leptin also plays important roles in angiogenesis, immune function, fertility and bone formation. Humans with mutations in the gene encoding leptin are also morbidly obese and respond to leptin treatment,demonstrating that enhancing or inhibiting leptin’s activities in vivo may have potential therapeutic benefits.展开更多
With technological advances in basic research,the intricate mechanism of secondary delayed spinal cord injury(SCI)continues to unravel at a rapid pace.However,despite our deeper understanding of the molecular changes ...With technological advances in basic research,the intricate mechanism of secondary delayed spinal cord injury(SCI)continues to unravel at a rapid pace.However,despite our deeper understanding of the molecular changes occurring after initial insult to the spinal cord,the cure for paralysis remains elusive.Current treatment of SCI is limited to early administration of high dose steroids to mitigate the harmful effect of cord edema that occurs after SCI and to reduce the cascade of secondary delayed SCI.R ecent evident-based clinical studies have cast doubt on the clinical benefit of steroids in SCI and intense focus on stem cell-based therapy has yielded some encouraging results.An array of mesenchymal stem cells(MSCs)from various sources with novel and promising strategies are being developed to improve function after SCI.In this review,we briefly discuss the pathophysiology of spinal cord injuries and characteristics and the potential sources of MSCs that can be used in the treatment of SCI.We will discuss the progress of MSCs application in research,focusing on the neuroprotective properties of MSCs.Finally,we will discuss the results from preclinical and clinical trials involving stem cell-based therapy in SCI.展开更多
In adults, adipose tissue is abundant and can be easily sampled using liposuction. Largely involved in obesity and associated metabolic disorders, it is now described as a reservoir of immature stromal cells. These ce...In adults, adipose tissue is abundant and can be easily sampled using liposuction. Largely involved in obesity and associated metabolic disorders, it is now described as a reservoir of immature stromal cells. These cells, called adipose-derived stromal cells (ADSCs) must be distinguished from the crude stromal vascular fraction (SVF) obtained after digestion of adipose tissue. ADSCs share many features with mesenchymal stem cells derived from bone marrow, including paracrine activity, but they also display some specific features, including a greater angiogenic potential. Their angiogenic properties as well as their paracrine activity suggest a putative tumor-promoting role for ADSCs although contradictory data have been published on this issue. Both SVF cells and ADSCs are currently being investigated in clinical trials in several fields (chronic inflammation, ischemic diseases, etc. ). Apart from a phase Ⅲ trial on the treatment of fistula,most of these are in phaseⅠand use autologous cells. In the near future, the end results of these trials should provide a great deal of data on the safety of ADSC use.展开更多
Intrahepatic fat deposition has been demonstrated in patients with nonalcoholic fatty liver disease(NAFLD). Genetic and environmental factors are important for the development of NAFLD. Diseases such as obesity, diabe...Intrahepatic fat deposition has been demonstrated in patients with nonalcoholic fatty liver disease(NAFLD). Genetic and environmental factors are important for the development of NAFLD. Diseases such as obesity, diabetes, and hypertension have been found to be closely associated with the incidence of NAFLD. Evi-dence suggests that obesity and insulin resistance are the major factors that contribute to the development of NAFLD. In comparing the factors that contribute to the buildup of excess calories in obesity, an imbalance of energy homeostasis can be considered as the basis. Among the peripheral signals that are generated to regulate the uptake of food, signals from adipose tissue are of major relevance and involve the maintenance of energy homeostasis through processes such as lipo-genesis, lipolysis, and oxidation of fatty acids. Advances in research on adipose tissue suggest an integral role played by adipokines in NAFLD. Cytokines secreted by adipocytes, such as tumor necrosis factor-α, transform-ing growth factor-β, and interleukin-6, are implicated in NAFLD. Other adipokines, such as leptin and adiponectin and, to a lesser extent, resistin and retinol binding protein-4 are also involved. Leptin and adiponectin can augment the oxidation of fatty acid in liver by activating the nuclear receptor super-family of transcription fac-tors, namely peroxisome proliferator-activated receptor(PPAR)-α. Recent studies have proposed downregula-tion of PPAR-α in cases of hepatic steatosis. This re-view discusses the role of adipokines and PPARs with regard to hepatic energy metabolism and progression of NAFLD.展开更多
