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  1. Article ; Online: Effects of conditioned media derived from human Wharton's jelly mesenchymal stem cells on diabetic nephropathy and hepatopathy via modulating TGF-β and apelin signaling pathways in male rats.

    Karimi, Zeinab / Daryabor, Gholamreza / Masjedi, Fatemeh

    BMC endocrine disorders

    2024  Volume 24, Issue 1, Page(s) 6

    Abstract: Background: Diabetic nephropathy and hepatopathy are health problems described by specific renal and hepatic structure and function disturbances. The protective effects of the stem cell secretome have been shown in several kidney and liver diseases. The ...

    Abstract Background: Diabetic nephropathy and hepatopathy are health problems described by specific renal and hepatic structure and function disturbances. The protective effects of the stem cell secretome have been shown in several kidney and liver diseases. The current study aims to evaluate the capability of conditioned media derived from human Wharton's jelly mesenchymal stem cells (hWJ-MSCs-CM) to alleviate diabetic complications.
    Methods: Twenty Sprague Dawley rats were made diabetic through injection of STZ (60 mg/kg, i.p.). At week 8, diabetic rats were divided into two groups: treated [DM + hWJ-MSCs-CM (500 µl/rat for three weeks, i.p.)] and not treated (DM). At the 11th week, three groups (control, DM, and DM + hWJ-MSCs-CM) were kept in metabolic cages, and urine was collected for 24 h. The serum samples were maintained for measuring fasting blood glucose (FBG) and kidney and liver functional analysis. The left kidney and liver parts were kept at -80 °C to assess apelin and transforming growth factor-beta (TGF-β) expression. The right kidney, pancreas, and liver parts were used for histopathologic evaluation.
    Results: DM was detected by higher FBG, microalbuminuria, increased albumin/creatinine ratio, and pancreas, renal, and hepatic structural disturbances. Diabetic hepatopathy was determined by increasing liver enzymes and decreasing total bilirubin. The TGF-β gene expression was significantly upregulated in the diabetic kidney and liver tissues. Apelin gene expression was significantly downregulated in the diabetic liver tissue but did not change in kidney tissue. Administration of hWJ-MSCs-CM improved renal and hepatic functional and structural disturbances. Moreover, CM therapy significantly decreased TGF-β expression and enhanced apelin expression in the kidney and liver tissues.
    Conclusion: Human WJ-MSCs-CM may have protective effects on diabetic renal and hepatic complications. These effects may happen through the regulation of TGF-β and apelin signaling pathways.
    MeSH term(s) Animals ; Humans ; Male ; Rats ; Apelin ; Culture Media, Conditioned/pharmacology ; Diabetes Mellitus, Experimental/pathology ; Diabetic Nephropathies/etiology ; Diabetic Nephropathies/therapy ; Diabetic Nephropathies/metabolism ; Liver Diseases/metabolism ; Mesenchymal Stem Cells/metabolism ; Rats, Sprague-Dawley ; Signal Transduction ; Transforming Growth Factor beta/metabolism ; Wharton Jelly/cytology
    Chemical Substances Apelin ; Culture Media, Conditioned ; Transforming Growth Factor beta
    Language English
    Publishing date 2024-01-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 2091323-0
    ISSN 1472-6823 ; 1472-6823
    ISSN (online) 1472-6823
    ISSN 1472-6823
    DOI 10.1186/s12902-023-01535-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Toll-like receptor 9 (TLR9) genetic variants rs187084 and rs352140 confer protection from Behcet's disease among Iranians.

    Tadayon, Zahra / Shahzadeh Fazeli, Seyed Abolhassan / Gholijani, Nasser / Daryabor, Gholamreza

    BMC rheumatology

    2024  Volume 8, Issue 1, Page(s) 13

    Abstract: Background: Behcet's disease (BD) is a multisystem and multifactorial autoimmune disease characterized by relapsing episodes of oral aphthae, genital ulcers, and ocular and skin lesions. Toll-like receptor 9 (TLR9) has pro-inflammatory roles and its ... ...

