Abstract 402: Human CD271-positive Adipose Derived Stem Cells are the Angiogenic Subset Decreased by Donor Insulin Resistance

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Oto Inoue ◽  
Soichiro Usui ◽  
Kosei Yamaguchi ◽  
Yusuke Takeda ◽  
Chiaki Goten ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Stem Cells ◽  
Adipose Tissue ◽  
Cell Therapy ◽  
Capillary Density ◽  
Adipose Derived Stem Cells ◽  
Knock Out ◽  
Healthy Donors ◽  
Knock Out Mice

Introduction: Type 2 diabetes mellitus (T2DM) is an important risk factor for cardiovascular diseases (CVDs). Recently, cell therapy using adipose-derived stem cells (ADSCs) has emerged as an attractive therapy for severe CVDs because of their angiogenic potentials. However, whether and how T2DM would impair human ADSC angiogenic capacity is still uncertain. We previously reported that CD31 - CD34 + CD271 + ADSCs (CD271 + ADSCs) were specifically decreased in adipose tissue of T2DM patients. Therefore, we aimed to investigate the angiogenic capacity of CD271 + ADSCs. Furthermore, we evaluate which patients’ parameters regard as T2DM would decrease the amount of CD271 + ADSCs. Methods and Results: Human CD45 - CD34 + CD31 - ADSCs were obtained from subcutaneous adipose tissue of healthy donors, separated into CD271 + and CD271 - subsets by FACS, and cultured. Both subsets of ADSCs were assessed gene expression profile by microarray. Microarray analysis and validation PCR elucidated that PI3K/Akt/mTOR pathway was significantly up-regulated in CD271 + ADSCs compared to in CD271 - ADSCs. ( p < 0.05). Then, we compared in vivo angiogenic capacity in xenograft experiments of nude mice subjected to hindlimb ischemia. Angiogenesis was evaluated histologically using perfused lectin (capillary density) at day 14. Cell therapy using CD271 + ADSCs demonstrated about 3-fold more lectin + capillaries compared to CD271 - ADSCs or PBS injection ( p < 0.005, n = 5 / group). Next, we established cultured ADSCs obtained from CD271 knock-out mice (KO-ADSCs) and compared their angiogenic capacity with those from WT mice. Consistently, KO-ADSCs demonstrated impaired in vivo angiogenic capacity ( p < 0.005, n = 5 / group). Finally, we collected 23 samples of adipose tissue obtained from CVD patients and evaluated the frequency of CD271 + ADSCs in CD45 - CD34 + CD31 - ADSCs. Among studied parameters, HOMA-IR, an index of insulin resistance, was negatively correlated with the frequency of CD271+ ADSCs ( r = -0.64, p < 0.005). Conclusions: Human CD271 + ADSCs demonstrated enhanced in vivo angiogenic capacity with higher mTOR expression. Donor insulin resistance might decrease this regenerative subset of ADSCs. These findings would be critical for development and improvement of ADSC therapy.

scholarly journals Comparative analysis of mouse bone marrow and adipose tissue mesenchymal stem cells for critical limb ischemia cell therapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pegah Nammian ◽  
Seyedeh-Leili Asadi-Yousefabad ◽  
Sajad Daneshi ◽  
Mohammad Hasan Sheikhha ◽  
Seyed Mohammad Bagher Tabei ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Cell Therapy ◽  
Femoral Artery ◽  
Critical Limb Ischemia ◽  
Limb Ischemia

Abstract Introduction Critical limb ischemia (CLI) is the most advanced form of peripheral arterial disease (PAD) characterized by ischemic rest pain and non-healing ulcers. Currently, the standard therapy for CLI is the surgical reconstruction and endovascular therapy or limb amputation for patients with no treatment options. Neovasculogenesis induced by mesenchymal stem cells (MSCs) therapy is a promising approach to improve CLI. Owing to their angiogenic and immunomodulatory potential, MSCs are perfect candidates for the treatment of CLI. The purpose of this study was to determine and compare the in vitro and in vivo effects of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue mesenchymal stem cells (AT-MSCs) on CLI treatment. Methods For the first step, BM-MSCs and AT-MSCs were isolated and characterized for the characteristic MSC phenotypes. Then, femoral artery ligation and total excision of the femoral artery were performed on C57BL/6 mice to create a CLI model. The cells were evaluated for their in vitro and in vivo biological characteristics for CLI cell therapy. In order to determine these characteristics, the following tests were performed: morphology, flow cytometry, differentiation to osteocyte and adipocyte, wound healing assay, and behavioral tests including Tarlov, Ischemia, Modified ischemia, Function and the grade of limb necrosis scores, donor cell survival assay, and histological analysis. Results Our cellular and functional tests indicated that during 28 days after cell transplantation, BM-MSCs had a great effect on endothelial cell migration, muscle restructure, functional improvements, and neovascularization in ischemic tissues compared with AT-MSCs and control groups. Conclusions Allogeneic BM-MSC transplantation resulted in a more effective recovery from critical limb ischemia compared to AT-MSCs transplantation. In fact, BM-MSC transplantation could be considered as a promising therapy for diseases with insufficient angiogenesis including hindlimb ischemia.