Background Human adipose tissue-derived stromal cells （hADSCs） can be induced to differentiate along an osteoblastic lineage under stimulation of dexamethasone （DEX）. Recent studies, however, have questioned the e...Background Human adipose tissue-derived stromal cells （hADSCs） can be induced to differentiate along an osteoblastic lineage under stimulation of dexamethasone （DEX）. Recent studies, however, have questioned the efficacy of glucocorticoids such as DEX in mediating the osteogenesis process of skeletal progenitor cells and processed lipoaspirate cells. Is it possible to find a substitute for DEX？ Therefore, this study was designed to investigate osteogenic capacity and regulating mechanisms for osteoblastic differentiation of hADSCs by comparing osteogenic media （OM） containing either 1, 25-dihydroxyvitamin D3 （VD） or DEX and determine if VD was an ideal substitute for DEX as an induction agent for the osteogenesis of hADSCs. Methods Osteogenic differentiation of hADSCs was induced by osteogenic medium （OM） containing either 10 nmol/L VD or 100 nmol/L DEX. Differentiation of hADSCs into osteoblastic lineage was identified by alkaline phosphatase （ALP） staining, von Kossa staining, and reverse transcription-polymerase chain reaction assays for mRNA expression of osteogenesis-related genes such as type Ⅰ collagen （COL Ⅰ）, bone sialoprotein （BSP）, osteocalcin （OC）, bone morphogenetic protein （BMP）-2, BMP-4, BMP-6, BMP-7, runt-related transcription factor 2/core binding factor α1 （Runx2/Cbfal）, osterix （Osx）, and LIM mineralization protein- 1 （LMP- 1）. Results von Kossa staining revealed that the differentiated cells induced by both VD and DEX were mineralized in vitro. They also expressed osteoblast-related markers, such as ALP, COL Ⅰ, BSP, and OC. Runx2/Cbfal, Osx, BMP-6, and LMP-1 were upregulated during VD and DEX-induced hADSC osteoblastic differentiation, but BMP-4, BMP-7 were not. BMP-2 was only expressed in VD-induced differentiated cells. Conclusions VD or DEX-induced hADSCs differentiate toward the osteoblastic lineage in vitro. Runx2/Cbfal, Osx, BMP-2, BMP-6, and LMP-1 are involved in regulating osteoblastic differentiation of hADSCs, but BMP-4, BM展开更多
Pigs lack functional uncoupling protein 1 （UCP1） making them susceptible to cold. Nevertheless, several pig breeds are known to be cold resistant. The molecular mechanism（s） enabling such adaptation are currently ...Pigs lack functional uncoupling protein 1 （UCP1） making them susceptible to cold. Nevertheless, several pig breeds are known to be cold resistant. The molecular mechanism（s） enabling such adaptation are currently unknown. Here, we show that this resist- ance is not dependent on shivering, but rather depends on UCP3 and white adipose tissue （WAT） browning. In two cold-resistant breeds （Tibetan and Min）, but not a cold-sensitive breed （Bama）, WAT browning was induced after cold exposure. Beige adipo- cytes from Tibetan pigs exhibited greater oxidative capacity than those from Bama pigs. Notably, UCP3 expression was signifi- cantly increased only in cold-resistant breeds, and knockdown of UCP3 expression in Tibetan adipocytes phenocopied Bama adipocytes in culture. Moreover, the eight dominant pig breeds found across China can be classified into cold-sensitive and cold- resistant breeds based on the UCP3 cDNA sequence. This study indicates that UCP3 has contributed to the evolution of cold resistance in the pig and overturns the orthodoxy that UCP1 is the only thermogenic uncoupling protein.展开更多
Obesity is increasing in an alarming rate worldwide, which causes higher risks of some diseases, such as type 2 diabetes, cardiovascular diseases, and cancer. Current therapeutic approaches,either pancreatic lipase in...Obesity is increasing in an alarming rate worldwide, which causes higher risks of some diseases, such as type 2 diabetes, cardiovascular diseases, and cancer. Current therapeutic approaches,either pancreatic lipase inhibitors or appetite suppressors, are generally of limited effectiveness. Brown adipose tissue(BAT) and beige cells dissipate fatty acids as heat to maintain body temperature, termed non-shivering thermogenesis; the activity and mass of BAT and beige cells are negatively correlated with overweight and obesity. The existence of BAT and beige cells in human adults provides an effective weight reduction therapy, a process likely to be amenable to pharmacological intervention. Herein, we combed through the physiology of thermogenesis and the role of BAT and beige cells in combating with obesity. We summarized the thermogenic regulators identified in the past decades, targeting G proteincoupled receptors, transient receptor potential channels, nuclear receptors and miscellaneous pathways.Advances in clinical trials were also presented. The main purpose of this review is to provide a comprehensive and up-to-date knowledge from the biological importance of thermogenesis in energy homeostasis to the representative thermogenic regulators for treating obesity. Thermogenic regulatorsmight have a large potential for further investigations to be developed as lead compounds in fighting obesity.展开更多