    Abstract Background: Behcet's disease (BD) is a multisystem and multifactorial autoimmune disease characterized by relapsing episodes of oral aphthae, genital ulcers, and ocular and skin lesions. Toll-like receptor 9 (TLR9) has pro-inflammatory roles and its genetic variants might be involved in the pathogenesis of inflammatory diseases.  METHODS: Two hundred five BD patients and 207 age and sex-matched healthy controls were evaluated for TLR9 single nucleotide polymorphisms - 1486 T/C (rs187084) and + 2848:G/A (rs352140) using polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR).
    Results: Healthy individuals had a significantly higher frequency of rs187084 AG and AG + GG genotypes than BD patients (p = 0.02 and p = 0.018; respectively). Of interest, healthy males had a significantly higher frequency of rs187084 AG + GG genotype and G allele than male BD patients (p = 0.035 and p = 0.045; respectively). However, rs187084 AG genotype and G allele frequencies were significantly higher in male patients with genital aphthous (p = 0.01 and p = 0.046; respectively). Furthermore, a significantly higher frequency of rs352140 CT and TT + CT genotypes was detected in healthy individuals than in BD patients (p = 0.01, and p = 0.032; respectively). Such results were also seen in healthy females than female patients (p = 0.001, and p = 0.004; respectively). Haplotype analysis revealed a significantly higher frequency of A-C and G-C haplotypes among patients and healthy subjects, respectively (p = 0.002 and p = 0.000; respectively).
    Conclusion: Our data suggested that rs187084 AG and AG + GG genotypes and rs352140 CT and TT + CT genotypes protect Iranian individuals from BD but rs187084 AG genotype and G allele predispose male BD individuals to genital aphthous. However, additional studies are required to verify these results.
    Language English
    Publishing date 2024-03-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 2918121-5
    ISSN 2520-1026 ; 2520-1026
    ISSN (online) 2520-1026
    ISSN 2520-1026
    DOI 10.1186/s41927-024-00382-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A review of the critical role of vitamin D axis on the immune system.

    Daryabor, Gholamreza / Gholijani, Nasser / Kahmini, Fatemeh Rezaei

    Experimental and molecular pathology

    2023  Volume 132-133, Page(s) 104866

    Abstract: In recent years, the physiological and molecular functions of vitamin D (Vit-D) have been deeply investigated. At first, Vit-D was considered a regulator of mineral and skeletal homeostasis. However, due to the extensive-expression pattern of Vit-D ... ...

    Abstract In recent years, the physiological and molecular functions of vitamin D (Vit-D) have been deeply investigated. At first, Vit-D was considered a regulator of mineral and skeletal homeostasis. However, due to the extensive-expression pattern of Vit-D receptor (VDR) in almost every non-skeletal cell, Vit-D is considered mainly a multifunctional agent with broad effects on various tissues, notably the immune system. The expression of VDR in immune cells such as dendritic cells, monocyte/macrophage, neutrophils, B cells and T cells has been well demonstrated. Besides, such immune cells are capable of metabolizing the active form of Vit-D which means that it can module the immune system in both paracrine and autocrine manners. Vit-D binding protein (DBP), that regulates the levels and homeostasis of Vit-D, is another key molecule capable of modulating the immune system. Recent studies indicate that dysregulation of Vit-D axis, variations in the DBP and VDR genes, and Vit-D levels might be risk factors for the development of autoimmune disease. Here, the current evidence regarding the role of Vit-D axis on the immune system, as well as its role in the development of autoimmune disease will be clarified. Further insight will be given to those studies that investigated the association between single nucleotide polymorphisms of DBP and VDR genes with autoimmune disease susceptibility.
    MeSH term(s) Humans ; Vitamin D/genetics ; Receptors, Calcitriol/genetics ; Receptors, Calcitriol/metabolism ; Immune System/metabolism ; Autoimmune Diseases
    Chemical Substances Vitamin D (1406-16-2) ; Receptors, Calcitriol
    Language English
    Publishing date 2023-08-17
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 207655-x
    ISSN 1096-0945 ; 0014-4800
    ISSN (online) 1096-0945
    ISSN 0014-4800
    DOI 10.1016/j.yexmp.2023.104866
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: SARS-CoV-2 mechanisms of cell tropism in various organs considering host factors.

    Behboudi, Emad / Nooreddin Faraji, Seyed / Daryabor, Gholamreza / Mohammad Ali Hashemi, Seyed / Asadi, Maryam / Edalat, Fahime / Javad Raee, Mohammad / Hatam, Gholamreza

    Heliyon

    2024  Volume 10, Issue 4, Page(s) e26577

    Abstract: A critical step in the drug design for SARS-CoV-2 is to discover its molecular targets. This study comprehensively reviewed the molecular mechanisms of SARS-CoV-2, exploring host cell tropism and interaction targets crucial for cell entry. The findings ... ...

