scholarly journals Comparisons of Differentiation Potential in Human Mesenchymal Stem Cells from Wharton’s Jelly, Bone Marrow, and Pancreatic Tissues

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Shih-Yi Kao ◽  
Jia-Fwu Shyu ◽  
Hwai-Shi Wang ◽  
Chi-Hung Lin ◽  
Cheng-Hsi Su ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Blood Glucose ◽  
Diabetic Rats ◽  
Differentiation Potential ◽  
Wharton's Jelly ◽  
Glucose Levels ◽  
Blood Glucose Levels

Background. Type 1 diabetes mellitus results from autoimmune destruction ofβ-cells. Insulin-producing cells (IPCs) differentiated from mesenchymal stem cells (MSCs) in human tissues decrease blood glucose levels and improve survival in diabetic rats. We compared the differential ability and the curative effect of IPCs from three types of human tissue to determine the ideal source of cell therapy for diabetes.Methods. We induced MSCs from Wharton’s jelly (WJ), bone marrow (BM), and surgically resected pancreatic tissue to differentiate into IPCs. Thein vitrodifferential function of these IPCs was compared by insulin-to-DNA ratios and C-peptide levels after glucose challenge.In vivocurative effects of IPCs transplanted into diabetic rats were monitored by weekly blood glucose measurement.Results. WJ-MSCs showed better proliferation and differentiation potential than pancreatic MSCs and BM-MSCs.In vivo, WJ-IPCs significantly reduced blood glucose levels at first week after transplantation and maintained significant decrease till week 8. BM-IPCs reduced blood glucose levels at first week but gradually increased since week 3. In resected pancreas-IPCs group, blood glucose levels were significantly reduced till two weeks after transplantation and gradually increased since week 4.Conclusion. WJ-MSCs are the most promising stem cell source forβ-cell regeneration in diabetes treatment.

scholarly journals Induced Hyperglycemia in Mice is Controlled Following the Microfluidic System- Assisted Transplantation of Stem Cells-derived Insulin-producing Cells Transduced with miRNA

2020 ◽  
Author(s):  
Adele Soltani ◽  
Masoud Soleimani ◽  
Mohammad Adel Ghiass ◽  
Seyed Ehsan Enderami ◽  
Shahram Rabbani ◽  
...  
Keyword(s):  
Stem Cells ◽  
Blood Glucose ◽  
Functional Condition ◽  
Microfluidic System ◽  
Diabetic Mice ◽  
Differentiation Potential ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Insulin Producing Cells

Abstract BackgroundCell-based therapy is a promising approach for the treatment of type 1 diabetes mellitus. Identification of stem cells as progenitor stem cells with differentiation potential to Insulin-producing cells (IPCs) and their application is an emerging issue. Different strategies have been used to support the cell survival and their specific functions to control hyperglycemia condition. Novel technology systems using appropriate materials/fibres can improve the cell transplantation.MethodsIn the present study, glucose-sensitive insulin-producing cells (IPCs) were differentiated from adipose-derived stem cells (ADSCs) transduced with miR-375 and anti-miR-7 to enhance the functions of the cells. The survival rate of the cells was also improved by using a microfluidic system prior to in vivo transplantation of the IPCs. The contribution of miR-375 with the anti-miR-7 in mature IPCs derived from ADSCs resulted in gaining the function of the cells as judged by insulin productionResultsAfter adopting a stable functional condition of the IPCs, the cells were used for in vivo grafting to diabetic mice which resulted in a substantial drop (5-folds) in blood glucose during four weeks of grafting. The pattern of blood glucose levels in the mice receiving fiber entrapped IPCs was similar to that of non-diabetic mice and blood glucose declined in animals treated with fiber-entrapped-IPCs. Blood insulin was elevated (2-folds) in diabetic mice received transplant of fiber-entrapped-IPCs carrying miR-375 and anti-miR-7 after five weeks of transplantation when compared to the untreated diabetic mice. For the first time, this study showed that the two-component microfluidic system is useful for supporting the Collagen-Alginate fiber-entrapped IPCs and the miRNAs-based cell therapy.ConclusionsOverall data show that the IPCs encapsulation by the microfluidic system can support the cells in terms of morphology and biological function and their efficiency for controlling the hyperglycemia condition in diabetic mice.