Background Adipose-derived stem cells （ADSCs） are capable of differentiating into cardiomyogenic and endothelial cells in vitro. We tested the hypothesis that transplantation of ADSCs into myocardial scar may regene...Background Adipose-derived stem cells （ADSCs） are capable of differentiating into cardiomyogenic and endothelial cells in vitro. We tested the hypothesis that transplantation of ADSCs into myocardial scar may regenerate infracted myocardium and restore cardiac function. Methods ADSCs were isolated from the fatty tissue of New Zealand white rabbits and cultured in Iscove＇s modified dulbecco＇s medium. Three weeks after ligation of left anterior descending coronary artery of rabbits, either a graft of untreated ADSCs （UASCs, n=14）, 5-azacytidine-pretreated ADSCs （AASCs, n=13）, or phosphate buffer saline （n=13） were injected into the infarct region. Transmural scar size, cardiac function, and immunohistochemistry were performed 5 weeks after cell transplantation. Results ADSCs in culture demonstrated a fibroblast-like appearance and expressed CD29, CD44 and CD105. Five weeks after cell transplantation, transmural scar size in AASC-implanted hearts was smaller than that of the other hearts. Many ADSCs were differentiated into cardiomyocytes. The AASCs in the prescar appeared more myotube-like. AASCs in the middle of the scar and UASCs, in contrast, were poorly differentiated. Some ADSCs were differentiated into endothelial cells and participate in vessel-like structures formation. All the ADSC-implanted hearts had a greater capillary density in the infarct region than did the control hearts. Statistical analyses revealed significant improvement in left ventricular ejection fraction, myocardial performance index, end-diastolic pressure, and peak ＋dP/dt, in two groups of ADSC-implanted hearts relative to the control hearts. AASC-implanted hearts had higher peak -dP/dt values than did control, higher ejection fraction and peak ＋dP/dt values than did UASC-implanted hearts. Conclusions ADSCs transplanted into the myocardial scar tissue formed cardiac islands and vessel-like structures, induced angiogenesis and improved cardiac function. 5-Azacytidine pretreatment before implantation is desirable for展开更多
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different no...Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients.展开更多
文摘Nonalcoholic fatty liver disease （NAFLD） is an increasingly recognized cause of liver-related morbidity and mortality. It can develop secondary to numerous causes but a great majority of NAFLD cases occur in patients who are obese or present with other components of metabolic syndrome （hypertension, dyslipidemia, diabetes）. This is called primary NAFLD and insulin resistance plays a key role in its pathogenesis. Obesity is characterized by expanded adipose tissue, which is under a state of chronic inflammation. This disturbs the normal storage and endocrine functions of adipose tissue. In obesity, the secretome （adipokines, oytokines, free fatty acids and other lipid moieties） of fatty tissue is amplified, which through its autocrine, paracrine actions in fat tissue and systemic effects especially in the liver leads to an altered metabolic state with insulin resistance （IR）. IR leads to hyperglycemia and reactive hyperinsulinemia, which stimulates lipid-accumulating processes and impairs hepatic lipid metabolism. IR enhances free fatty acid delivery to liver from the adipose tissue storage due to uninhibited lipolysis. These changes result in hepatic abnormal fat accumulation, which may initiate the hepatic IR and further aggravate the altered metabolic state of whole body. Hepatic steatosis can also be explained by the fact that there is enhanced dietary fat delivery and physical inactivity. IR and NAFLD are also seen in various lipodystrophic states in contrary to popular belief that these problems only occur due to excessive adiposity in obesity. Hence, altered physiology of adipose tissue is central to development of IR, metabolic syndrome and NAFLD.