scholarly journals Immunomodulatory Effects of Adipose Tissue-Derived Stem Cells on Concanavalin A-Induced Acute Liver Injury in Mice

Cell Medicine ◽  
2017 ◽  
Vol 9 (1-2) ◽  
pp. 21-33 ◽  
Author(s):  
Yasuma Yoshizumi ◽  
Hiroshi Yukawa ◽  
Ryoji Iwaki ◽  
Sanae Fujinaka ◽  
Ayano Kanou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Mouse Model ◽  
Cell Therapy ◽  
Concanavalin A ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Immunomodulatory Effects

Cell therapy with adipose tissue-derived stem cells (ASCs) is expected to be a candidate for the treatment of fulminant hepatic failure (FHF), which is caused by excessive immune responses. In order to evaluate the therapeutic effects of ASCs on FHF, the in vitro and in vivo immunomodulatory effects of ASCs were examined in detail in the mouse model. The in vitro effects of ASCs were examined by assessing their influence on the proliferation of lymphomononuclear cells (LMCs) stimulated with three kinds of mitogens: phorbol 12-myristate 13-acetate (PMA) plus ionomycin, concanavalin A (ConA), and lipopolysaccharide (LPS). The proliferation of LMCs was efficiently suppressed in a dose-dependent manner by ASCs in the cases of PMA plus ionomycin stimulation and ConA stimulation, but not in the case of LPS stimulation. The in vivo effects of transplanted ASCs were examined in the murine FHF model induced by ConA administration. The ALT levels and histological inflammatory changes in the ConA-administered mice were apparently relieved by the transplantation of ASCs. The analysis of mRNA expression patterns in the livers indicated that the expressions of the cytokines such as Il-6, Il-10, Ifn-γ, and Tnf-α, and the cell surface markers such as Cd3γ, Cd4, Cd8α, Cd11b, and Cd11c were downregulated in the ASC-transplanted mice. The immunomodulatory and therapeutic effects of ASCs were confirmed in the mouse model both in vitro and in vivo. These suggest that the cell therapy with ASCs is beneficial for the treatment of FHF.

scholarly journals Exosomes from Gastric Cancer Suppressed Adipo-differentiation of Adipose Mesenchymal Stem Cells to Promote Cancer-associated Cachexia via miR-155/ C/EPBβ pathway

2020 ◽  
Author(s):  
Ying Liu ◽  
Dan Lin ◽  
Haiyang Zhang ◽  
Huiya Wang ◽  
Ting Deng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Luciferase Reporter ◽  
Differentiation Capacity ◽  
Healthy Donors ◽  
Adipose Mesenchymal Stem Cells ◽  
Polymerase Chain