    Abstract A critical step in the drug design for SARS-CoV-2 is to discover its molecular targets. This study comprehensively reviewed the molecular mechanisms of SARS-CoV-2, exploring host cell tropism and interaction targets crucial for cell entry. The findings revealed that beyond ACE2 as the primary entry receptor, alternative receptors, co-receptors, and several proteases such as TMPRSS2, Furin, Cathepsin L, and ADAM play critical roles in virus entry and subsequent pathogenesis. Additionally, SARS-CoV-2 displays tropism in various human organs due to its diverse receptors. This review delves into the intricate details of receptors, host proteases, and the involvement of each organ. Polymorphisms in the ACE2 receptor and mutations in the spike or its RBD region contribute to the emergence of variants like Alpha, Beta, Gamma, Delta, and Omicron, impacting the pathogenicity of SARS-CoV-2. The challenge posed by mutations raises questions about the effectiveness of existing vaccines and drugs, necessitating consideration for updates in their formulations. In the urgency of these critical situations, repurposed drugs such as Camostat Mesylate and Nafamostat Mesylate emerge as viable pharmaceutical options. Numerous drugs are involved in inhibiting receptors and host factors crucial for SARS-CoV-2 entry, with most discussed in this review. In conclusion, this study may provide valuable insights to inform decisions in therapeutic approaches.
    Language English
    Publishing date 2024-02-20
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2835763-2
    ISSN 2405-8440
    ISSN 2405-8440
    DOI 10.1016/j.heliyon.2024.e26577
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Obesity and Adipose Tissue-derived Cytokines in the Pathogenesis of Multiple Sclerosis.

    Daryabor, Gholamreza / Amirghofran, Zahra / Gholijani, Nasser / Bemani, Peyman

    Endocrine, metabolic & immune disorders drug targets

    2022  Volume 22, Issue 12, Page(s) 1217–1231

    Abstract: Multiple sclerosis (MS) is a chronic autoimmune neurodegenerative disease of the central nervous system (CNS) characterized by demyelination, neuronal loss, and permanent neurological impairments. The etiology of MS is not clearly understood, but ... ...

    Abstract Multiple sclerosis (MS) is a chronic autoimmune neurodegenerative disease of the central nervous system (CNS) characterized by demyelination, neuronal loss, and permanent neurological impairments. The etiology of MS is not clearly understood, but genetics and environmental factors can affect the susceptibility of individuals. Obesity or a body mass index of (BMI) > 30 kg/m2 is associated with serious health consequences such as lipid profile abnormalities, hypertension, type 2 diabetes mellitus, reduced levels of vitamin D, and a systemic lowgrade inflammatory state. The inflammatory milieu can negatively affect the CNS and promote MS pathogenesis due in part to the increased blood-brain barrier permeability by the actions of adipose tissue-derived cytokines or adipokines. By crossing the blood-brain barrier, the pro-inflammatory adipokines such as leptin, resistin, and visfatin activate the CNS-resident immune cells, and promote the inflammatory responses; subsequently, demyelinating lesions occur in the white matter of the brain and spinal cord. Therefore, better knowledge of the adipokines' role in the induction of obesity-related chronic inflammation and subsequent events leading to the dysfunctional blood-brain barrier is essential. In this review, recent evidence regarding the possible roles of obesity and its related systemic low-grade inflammation, and the roles of adipokines and their genetic variants in the modulation of immune responses and altered blood-brain barrier permeability in MS patients, has been elucidated. Besides, the results of the current studies regarding the potential use of adipokines in predicting MS disease severity and response to treatment have been explored.
    MeSH term(s) Humans ; Leptin ; Resistin ; Nicotinamide Phosphoribosyltransferase ; Multiple Sclerosis/etiology ; Diabetes Mellitus, Type 2/complications ; Neurodegenerative Diseases/pathology ; Adipose Tissue/pathology ; Adipokines ; Obesity ; Cytokines ; Inflammation/pathology ; Vitamin D ; Lipids
    Chemical Substances Leptin ; Resistin ; Nicotinamide Phosphoribosyltransferase (EC 2.4.2.12) ; Adipokines ; Cytokines ; Vitamin D (1406-16-2) ; Lipids
    Language English
    Publishing date 2022-02-15
    Publishing country United Arab Emirates
    Document type Review ; Journal Article
    ZDB-ID 2228325-0
    ISSN 2212-3873 ; 1871-5303
    ISSN (online) 2212-3873
    ISSN 1871-5303
    DOI 10.2174/1871530322666220215110041
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Single nucleotide polymorphisms rs7799039 and rs2167270 in leptin gene and elevated serum levels of adiponectin predispose Iranians to Behçet's disease.