文摘BACKGROUND: Acute rejection after liver transplantation is usually treated with large doses of immunosuppressants with severe toxic and side-effects, so it is imperative to find a safe and effective method for preventing and treating rejection. This study was designed to confirm the immunomodulatory effects of rat mesenchymal stem cells (MSCs) in vitro and investigate the tolerogenic features in a rat model of allogeneic liver transplantation. METHODS: MSCs were isolated from adipose tissue of Sprague-Dawley (SD) rats and cultured. In vitro, MSCs were added into a mixed lymphocyte culture (MLC) system to study the inhibitory effects of MSCs on the proliferation of T lymphocytes in Wistar rats. By using SD and Wistar rats as liver donors and recipients, an orthotopic liver transplantation model was established and the rats were divided into a MSC-treated group and a blank control group. On postoperative day 7, all rats were sacrificed, and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), interleukin-2 (IL-2) and interleukin-10 (IL-10) were measured. The pathological changes of liver tissue and apoptosis of hepatocytes were also assessed. RESULTS: In in vitro MLC, T lymphocyte proliferation in Wistar rats was significantly inhibited by 48.44%. In the MSC-treated group, the levels of ALT, AST, TBIL, IL-2 and IL-10 were 134.2 +/- 45.0 U/L, 162.5 +/- 30.5 U/L, 30.6 +/- 5.4 mu mol/L, 187.35 +/- 18.26 mu g/L and 193.95 +/- 37.62 mu g/L, and those in the blank control group were 355.6 +/- 54.3 U/L, 296.4 +/- 71.2 U/L, 145.7 +/- 28.6 +/- mol/L, 295.73 +/- 57.15 mu g/L and 75.12 +/- 11.23 mu g/L, respectively, with statistically significant differences (P<0.05). Pathological examination revealed that the rejection in the MSC-treated group was clearly alleviated compared with that in the blank control group. TUNEL indicated that the apoptosis of hepatocytes in the MSC-treated group was milder than that in the blank control group (P<0.05). CONCLUSION: Adipose-derived MSC
基金Supported by The Faculty of Medicine of the University of Regensburg (ReForM C)The Deutsche Forschungsgemein-schaft
文摘Non-alcoholic fatty liver disease (NAFLD) comprising hepatic steatosis,non-alcoholic steatohepatitis (NASH),and progressive liver fibrosis is considered the most common liver disease in western countries.Fatty liver is more prevalent in overweight than normal-weight people and liver fat positively correlates with hepatic insulin resistance.Hepatic steatosis is regarded as a benign stage of NAFLD but may progress to NASH in a subgroup of patients.Besides liver biopsy no diagnostic tools to identify patients with NASH are available,and no effective treatment has been established.Visceral obesity is a main risk factor for NAFLD and inappropriate storage of triglycerides in adipocytes and higher concentrations of free fatty acids may add to increased hepatic lipid storage,insulin resistance,and progressive liver damage.Most of the adipose tissue-derived proteins are elevated in obesity and may contribute to systemic inflammation and liver damage.Adiponectin is highly abundant in human serum but its levels are reduced in obesity and are even lower in patients with hepatic steatosis or NASH.Adiponectin antagonizes excess lipid storage in the liver and protects from inflammation and fibrosis.This review aims to give a short survey on NAFLD and the hepatoprotective effects of adiponectin.