Abstract BACKGROUNDCancer-associated cachexia (CAC) is defined as a multifactorial syndrome including depletion of adipose tissue and skeletal muscle. Adipose tissue wasting, as a key characteristic of CAC, occurs early and is related with poor survival. However, the influence of exosomes on adipo-differentiation in CAC remained be mysterious.METHODSOil-red staining, western blotting, and real-time polymerase chain reaction (RT-PCR) were used to investigate the adipo-differentiation capacity of A-MSCs from GC patients and healthy donors. Adipo-differentiation capacity of A-MSCs treated with exosomes from GES-1 or GC cell lines was also detected. To further explore the effects of exosomal miR-155 on adipo-differentiation in vitro, we carried out luciferase reporter assay. Finally, to evaluate the function of exosomal miR-155 in vivo, BALB/c mice were subcutaneously transplanted with SGC7901 cells transfected with lentivirus containing a miR-155 overexpressing (miR-155 OE) sequence or miR-155 shRNA (miR-155 KO) or control lentivirus(NC) to observe the change of adipo-differentiation of A-MSCs.RESULTSWe showed that miR-155 was high expressed in adipose mesenchymal stem cells (A-MSCs) isolated from GC patients, which exhibited significantly suppressed adipo-differentiation. Mechanistically, targeting C/EPBβ and suppressing C/EPBα and PPARγ by GC exosomal miR-155 was demonstrated to be involved in impairing the differentiation of A-MSCs into adipocytes. The expression of C/EPBβ C/EPBα and PPARγ were rescued through downregulating miR-155 in GC exosomes. Moreover, overexpression of miR-155 improved cancer cachexia in tumor-implanted mice, charactered by weight loss, tumor progression and low expression of C/EPBβ, C/EPBα, and PPARγ in A-MSCs as well as FABP4 in tumor-related adipose tissue. Decreasing level of miR-155 in implanted tumor blocked the anti-adipogenic effects of GC. CONCLUSIONGC exosomsal miR-155 suppressed adipo-differentiation of A-MSCs via targeting C/EPBβ of A-MSCs plays a crucial role in CAC.

An Animal Model for Assessing Cardiovascular Cell Therapy with Human Bone Marrow Stem Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4693-4693
Author(s):  
Cristina Touriño ◽  
Mariana Di Doménico ◽  
Carlos Rodríguez ◽  
Sebastián Adó ◽  
Rodolfo Ferrando ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Therapy ◽  
Cell Types ◽  
Capillary Density ◽  
Treated Group ◽  
Control Group ◽  
Cell Type ◽  
Human Cd34 ◽  
Cd34 Cells

Abstract Abstract 4693 Introduction: Ischemic cardiovascular diseases are still the leading cause of morbidity and mortality in the western world. Incomplete surgical myocardial revascularization is a determining factor for early flare of subsequent angina which results in lower patient survival. Cell-based cardiac therapy in the treatment of ischemic heart disease is a new concept that has been studied using numerous cell types, delivery systems, and strategies. Bone-marrow derived stem/progenitor cells (BMDC) have been used in a number of different studies in both animal and human models. Adult BMDC is composed of a multitud of cell types: hematopoietic, mesenchimal, stromal stem cells and other cell types yet to be characterized. More studies are needed to address the timing, relative concentrations, source and route of delivery of each cellular populations in animals models of myocardial ischemia. In vivo studies are clear prerequisites for clinical translation and appropriate animal models are needed. Objective: The aim of this study was to produce a xenogenic large animal model of myocardical infartation and investigate whether this model allows evaluation of angiogenic cell therapy with human BMDC. Methods: The proposed strategy was to develop myocardial ischemia in a human cell graft tolerant sheep model. Chimeric tolerant sheeps were created by human BMDC transplant into early gestational sheep fetuses during the “preimmune” stage. Human CD34+ cells (x = 315×103) were implanted in 45+3 days sheep fetuses (n = 10) by echocardiographic-guided injection (modified Zanjani model). Myocardial infarction (MI) was produced by a combined technique of surgical ligature of the first marginal of the circumflex artery and cryoablation with liquid nitrogen achieving an infarction area with total fibrotic replacement (n=8). MI was created in 1 year chimeric sheep and infarcted areas were treated with saline (control group, n=3) or 260×103 human CD34+cells (treated group, n=7). Animals were euthanazied 1 month after MI and the heart were excised for pathology study. The infarct region was divided for study into three areas respect to the center of the infarct. Blood vessels were identified by BS-1 lectin-histochemistry and capillary density determined. Results: Our results showed no differences in capillary density in the three areas studied but a slightly increase in arteriolar component in the treated group compared with the control group (not significant). Neither significant differences were observed when comparing epicardial, medium and endocardial areas. No immune rejection or graft vs. host disease were observed in all treated animals. Conclusion: This study shows that this model is a useful tool for preclinic in vivo evaluation of human cell therapy strategies in ischemic cardiovascular disease. Using human CD34+ cells at doses mentioned above our results did not showed significantly more angiogenesis and arteriogenesis than in the control group. To improve this model, further studies are needed to fully charaterize the role of dose, cell type and time for the angiogenic effect of cell-based therapies. Understanding the potentential of defined lineages of stem cells or undifferentiated progenitors, will lead to better and more focussed clinical trial designs using each cell type indenpendently or in combination, depending on which particular clinical indication is being targeted. Disclosures: No relevant conflicts of interest to declare.