    Kahmini, Fatemeh Rezaei / Gholijani, Nasser / Amirghofran, Zahra / Daryabor, Gholamreza

    Cytokine

    2022  Volume 162, Page(s) 156100

    Abstract: Background: Behçet's Disease (BD) is a chronic autoimmune disease with unknown etiology. Adipokines due to their roles in the regulation of immune responses might be important in the induction and progression of BD.: Subjects and methods: This case- ... ...

    Abstract Background: Behçet's Disease (BD) is a chronic autoimmune disease with unknown etiology. Adipokines due to their roles in the regulation of immune responses might be important in the induction and progression of BD.
    Subjects and methods: This case-control study included 340 patients with BD and 310 healthy controls. Single nucleotide polymorphisms (SNPs) in adiponectin (rs266729 and rs1501299) and leptin (rs7799039 and rs2167270) genes were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and serum levels of adipokines were measured using enzyme-linked immunosorbent assay (ELISA).
    Results: A higher frequency of leptin rs7799039 GG, AG, and AG +GG genotypes and G allele was revealed in patients. Besides, patients had more leptin rs2167270 AG and AG +AA genotypes and A allele. Furthermore, rs2167270 AA genotype and A allele were more frequently seen in total and female patients who had genital aphthous. Patients had significantly more serum levels of adiponectin while those with genital aphthous had significantly more leptin levels. No significant association was observed between genotypes and alleles of adiponectin SNPs and BD.
    Conclusion: Our findings indicated that leptin gene polymorphisms might predispose Iranian individuals to BD. Besides, elevated serum levels of adiponectin might facilitate BD pathogenesis.
    MeSH term(s) Humans ; Female ; Polymorphism, Single Nucleotide/genetics ; Iran ; Behcet Syndrome/genetics ; Adiponectin/genetics ; Leptin/genetics ; Genetic Predisposition to Disease ; Case-Control Studies ; Genotype ; Adipokines/genetics ; Gene Frequency/genetics
    Chemical Substances Adiponectin ; Leptin ; Adipokines
    Language English
    Publishing date 2022-12-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 1018055-2
    ISSN 1096-0023 ; 1043-4666
    ISSN (online) 1096-0023
    ISSN 1043-4666
    DOI 10.1016/j.cyto.2022.156100
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: In vitro-derived insulin-producing cells modulate Th1 immune responses and induce IL-10 in streptozotocin-induced mouse model of pancreatic insulitis.

    Daryabor, Gholamreza / Shiri, Esmaeil Hashemi / Amirghofran, Zahra / Kamali-Sarvestani, Eskandar

    Hepatobiliary & pancreatic diseases international : HBPD INT

    2021  Volume 20, Issue 4, Page(s) 376–382

    Abstract: Background: Insulitis is defined by the presence of immune cells infiltrating in the pancreatic islets that might progress into the complete β-cell loss. The immunomodulatory properties of bone marrow-derived mesenchymal stem cells (BM-MSCs) have ... ...