文摘Background Adipose tissue-derived stromal cells (ADS Cs) can be greatly expanded in vitro, and induced to differentiate into multiple mesenchymal cell types, including osteogenic, chondrogenic, myogenic, and adipogenic cells. This study was designed to investigate the possibility of ADSCs differentiating into neurons.Methods Adipose tissue from rats was digested with collagenase, and adherent stromal cells were cultured. A medium containing a low concentration of fetal bovine serum was adopted to induce the cells to differentiate. ADSCs were identified by immunocytochemistry, and semi-quantitative RT-PCR was applied to detect mRNA expression of neurofilament 1 (NF1), nestin, and neuron-specific enolase (NSE).Results Nestin-positive cells were found occasionally among ADSCs. ADSCs were found to express NSE mRNA and nestin mRNA, but not NF1 mRNA. ADSCs could differentiate into neuron-like cells in a medium composed of a low concentration of fetal bovine serum, and these differentiated cells displayed complicated neuron-like morphologies.Conclusions The data support the hypothesis that adipose tissue contains stem cells capable of differentiating into neurons. These stem cells can overcome their mesenchymal commitment, and may represent an alternative autologous stem cell source for CNS cell transplantation.
基金Supported by the ALIVE Foundation, the FIS from Instituto de Salud Carlos III, Spain, No. 03/0339, and the European Commission, No. LSHB-CT-2004-504761
文摘AIM： To investigate and compare the hepatogenic transdifferentiation of adipose tissue-derived stem cells （ADSC） and bone marrow-derived mesenchymal stem cells （BMSC） in vitro. Transdifferentiation of BMSC into hepatic cells in vivo has been described. Adipose tissue represents an accessible source of ADSC, with similar characteristics to BMSC. METHODS： BMSCs were obtained from patients undergoing total hip arthroplasty and ADSC from human adipose tissue obtained from lipectomy. Cells were grown in medium containing 15% human serum. Cultures were serum deprived for 2 d before cultivating under similar pro-hepatogenic conditions to those of liver development using a 2-step protocol with sequential addition of growth factors, cytokines and hormones. Hepatic differentiation was RT-PCR-assessed and liver-marker genes were immunohistochemically analysed.RESULTS： BMSC and ADSC exhibited a fibroblastic morphology that changed to a polygonal shape when cells differentiated. Expression of stem cell marker Thyl decreased in differentiated ADSC and BMSC. However, the expression of the hepatic markers, albumin and CYPs increased to a similar extent in differentiated BMSC and ADSC. Hepatic gene activation could be attributed to increased liver-enriched transcription factors （C/EBPβ and HNF4α）, as demonstrated by adenoviral expression vectors.CONCLUSION： Mesenchymal stem cells can be induced to hepatogenic transdifferentiation in vitro. ADSCs have a similar hepatogenic differentiation potential to BMSC, but a longer culture period and higher proliferation capacity. Therefore, adipose tissue may be an ideal source of large amounts of autologous stem cells, and may become an alternative for hepatocyte regeneration, liver cell transplantation or preclinical drug testing.