Purinergic Stimulation of Human Bone Marrow-Derived Mesenchymal Stem Cells Modulate Their Function and Differentiation Potential.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3848-3848
Author(s):  
Marilena Ciciarello ◽  
Valentina Salvestrini ◽  
Davide Ferrari ◽  
Sara Gulinelli ◽  
Roberta Zini ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Transcription Factor ◽  
Human Bone ◽  
Differentiation Potential ◽  
Qrt Pcr ◽  
Differentiated Cells

Abstract Abstract 3848 Introduction: Human bone marrow derived Mesenchymal Stem Cells (hMSCs) are adult multipotent cells. hMSCs differentiate in vitro and in vivo into several tissue lineages originating from the three germinal layers making them attractive candidates for bioengineering and cellular therapy. Thus, it seems of great relevance to search putative messengers and signalling able to modulate their proliferation and differentiation. Nucleotides triphosphates are extracellular messengers binding to specific receptors (P2Rs) that modulate cell functions depending on the cell type. Controversial information is available on P2 expression and activity in hMSCs. Methods and Results: Here we found that hMSCs expressed several P2R subtypes. hMSCs were very resistant to the cytotoxic effects of high concentrations of ATP, as demonstrated by the lack of morphological and mitochondrial changes or release of intracellular markers of cell death. Gene expression profiling revealed that ATP treatment down-regulated cell proliferation and up-regulated cell migration genes in hMSCs. Functional studies confirmed the inhibitory activity of ATP on proliferation and clonogenic ability of hMSCs. Furthermore, ATP potentiated the chemotactic response of hMSCs to the chemokine CXCL12, and increased their spontaneous migration. In vivo, xenotransplant experiments showed that the homing capacity of hMSCs to murine bone marrow was increased by ATP pre-treatment. Moreover, ATP increased pro-inflammatory cytokines production (IL-2, IFN-g, IL-12p70), while decreased secretion of the anti-inflammatory cytokine IL-10. This finding was associated with the reduced ability of ATP-treated hMSC of inhibiting T-cell proliferation. Microarrays data suggested that several genes implicated in hMSC differentiation can be modulated by ATP treatment. To further investigate this issue, hMSCs cells were cultured under adipogenic or osteogenic conditions and were transiently exposed to ATP before starting differentiation or continuously exposed to ATP for the first 3 days of differentiation induction. We demonstrated that adipogenesis-related accumulation of lipids, analyzed by Oil red O staining, was more evident in ATP treated cultures. Furthermore, quantitative real time PCR (qRT-PCR) assay showed that mRNA expression of PPARg, a transcription factor early up-regulated during adipogenesis, was significantly increased in hMSCs differentiated cells treated with ATP. In osteogenic condition, analysis of mineralized area through Alizarin Red staining, indicated that ATP treatment enhanced the extent of mineralization compared to untreated control. The expression of RUNX2, a key transcription factor in osteogenesis, analyzed by qRT-PCR in differentiated cells confirmed data obtained in Alizarin-based assay. Conclusions: These data demonstrated that purinergic signalling modulates biological functions and differentiation potential of hMSCs. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells Stimulated by Deferoxamine Accelerate Cutaneous Wound Healing by Promoting Angiogenesis

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Jianing Ding ◽  
Xin Wang ◽  
Bi Chen ◽  
Jieyuan Zhang ◽  
Jianguang Xu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Wound Repair ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Diabetic Rats

The exosomes are derived from mesenchymal stem cells (MSCs) and may be potentially used as an alternative for cell therapy, for treating diabetic wounds, and aid in angiogenesis. This study, aimed to investigate whether exosomes originated from bone marrow-derived MSCs (BMSCs) preconditioned by deferoxamine (DFO-Exos) exhibited superior proangiogenic property in wound repair and to explore the underlying mechanisms involved. Human umbilical vein endothelial cells (HUVECs) were used for assays involving cell proliferation, scratch wound healing, and tube formation. To test the effects in vivo, streptozotocin-induced diabetic rats were established. Two weeks after the procedure, histological analysis was used to measure wound-healing effects, and the neovascularization was evaluated as well. Our findings demonstrated that DFO-Exos activate the PI3K/AKT signaling pathway via miR-126 mediated PTEN downregulation to stimulate angiogenesis in vitro. This contributed to enhanced wound healing and angiogenesis in streptozotocin-induced diabetic rats in vivo. Our results suggest that, in cell-free therapies, exosomes derived from DFO preconditioned stem cells manifest increased proangiogenic ability.