401 MIGRATION AND THERAPEUTIC POTENTIAL OF PORCINE ADULT ADIPOSE-DERIVED MESENCHYMAL STEM CELLS

2010 ◽  
Vol 22 (1) ◽  
pp. 357 ◽  
Author(s):  
S. M. Wilson ◽  
E. Monaco ◽  
M. S. Goldwasser ◽  
S. G. Clark ◽  
W. L. Hurley ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Adult Stem Cells ◽  
Bone Defects ◽  
Adipose Derived Stem Cells ◽  
Subcutaneous Adipose ◽  
Time Point

Bone marrow is one current source of adult stem cells for therapeutic purposes; however, the magnitude and accessibility of subcutaneous adipose tissue in humans make it an attractive alternative. Numerous in vitro studies have been conducted to determine how these cells act in vitro, but it is imperative to determine the vast abilities of these cells in vivo. The objective of this study was to evaluate in vivo migration and bone healing ability after transplanting adipose-derived stem cells (ADSC) in a swine model. Adipose-derived stem cells were isolated from subcutaneous adipose tissue of adult Yorkshire pigs and cultured in vitro. At 80 to 90% confluence/passage 3, the cells were trypsinized and labeled in suspension with carboxyfluorescein succinimidyl ester (CFDA-SE). This project included 20 pigs weighing between 63.5 and 81.7 kg. Bilateral mandibular osteoectomies with 10-mm defects were performed on each pig. Of the 20 pigs, half received a treatment of 2.5 million CFDA-SE labeled stem cells administered directly into each defect (DI), and the remaining half received a treatment of approximately 5 million CFDA-SE labeled stem cells through an ear vein injection via catheter (EVI). The time points were 1 h and 2 and 4 wk, with 2 pigs per time with the DI and EVI treatments. Pigs were slaughtered at each time, and spleen, liver, lung, kidney, ear vein, blood, and mandible tissues were collected. Blood samples were collected from the jugular vein with EDTA and processed via flow cytometry after collection. Tissues were fixed in 10% buffered formalin for histology. Fluorescent microscopy (CFDA-SE excitation/emission is 492/517 nm) has confirmed that transplanted ADSC do indeed migrate to a site of injury or trauma. Labeled cells were also present in blood collected from the 1-h time point group. Currently, we have not seen the presence of labeled ADSC in the other tissues (spleen, liver, lung, and kidney) after the 1-h time point. We did observe that ADSC administered by DI and EVI were able to significantly heal and regenerate bone defects within 4 wk post-surgery (P < 0.05, ANOVA with F-test), in contrast to bone defects in pigs that did not receive cell injections (control). Evidence of ADSC-related healing and bone regeneration was evident by gross visualization, dual-energy x-ray absorptiometry (DXA) and micro computer tomography (microCT) analysis. The clinical implications of these results are significant for treating many diseases in which inflammation or defects exist, such as cardiac disease, neurological disease, or traumatic injuries to both soft and hard tissue. If the adult stem cells can be harvested from fat, encouraged to produce bone or cartilage, and then reinserted into defects, treatment protocols for trauma victims could be developed that would reduce the need for alternate harvesting techniques for bone. This work was support by a grant from the Illinois Regenerative Medicine Institute (IDPH # 63080017).

scholarly journals Disruption of GIP/GIPR Axis in Human Adipose Tissue Is Linked to Obesity and Insulin Resistance

2014 ◽  
Vol 99 (5) ◽  
pp. E908-E919 ◽  
Author(s):  
Victòria Ceperuelo-Mallafré ◽  
Xavier Duran ◽  
Gisela Pachón ◽  
Kelly Roche ◽  
Lourdes Garrido-Sánchez ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Stem Cells ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Human Adipose Tissue ◽  
Fat Cells ◽  
Model Assessment ◽  
Adipose Derived Stem Cells ◽  
Obese Patients ◽  
Insulin Sensitizer