基金Supported by Department of Science and Technology,Government of India to Iqra Hameed,No.Wos-A LS 509/2012
文摘Diabetes mellitus is increasing at an alarming rate and has become a global challenge.Insulin resistance intarget tissues and a relative deficiency of insulin secretion from pancreatic β-cells are the major features of type 2 diabetes(T2D).Chronic low-grade inflammation in T2 D has given an impetus to the field of immuno-metabolism linking inflammation to insulin resistance and β-cell dysfunction.Many factors advocate a causal link between metabolic stress and inflammation.Numerous cellular factors trigger inflammatory signalling cascades,and as a result T2 D is at the moment considered an inflammatory disorder triggered by disordered metabolism.Cellular mechanisms like activation of Tolllike receptors,Endoplasmic Reticulum stress,and inflammasome activation are related to the nutrient excess linking pathogenesis and progression of T2 D with inflammation.This paper aims to systematically review the metabolic profile and role of various inflammatory pathways in T2 D by capturing relevant evidence from various sources.The perspectives include suggestions for the development of therapies involving the shift from metabolic stress to homeostasis that would favour insulin sensitivity and survival of pancreatic β-cells in T2 D.
文摘Leptin is the protein product encoded by the obese (ob)gene. It is a circulating hormone produced primarily by the adipose tissue. ob/ob mice with mutations of the gene encoding leptin become morbidly obese, infertile, hyperphagic, hypothermic,and diabetic. Since the cloning of leptin in 1994, our knowledge in body weight regulation and the role played by leptin has increased substantially. We now know that leptin signals through its receptor, OB-R, which is a member of the cytokine receptor superfamily. Leptin serves as an adiposity signal to inform the brain the adipose tissue mass in a negative feedback loop regulating food intake and energy expenditure. Leptin also plays important roles in angiogenesis, immune function, fertility and bone formation. Humans with mutations in the gene encoding leptin are also morbidly obese and respond to leptin treatment,demonstrating that enhancing or inhibiting leptin’s activities in vivo may have potential therapeutic benefits.
基金Supported by A grant from Illinois Neurological Institute to DHD
文摘With technological advances in basic research,the intricate mechanism of secondary delayed spinal cord injury(SCI)continues to unravel at a rapid pace.However,despite our deeper understanding of the molecular changes occurring after initial insult to the spinal cord,the cure for paralysis remains elusive.Current treatment of SCI is limited to early administration of high dose steroids to mitigate the harmful effect of cord edema that occurs after SCI and to reduce the cascade of secondary delayed SCI.R ecent evident-based clinical studies have cast doubt on the clinical benefit of steroids in SCI and intense focus on stem cell-based therapy has yielded some encouraging results.An array of mesenchymal stem cells(MSCs)from various sources with novel and promising strategies are being developed to improve function after SCI.In this review,we briefly discuss the pathophysiology of spinal cord injuries and characteristics and the potential sources of MSCs that can be used in the treatment of SCI.We will discuss the progress of MSCs application in research,focusing on the neuroprotective properties of MSCs.Finally,we will discuss the results from preclinical and clinical trials involving stem cell-based therapy in SCI.
文摘In adults, adipose tissue is abundant and can be easily sampled using liposuction. Largely involved in obesity and associated metabolic disorders, it is now described as a reservoir of immature stromal cells. These cells, called adipose-derived stromal cells (ADSCs) must be distinguished from the crude stromal vascular fraction (SVF) obtained after digestion of adipose tissue. ADSCs share many features with mesenchymal stem cells derived from bone marrow, including paracrine activity, but they also display some specific features, including a greater angiogenic potential. Their angiogenic properties as well as their paracrine activity suggest a putative tumor-promoting role for ADSCs although contradictory data have been published on this issue. Both SVF cells and ADSCs are currently being investigated in clinical trials in several fields (chronic inflammation, ischemic diseases, etc. ). Apart from a phase Ⅲ trial on the treatment of fistula,most of these are in phaseⅠand use autologous cells. In the near future, the end results of these trials should provide a great deal of data on the safety of ADSC use.