    Abstract Background: Insulitis is defined by the presence of immune cells infiltrating in the pancreatic islets that might progress into the complete β-cell loss. The immunomodulatory properties of bone marrow-derived mesenchymal stem cells (BM-MSCs) have attracted much attention. This study aimed to evaluate the possible immunomodulatory effects of rat BM-MSCs and MSCs-derived insulin-producing cells (IPCs) in a mouse model of pancreatic insulitis.
    Methods: Insulitis was induced in BALB/c mice using five consecutive doses of streptozotocin. MSCs or IPCs were directly injected into the pancreas of mice and their effects on the expression of Th subsets-related genes were evaluated.
    Results: Both BM-MSCs and IPCs significantly reduced the expression of pancreatic Th1-related IFN-γ (P < 0.001 and P < 0.05, respectively) and T-bet genes (both P < 0.001). Moreover, the expression of IL-10 gene was significantly increased in IPC-treated compared to BM-MSC- or PBS-treated mice (P < 0.001 both comparisons).
    Conclusions: BM-MSCs and IPCs could successfully suppress pathologic Th1 immune responses in the mouse model of insulitis. However, the marked increase in IL-10 gene expression by IPCs compared to BM-MSCs suggests that their simultaneous use at the initial phase of autoimmune diabetes might be a better option to reduce inflammation but these results need to be verified by further experiments.
    MeSH term(s) Animals ; Cell Differentiation ; Disease Models, Animal ; Immunity ; Insulin ; Interleukin-10/genetics ; Mice ; Mice, Inbred BALB C ; Pancreas ; Rats ; Streptozocin
    Chemical Substances Insulin ; Interleukin-10 (130068-27-8) ; Streptozocin (5W494URQ81)
    Language English
    Publishing date 2021-04-04
    Publishing country Singapore
    Document type Journal Article
    ZDB-ID 2241386-8
    ISSN 1499-3872
    ISSN 1499-3872
    DOI 10.1016/j.hbpd.2021.03.008
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  8. Article ; Online: The effects of ankle-foot orthoses with plantar flexion stop and plantar flexion resistance using rocker-sole shoes on stroke gait: A randomized-controlled trial.

    Daryabor, Aliyeh / Aminian, Gholamreza / Arazpour, Mokhtar / Baniasad, Mina / Yamamoto, Sumiko

    Turkish journal of physical medicine and rehabilitation

    2021  Volume 67, Issue 4, Page(s) 449–461

    Abstract: Objectives: This study aims to evaluate the effect of two ankle-foot orthoses (AFOs), AFO with plantar flexion stop (AFO-PlfS), and AFO with plantar flexion resistance (AFO-PlfR), while wearing standard shoes and rocker-sole shoes.: Patients and ... ...

    Abstract Objectives: This study aims to evaluate the effect of two ankle-foot orthoses (AFOs), AFO with plantar flexion stop (AFO-PlfS), and AFO with plantar flexion resistance (AFO-PlfR), while wearing standard shoes and rocker-sole shoes.
    Patients and methods: Between November 2017 and July 2018, in this randomized-controlled study, a total of 20 stroke patients (8 males, 12 females; mean age: 48.1 years; range, 33 to 65 years) in chronic phase were randomized to AFO groups (AFO-PlfS group, n=10 and AFO-PlfR group, n=10). Each group received the allocated AFO along with two kinds of shoes (standard shoe and rocker shoe) for a two-week adaptation. Two effects were separately evaluated: The orthotic effect and rocker shoe effect were defined as the evaluation of using an AFO wearing standard shoe compared to only standard shoe, and evaluation of using an AFO wearing rocker shoe compared to an AFO wearing standard shoe, respectively. The gait of each group was measured by three-dimensional motion analysis.
    Results: A significant orthotic effect was found in both AFO groups in spatiotemporal parameters and maximum ankle dorsiflexion in the single-support phase. Additionally, the AFO-PlfR group showed a significant improvement in the parameters related to the first rocker of gait, but not for AFO-PlfS group concerning the orthotic effect. The rocker shoe effect was found in significant reduction of peak ankle plantar flexor moment and power ankle generation during preswing for both AFO groups.
    Conclusion: According to the orthotic effect, an AFO-PlfR can create better function in the improvement of parameters related to the first rocker. Although a rocker shoe can facilitate rollover for weight progression in the third rocker of gait, it cannot make a strong push-off function in stroke survivors.
    Language English
    Publishing date 2021-12-01
    Publishing country Turkey
    Document type Journal Article
    ZDB-ID 2712472-1
    ISSN 2587-1250 ; 2587-1250 ; 1308-6316
    ISSN (online) 2587-1250
    ISSN 2587-1250 ; 1308-6316
    DOI 10.5606/tftrd.2021.6448
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: An update on immune dysregulation in obesity-related insulin resistance.

    Daryabor, Gholamreza / Kabelitz, Dieter / Kalantar, Kurosh

    Scandinavian journal of immunology

    2019  Volume 89, Issue 4, Page(s) e12747

    Abstract: Obesity is associated with chronic low-grade inflammation of the adipose tissue (AT) that might develop into systemic inflammation, insulin resistance (IR) and an increased risk of type 2 diabetes mellitus (T2DM) in severe obese rodents and humans. In ... ...