Modulation of GLUT4 expression by oral administration of Mg2+ to control sugar levels in STZ-induced diabetic rats

2014 ◽  
Vol 92 (6) ◽  
pp. 438-444 ◽  
Author(s):  
Haniah Solaimani ◽  
Nepton Soltani ◽  
Kianoosh MaleKzadeh ◽  
Shahla Sohrabipour ◽  
Nina Zhang ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Magnesium Sulfate ◽  
Mrna Expression ◽  
Insulin Level ◽  
Diabetic Rats ◽  
In Vivo Studies ◽  
Glucose Levels ◽  
Blood Glucose Levels

It has been previously shown that oral magnesium administration decreases the levels of glucose in the plasma. However, the mechanisms are not fully understood. The aim of this study was to determine the potential role of GLUT4 on plasma glucose levels by orally administering magnesium sulfate to diabetic rats. Animals were distributed among 4 groups (n = 10 rats per group): one group served as the non-diabetic control, while the other groups had diabetes induced by streptozotocin (intraperitoneal (i.p.) injection). The diabetic rats were either given insulin by i.p. injection (2.5 U·(kg body mass)–1·day–1), or magnesium sulfate in their drinking water (10 g·L–1). After 8 weeks of treatment, we conducted an i.p. glucose tolerance test (IPGTT), measured blood glucose and plasma magnesium levels, and performed in-vitro and in-vivo insulin level measurements by radioimmunoassay. Gastrocnemius (leg) muscles were isolated for the measurement of GLU4 mRNA expression using real-time PCR. Administration of magnesium sulfate improved IPGTT and lowered blood glucose levels almost to the normal range. However, the insulin levels were not changed in either of the in-vitro or in-vivo studies. The expression of GLU4 mRNA increased 23% and 10% in diabetic magnesium-treated and insulin-treated groups, respectively. Our findings suggest that magnesium lowers blood glucose levels via increased GLU4 mRNA expression, independent to insulin secretion.

scholarly journals Paradoxical refractoriness developing with the allogeneic transfer of splenic lymphocyte total RNA from animals with treated alloxan diabetes to animals with untreated diabetes

2020 ◽  
pp. 37-46
Author(s):  
Н.М. Геворкян ◽  
Н.В. Тишевская ◽  
А.Г. Бабаева
Keyword(s):  
Diabetes Mellitus ◽  
Bone Marrow ◽  
Blood Glucose ◽  
Alloxan Diabetes ◽  
Diabetic Rats ◽  
Female Rats ◽  
Diabetes Group ◽  
Total Rna ◽  
Glucose Levels ◽  
Blood Glucose Levels