文摘Intrahepatic fat deposition has been demonstrated in patients with nonalcoholic fatty liver disease(NAFLD). Genetic and environmental factors are important for the development of NAFLD. Diseases such as obesity, diabetes, and hypertension have been found to be closely associated with the incidence of NAFLD. Evi-dence suggests that obesity and insulin resistance are the major factors that contribute to the development of NAFLD. In comparing the factors that contribute to the buildup of excess calories in obesity, an imbalance of energy homeostasis can be considered as the basis. Among the peripheral signals that are generated to regulate the uptake of food, signals from adipose tissue are of major relevance and involve the maintenance of energy homeostasis through processes such as lipo-genesis, lipolysis, and oxidation of fatty acids. Advances in research on adipose tissue suggest an integral role played by adipokines in NAFLD. Cytokines secreted by adipocytes, such as tumor necrosis factor-α, transform-ing growth factor-β, and interleukin-6, are implicated in NAFLD. Other adipokines, such as leptin and adiponectin and, to a lesser extent, resistin and retinol binding protein-4 are also involved. Leptin and adiponectin can augment the oxidation of fatty acid in liver by activating the nuclear receptor super-family of transcription fac-tors, namely peroxisome proliferator-activated receptor(PPAR)-α. Recent studies have proposed downregula-tion of PPAR-α in cases of hepatic steatosis. This re-view discusses the role of adipokines and PPARs with regard to hepatic energy metabolism and progression of NAFLD.
基金This study was supported by a grant from the National Natural Science Foundation of China (No. 30200319).
文摘Background Human adipose tissue-derived stromal cells （hADSCs） can be induced to differentiate along an osteoblastic lineage under stimulation of dexamethasone （DEX）. Recent studies, however, have questioned the efficacy of glucocorticoids such as DEX in mediating the osteogenesis process of skeletal progenitor cells and processed lipoaspirate cells. Is it possible to find a substitute for DEX？ Therefore, this study was designed to investigate osteogenic capacity and regulating mechanisms for osteoblastic differentiation of hADSCs by comparing osteogenic media （OM） containing either 1, 25-dihydroxyvitamin D3 （VD） or DEX and determine if VD was an ideal substitute for DEX as an induction agent for the osteogenesis of hADSCs. Methods Osteogenic differentiation of hADSCs was induced by osteogenic medium （OM） containing either 10 nmol/L VD or 100 nmol/L DEX. Differentiation of hADSCs into osteoblastic lineage was identified by alkaline phosphatase （ALP） staining, von Kossa staining, and reverse transcription-polymerase chain reaction assays for mRNA expression of osteogenesis-related genes such as type Ⅰ collagen （COL Ⅰ）, bone sialoprotein （BSP）, osteocalcin （OC）, bone morphogenetic protein （BMP）-2, BMP-4, BMP-6, BMP-7, runt-related transcription factor 2/core binding factor α1 （Runx2/Cbfal）, osterix （Osx）, and LIM mineralization protein- 1 （LMP- 1）. Results von Kossa staining revealed that the differentiated cells induced by both VD and DEX were mineralized in vitro. They also expressed osteoblast-related markers, such as ALP, COL Ⅰ, BSP, and OC. Runx2/Cbfal, Osx, BMP-6, and LMP-1 were upregulated during VD and DEX-induced hADSC osteoblastic differentiation, but BMP-4, BMP-7 were not. BMP-2 was only expressed in VD-induced differentiated cells. Conclusions VD or DEX-induced hADSCs differentiate toward the osteoblastic lineage in vitro. Runx2/Cbfal, Osx, BMP-2, BMP-6, and LMP-1 are involved in regulating osteoblastic differentiation of hADSCs, but BMP-4, BM
文摘Pigs lack functional uncoupling protein 1 （UCP1） making them susceptible to cold. Nevertheless, several pig breeds are known to be cold resistant. The molecular mechanism（s） enabling such adaptation are currently unknown. Here, we show that this resist- ance is not dependent on shivering, but rather depends on UCP3 and white adipose tissue （WAT） browning. In two cold-resistant breeds （Tibetan and Min）, but not a cold-sensitive breed （Bama）, WAT browning was induced after cold exposure. Beige adipo- cytes from Tibetan pigs exhibited greater oxidative capacity than those from Bama pigs. Notably, UCP3 expression was signifi- cantly increased only in cold-resistant breeds, and knockdown of UCP3 expression in Tibetan adipocytes phenocopied Bama adipocytes in culture. Moreover, the eight dominant pig breeds found across China can be classified into cold-sensitive and cold- resistant breeds based on the UCP3 cDNA sequence. This study indicates that UCP3 has contributed to the evolution of cold resistance in the pig and overturns the orthodoxy that UCP1 is the only thermogenic uncoupling protein.