    Abstract Obesity is associated with chronic low-grade inflammation of the adipose tissue (AT) that might develop into systemic inflammation, insulin resistance (IR) and an increased risk of type 2 diabetes mellitus (T2DM) in severe obese rodents and humans. In the lean state, small normal adipocytes and AT macrophages interact with each other to maintain metabolic homeostasis but during obesity, enlarged adipocytes secrete inflammatory mediators and express immune receptors to recruit immune cells and aggravate the inflammation. The better understanding of the obesity-related inflammatory milieu and the sequential events leading to IR could be helpful in designing new preventive and therapeutic strategies. The present review will discuss the cellular and molecular abnormalities participating in the pathogenesis of obesity in obese individuals as well as high-fat diet (HFD)-fed mice, a mouse model of obesity.
    MeSH term(s) Animals ; Diabetes Mellitus, Type 2/immunology ; Diet, High-Fat ; Disease Models, Animal ; Homeostasis ; Humans ; Inflammation/immunology ; Insulin Resistance/immunology ; Mice ; Obesity/immunology
    Language English
    Publishing date 2019-01-29
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 120476-2
    ISSN 1365-3083 ; 0300-9475
    ISSN (online) 1365-3083
    ISSN 0300-9475
    DOI 10.1111/sji.12747
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  10. Article ; Online: A simple method for the generation of insulin producing cells from bone marrow mesenchymal stem cells.

    Daryabor, Gholamreza / Shiri, Esmaeil Hashemi / Kamali-Sarvestani, Eskandar

    In vitro cellular & developmental biology. Animal

    2019  Volume 55, Issue 6, Page(s) 462–471

    Abstract: To produce insulin-producing cells (IPCs) from bone marrow mesenchymal stem cells (BM-MSCs) using a simple and cost effective method. During the initial 7 days of three-dimensional (3D) culture, BM-MSCs were cultured on 1% agar or agarose to form ... ...

    Abstract To produce insulin-producing cells (IPCs) from bone marrow mesenchymal stem cells (BM-MSCs) using a simple and cost effective method. During the initial 7 days of three-dimensional (3D) culture, BM-MSCs were cultured on 1% agar or agarose to form multicellular spheroids. Spheroids and spheroid-derived single cells (SS and SSC, respectively) were cultured in the absence of any proteinaceous growth factor in a simple specific medium for a further 7 d. The insulin content of the differentiated cells was evaluated at the mRNA and protein levels. Furthermore, the expression of pancreatic beta cells-related genes other than INS as well as the in vitro responses of IPCs to different glucose concentrations were investigated. Cellular clusters generated on agar and SS conditions (agar+SS-IPCs) stained better with beta cell specific stains and were more reactive to serum-containing insulin reactive antibodies compared with agarose-SS-IPCs. Gene expression analysis revealed that in comparison to agarose + SS-IPCs, agar+SS-IPCs expressed significantly higher levels of INS-1, INS-2, PDX-1, NKX6.1, and XBP-1. Of interest, agar+SS-IPCs expressed 2215.3 ± 120.8-fold more INS-1 gene compared to BM-MSCs. The expression of β-cell associated genes was also higher in agar+SS-IPCs compared to the agar+SSC-IPCs. Moreover, the expression of INS-1 gene was significantly higher in agar+SS-IPCs compared with agar+SSC-IPCs after culture in media with high concentration of glucose. Compared to the most expensive and time-consuming protocols, 3D culture of MSCs on agar followed by 2D culture of cellular clusters in a minimally supplemented high glucose media produced highly potent IPCs which may pay the way to the treatment of diabetic patients.
    MeSH term(s) Agar ; Animals ; Bone Marrow Cells/cytology ; Cell Differentiation ; Gene Expression Regulation ; Humans ; Insulin/metabolism ; Insulin-Secreting Cells/physiology ; Male ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/metabolism ; Rats, Sprague-Dawley ; Spheroids, Cellular/cytology ; Tissue Culture Techniques/methods ; Umbilical Cord/cytology
    Chemical Substances Insulin ; Agar (9002-18-0)
    Language English
    Publishing date 2019-05-20
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1077810-x
    ISSN 1543-706X ; 0883-8364 ; 1071-2690
    ISSN (online) 1543-706X
    ISSN 0883-8364 ; 1071-2690
    DOI 10.1007/s11626-019-00358-z
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