Context: Glucose-dependent insulinotropic peptide (GIP) has a central role in glucose homeostasis through its amplification of insulin secretion; however, its physiological role in adipose tissue is unclear. Objective: Our objective was to define the function of GIP in human adipose tissue in relation to obesity and insulin resistance. Design: GIP receptor (GIPR) expression was analyzed in human sc adipose tissue (SAT) and visceral adipose (VAT) from lean and obese subjects in 3 independent cohorts. GIPR expression was associated with anthropometric and biochemical variables. GIP responsiveness on insulin sensitivity was analyzed in human adipocyte cell lines in normoxic and hypoxic environments as well as in adipose-derived stem cells obtained from lean and obese patients. Results: GIPR expression was downregulated in SAT from obese patients and correlated negatively with body mass index, waist circumference, systolic blood pressure, and glucose and triglyceride levels. Furthermore, homeostasis model assessment of insulin resistance, glucose, and G protein-coupled receptor kinase 2 (GRK2) emerged as variables strongly associated with GIPR expression in SAT. Glucose uptake studies and insulin signaling in human adipocytes revealed GIP as an insulin-sensitizer incretin. Immunoprecipitation experiments suggested that GIP promotes the interaction of GRK2 with GIPR and decreases the association of GRK2 to insulin receptor substrate 1. These effects of GIP observed under normoxia were lost in human fat cells cultured in hypoxia. In support of this, GIP increased insulin sensitivity in human adipose-derived stem cells from lean patients. GIP also induced GIPR expression, which was concomitant with a downregulation of the incretin-degrading enzyme dipeptidyl peptidase 4. None of the physiological effects of GIP were detected in human fat cells obtained from an obese environment with reduced levels of GIPR. Conclusions: GIP/GIPR signaling is disrupted in insulin-resistant states, such as obesity, and normalizing this function might represent a potential therapy in the treatment of obesity-associated metabolic disorders.

P3495Long-term engraftment of human CD271-positive adipose-derived stem cells with pericytic and less-aged gene profile in a mouse model of hindlimb ischemia

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
O Inoue ◽  
S Usui ◽  
A Nomura ◽  
K Yamaguchi ◽  
C Goten ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Therapy ◽  
Capillary Density ◽  
Gene Profiling ◽  
Endothelial Differentiation ◽  
Adipose Derived Stem Cells ◽  
Hindlimb Ischemia ◽  
Gene Profile ◽  
Cell Engraftment

Abstract Background Therapeutic angiogenesis using adipose-derived stem cells (ADSCs) is an attractive strategy for ischemic cardiovascular diseases. We previously reported that human CD271+ population of adipose-derived stem cells (ADSCs) promoted neovascularization with enhanced engraftment in a mouse model of hindlimb ischemia. However, whether and how CD271+ ADSCs promote the long-term engraftment is still uncertain. Purpose We aimed to examine whether the angiogenic effect and cell engraftment capacity of CD271+ ADSCs would be sustained in long-term period. Then, comparative gene profiling between CD271+ and CD271- ADSCs were analyzed. Finally, cell proliferation and endothelial differentiation assays were conducted. Methods ADSCs were isolated from subcutaneous adipose tissue of 5 patients received cardiovascular surgery. CD271+ and CD271- ADSCs were sorted from CD45-CD31-CD34+ ADSCs fraction by FACS sorting (Fig. A). Cultured CD271+ and CD271- ADSCs at passage 6 were labeled by PKH26 cell linker dye and used for xenograft experiments. Briefly, athymic nude mice were subjected to hindlimb ischemia and one million of human ADSCs were injected into the ischemic muscles. In control group, PBS was solely injected. At 2 and 5 weeks, neovascularization was evaluated by immunohistochemistry (capillary density using lectin perfusion). Cell engraftment was assessed by counting PKH26-positive cells. Furthermore, we compared gene profiling between CD271+ and CD271- ADSCs by microarray. Proliferative capacity was evaluated by colony-forming unit (CFU) assay with Giemsa staining. In endothelial differentiation assay, CD271+ and CD271- ADSCs were cultured in differentiation induction medium containing vascular endothelial growth factor for 2 weeks and stained with anti-human CD31 antibody. Results Cell therapy using CD271+ ADSCs demonstrated approximately 3-fold more enhanced neovascularization than those using CD271- ADSCs or PBS in histological analysis of capillary density at 2 weeks from cell therapy (Fig. B and C). At 5 weeks, mice treated with CD271+ ADSCs were significantly rescued from limb ischemia and this was accompanied by sustained engraftment of ADSCs (Fig. D). In microarray analysis, the differentially expressed 2167 genes were extracted to classify CD271+ and CD271- ADSCs. Pathway analysis demonstrated CD271 expression on ADSCs was associated with the pathways related to stemness and cell differentiation. Indeed, we found that genes related to cell proliferation (PI3K, Cyclin D, and Cyclin D2) were up-regulated in CD271+ ADSCs. Additionally, we found the pericytic marker nestin which was significantly up-regulated in CD271+ ADSCs. Consistent with these findings, CD271+ ADSCs were more proliferative and capable for endothelial differentiation while CD271- ADSCs were not. FACS and cell therapy experiments Conclusion These results suggest that CD271+ ADSCs possess long-term engraftment and angiogenic capacity due to their less-aged and more pericytic gene profile. Acknowledgement/Funding Japan Society for the Promotion of Science (JSPS) KAKENHI (Tokyo, Japan) Grant Number JP16H06828