基金Financial support by Science and Technology Development Fund,Macao SAR,China(FDCT 102/2017/A)the Research Fund of University of Macao,China(MYRG2017-00109-ICMS)
文摘Obesity is increasing in an alarming rate worldwide, which causes higher risks of some diseases, such as type 2 diabetes, cardiovascular diseases, and cancer. Current therapeutic approaches,either pancreatic lipase inhibitors or appetite suppressors, are generally of limited effectiveness. Brown adipose tissue(BAT) and beige cells dissipate fatty acids as heat to maintain body temperature, termed non-shivering thermogenesis; the activity and mass of BAT and beige cells are negatively correlated with overweight and obesity. The existence of BAT and beige cells in human adults provides an effective weight reduction therapy, a process likely to be amenable to pharmacological intervention. Herein, we combed through the physiology of thermogenesis and the role of BAT and beige cells in combating with obesity. We summarized the thermogenic regulators identified in the past decades, targeting G proteincoupled receptors, transient receptor potential channels, nuclear receptors and miscellaneous pathways.Advances in clinical trials were also presented. The main purpose of this review is to provide a comprehensive and up-to-date knowledge from the biological importance of thermogenesis in energy homeostasis to the representative thermogenic regulators for treating obesity. Thermogenic regulatorsmight have a large potential for further investigations to be developed as lead compounds in fighting obesity.
文摘Background Adipose-derived stem cells （ADSCs） are capable of differentiating into cardiomyogenic and endothelial cells in vitro. We tested the hypothesis that transplantation of ADSCs into myocardial scar may regenerate infracted myocardium and restore cardiac function. Methods ADSCs were isolated from the fatty tissue of New Zealand white rabbits and cultured in Iscove＇s modified dulbecco＇s medium. Three weeks after ligation of left anterior descending coronary artery of rabbits, either a graft of untreated ADSCs （UASCs, n=14）, 5-azacytidine-pretreated ADSCs （AASCs, n=13）, or phosphate buffer saline （n=13） were injected into the infarct region. Transmural scar size, cardiac function, and immunohistochemistry were performed 5 weeks after cell transplantation. Results ADSCs in culture demonstrated a fibroblast-like appearance and expressed CD29, CD44 and CD105. Five weeks after cell transplantation, transmural scar size in AASC-implanted hearts was smaller than that of the other hearts. Many ADSCs were differentiated into cardiomyocytes. The AASCs in the prescar appeared more myotube-like. AASCs in the middle of the scar and UASCs, in contrast, were poorly differentiated. Some ADSCs were differentiated into endothelial cells and participate in vessel-like structures formation. All the ADSC-implanted hearts had a greater capillary density in the infarct region than did the control hearts. Statistical analyses revealed significant improvement in left ventricular ejection fraction, myocardial performance index, end-diastolic pressure, and peak ＋dP/dt, in two groups of ADSC-implanted hearts relative to the control hearts. AASC-implanted hearts had higher peak -dP/dt values than did control, higher ejection fraction and peak ＋dP/dt values than did UASC-implanted hearts. Conclusions ADSCs transplanted into the myocardial scar tissue formed cardiac islands and vessel-like structures, induced angiogenesis and improved cardiac function. 5-Azacytidine pretreatment before implantation is desirable for
文摘Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients.