Ранее нами было показано, что препараты аллогенной суммарной РНК, выделенной из лимфоидных и стволовых клеток здоровых животных, вызывают нормализацию уровня глюкозы крови у крыс со стойким аллоксановым сахарным диабетом. Цель исследования -- выяснение влияния суммарной РНК лимфоцитов селезенки крыс, ранее перенесших стойкий аллоксановый диабет, на особенности течения эксперименального аллоксанового диабета у животных. Методика. Эксперимент выполнен на 35 белых беспородных крысах-самках массой 250-280 г: 5 интактных животных, 20 - с экспериментальным аллоксановым сахарным диабетом и 10 животных, ранее перенесших стойкий аллоксановый диабет, у которых уровень глюкозы крови был полностью нормализован введением суммарных РНК клеток костного мозга, селезенки и поджелудочной железы. Диабет у этих животных моделировали однократным подкожным введением полного адъюванта Фрейнда (0,5 мл на крысу) и последующим подкожным введением аллоксана тригидрата в дозе 200 мг/кг. Достигнутая нормогликемия у животных подтверждалась в течение последующих 60 сут. Из селезенок и костного мозга этих животных методом фенол-хлороформной экстракции была выделена суммарная РНК. На 20 крысах с экспериментальным аллоксановым сахарным диабетом изучали эффекты однократного внутрибрюшинного введения полученной суммарной РНК (15 мкг/100 г массы тела животного). Результаты. Обнаружено, что при введении суммарной РНК селезенки крыс, ранее перенесших аллоксановый диабет, животным с аллоксановым диабетом у последних развивалась стойкая и длительная рефрактерность к лечению терапевтическими препаратами РНК. Заключение. 1. Выявлен феномен повышенной чувствительности крыс с аллоксановым диабетом к действию суммарной РНК селезенки животных, ранее перенесших аллоксановый диабет. 2. Предполагаемой причиной рефрактерности является клональный компонент суммарной РНК CD8+ Т-лимфоцитов памяти из селезенки животных, ранее перенесших аллоксановый диабет. 3. Предполагается наличие механизма адресного взаимодействия отдельных компонентов суммарной РНК селезенки крыс, ранее перенесших аллоксановый диабет, с их лимфоцитами-мишенями в организме реципиентов с аллоксановым диабетом. Introduction. Earlier we have shown that preparations of allogenic total RNA from lymphoid and stem cells of healthy animals contribute to normalization of blood glucose levels in white outbred rats with persistent alloxan-induced diabetes mellitus. The aim of this study was to find out whether allogenic total RNA isolated from the spleen of rats treated for alloxan diabetes affects its course, as determined by changes in blood glucose, in animals with persistent alloxan diabetes. Methods. Experiments were performed on 35 white outbred female rats weighing 250-280 g. Rats were divided into intact animals (n=5), rats with experimental alloxan diabetes mellitus (n=20), and rats after persistent alloxan diabetes (n=10) whose blood glucose level had been completely normalized by administrating total RNA of bone marrow, splenic, and pancreatic cells (post-diabetes group). Diabetes mellitus was modeled with a single subcutaneous (s.c.) injection of complete Freund’s adjuvant (0.5 ml) followed by a s.c. injection of alloxan trihydrate (200 mg/kg). Achievement of normoglycemia in animals of the post-diabetes group was confirmed over the next 60 days. Then total RNA was isolated from their spleen and bone marrow by phenol-chloroform extraction, and the effect of a single intraperitoneal injection of total RNA (15 μg/100 g body weight) was studied. Results. Administration of splenic total RNA from rats previously treated for alloxan diabetes to animals with alloxan diabetes resulted in development of stable and prolonged refractoriness of diabetic rats to the treatment with therapeutic RNA preparations [11]. Conclusions. This study discovered a phenomenon of hypersensitivity of rats with alloxan diabetes to the diabetogenic effect of total RNA from animals that had previously had alloxan diabetes. Apparently, this refractoriness was caused by the clonal component of the total RNA of CD8 + T memory lymphocytes from the spleen of post-diabetes animals. A mechanism is proposed for the interaction between individual components of splenic total RNA from post-diabetes rats and their target lymphocytes in recipients with alloxan diabetes.

scholarly journals Bone Marrow Stem Cell as a Potential Treatment for Diabetes

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Ming Li ◽  
Susumu Ikehara
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Blood Glucose ◽  
Embryonic Stem ◽  
Hypoglycemic Agents ◽  
Islet Cell Transplantation ◽  
High Blood Glucose ◽  
Glucose Levels ◽  
Chronic Hyperglycemia ◽  
Blood Glucose Levels

Diabetes mellitus (DM) is a group of metabolic diseases in which a person has high blood glucose levels resulting from defects in insulin secretion and insulin action. The chronic hyperglycemia damages the eyes, kidneys, nerves, heart, and blood vessels. Curative therapies mainly include diet, insulin, and oral hypoglycemic agents. However, these therapies fail to maintain blood glucose levels in the normal range all the time. Although pancreas or islet-cell transplantation achieves better glucose control, a major obstacle is the shortage of donor organs. Recently, research has focused on stem cells which can be classified into embryonic stem cells (ESCs) and tissue stem cells (TSCs) to generate functionalβcells. TSCs include the bone-marrow-, liver-, and pancreas-derived stem cells. In this review, we focus on treatment using bone marrow stem cells for type 1 and 2 DM.

scholarly journals The therapeutic effects of adipose-derived mesenchymal stem cells on obesity and its associated diseases in diet-induced obese mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hala jaber ◽  
Khodr Issa ◽  
Ali Eid ◽  
Fatima A. Saleh
Keyword(s):  
Stem Cells ◽  
Animal Model ◽  
Mesenchymal Stem Cells ◽  
Blood Glucose ◽  
Glucose Tolerance ◽  
Inflammatory Mediators ◽  
Atherogenic Index ◽  
Glucose Levels ◽  
Associated Diseases ◽  
Blood Glucose Levels