scholarly journals In situ transplantation of adipose-derived stem cells via photoactivation improves glucose metabolism in obese mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Luochen Zhu ◽  
Ziqian Feng ◽  
Xin Shu ◽  
Qian Gao ◽  
Jiaqi Wu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Stem Cells ◽  
Adipose Tissue ◽  
Cell Function ◽  
Inflammatory Responses ◽  
Epididymal Adipose Tissue ◽  
Adipose Derived Stem Cells ◽  
Combined Application

Abstract Background Accumulating evidence suggests that enhanced adipose tissue macrophages (ATMs) are associated with metabolic disorders in obesity and type 2 diabetes. However, therapeutic persistence and reduced homing stem cell function following cell delivery remains a critical hurdle for the clinical translation of stem cells in current approaches. Methods We demonstrate that the effect of a combined application of photoactivation and adipose-derived stem cells (ASCs) using transplantation into visceral epididymal adipose tissue (EAT) in obesity. Cultured ASCs were derived from subcutaneous white adipose tissue isolated from mice fed a normal diet (ND). Results In diet-induced obesity, implantation of light-treated ASCs improved glucose tolerance and ameliorated systemic insulin resistance. Intriguingly, compared with non-light-treated ASCs, light-treated ASCs reduced monocyte infiltration and the levels of ATMs in EAT. Moreover, implantation of light-treated ASCs exerts more anti-inflammatory effects by suppressing M1 polarization and enhancing macrophage M2 polarization in EAT. Mass spectrometry revealed that light-treated human obese ASCs conditioned medium retained a more complete secretome with significant downregulation of pro-inflammatory cytokines and chemokines. Conclusions These data suggest that the combined application of photoactivation and ASCs using transplantation into dysfunctional adipose tissue contribute to selective suppression of inflammatory responses and protection from insulin resistance in obesity and type 2 diabetes.

scholarly journals A Pig-a conditional knock-out mice model mediated by Vav-iCre: stable GPI-deficient and mild hemolysis

2022 ◽  
Vol 11 (1) ◽  
Author(s):  
Yingying Chen ◽  
Hui Liu ◽  
Lijie Zeng ◽  
Liyan Li ◽  
Dan Lu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Animal Model ◽  
Mouse Model ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Basic Research ◽  
Mice Model ◽  
Hematopoietic Stem ◽  
Knock Out ◽  
Knock Out Mice

AbstractParoxysmal nocturnal hemoglobinuria is a clonal disease caused by PIG-A mutation of hematopoietic stem cells. At present, there is no suitable PNH animal model for basic research, therefore, it is urgent to establish a stable animal model. We constructed a Pig-a conditional knock-out mice model by ES targeting technique and Vav-iCre. The expressions of GPI and GPI-AP were almost completely absent in CKO homozygote mice, and the proportion of the deficiency remained stable from birth. In CKO heterozygote mice, the proportion of the deficiency of GPI and GPI-AP was partially absent and decreased gradually from birth until it reached a stable level at 3 months after birth and remained there for life. Compared with normal C57BL/6N mice and Flox mice, pancytopenia was found in CKO homozygous mice, and leukopenia and anemia were found in CKO heterozygotes mice. Meanwhile, in CKO mice, the serum LDH, TBIL, IBIL, complement C5b-9 levels were increased, and the concentration of plasma FHb was increased. Hemosiderin granulosa cells can be seen more easily in the spleens of CKO mice. What’s more, CKO mice had stable transcription characteristics. In conclusion, our mouse model has stable GPI-deficient and mild hemolysis, which may be an ideal in vivo experimental model for PNH.

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