AbstractObesity is a global public health concern associated with increased risk of several comorbidities. Due to the limited effectiveness of current therapies, new treatment strategies are needed. Our aim was to examine the effect of adipose-derived mesenchymal stem cells (AD-MSCs) on obesity and its associated diseases in a diet-induced obese (DIO) animal model. C57BL6 mice were fed with either high fat diet (HFD) or CHOW diet for 15 weeks. Obese and lean mice were then subjected to two doses of AD-MSCs intraperitoneally. Mice body weight and composition; food intake; blood glucose levels; glycated hemoglobin (HbA1c), intraperitoneal glucose tolerance test and atherogenic index of plasma (AIP) were measured. Pro-inflammatory cytokines, tumor necrosis factor-α and interleukin-6, were also determined. AD-MSCs treatment reduced blood glucose levels, HbA1c and AIP as well as improved glucose tolerance in DIO mice. In addition, MSCs caused significant attenuation in the levels of inflammatory mediators in HFD-fed mice. Taken together, AD-MSCs were effective in treating obesity-associated diabetes in an animal model as well as protective against cardiovascular diseases as shown by AIP, which might be partly due to the attenuation of inflammatory mediators. Thus, AD-MSCs may offer a promising therapeutic potential in counteracting obesity-related diseases in patients.

scholarly journals Profil Antioksidan Darah Tikus Diabetes dengan Asupan Beras Merah yang Diperkaya Kappa-Karagenan dan Ekstrak Antosianin

2017 ◽  
Vol 37 (1) ◽  
pp. 82 ◽  
Author(s):  
Nurhidajah Nurhidajah ◽  
Mary Astuti ◽  
Sardjono Sardjono ◽  
Agnes Murdiati
Keyword(s):  
Blood Glucose ◽  
Diabetic Rats ◽  
Red Rice ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Reducing Ability ◽  
Male Wistar Rats ◽  
Kappa Carrageenan ◽  
Plasma Antioxidant

This study aimed to analyze the effect of red rice enriched-kappa-carrageenan and anthocyanin extracts on blood antioxidant profile in diabetic rats. Variables analyzed in this research were blood glucose, malondialdehyde (MDA) level, and plasma antioxidant by Ferric Reducing Ability of Plasma (FRAP) method. This study was conducted in vivo on male Wistar rats aged 2.5 months using completely randomized design. Rats divided into 6 groups based on types of feed, standard feed (normal and DM), red rice (BM), red rice enriched kappa-carrageenan (BMK), red rice enriched extracts of anthocyanin (BMA) and red rice enriched with kappa-carrageenan and extract anthocyanin (BMKA). Experiments were carried out for 6 weeks. Rats feed with red rice showed decreased in blood glucose levels from 234.26 to 84.78 mg/dL (p = 0.000), MDA diabetic group compared to BMKA 2.175 and 0.530 μmol/L (p = 0.000) respectively, and the rate of FRAP in DM and BMKA 69 and 216 nmol/mL (p = 0.000) respectively. This study showed that red rice enriched with kappa-carrageenan and anthocyanin extract was able to decrease blood glucose levels and increase plasma antioxidant of diabetic rats which characterized by decreased MDA value and increased FRAP value. ABSTRAKPenelitian ini bertujuan mengkaji pengaruh pemberian beras merah yang diperkaya kappa-karagenan dan ekstrak antosianin terhadap profil antioksidan darah pada tikus Diabetes Melitus (DM). Indikator penelitian adalah penurunan glukosa darah dan angka Malondialdehid (MDA) serta peningkatan antioksidan plasma dengan metode Ferric Reducing Ability of Plasma (FRAP). Penelitian ini dilakukan secara in vivo pada hewan coba tikus Wistar usia 2,5 bulan dengan desain penelitian rancangan acak lengkap (RAL). Tikus dibagi 6 kelompok pakan, yaitu standar negatif dan positif (normal dan DM), beras merah (BM), beras merah ditambah kappa-karagenan (BMK), beras merah ditambah ekstrak antosianin (BMA), dan beras merah ditambah kappa-karagenan dan ekstrak antosianin (BMKA). Percobaan dilakukan selama 6 minggu. Hasil penelitian menunjukkan bahwa kelompok BMKA setelah intervensi terjadi penurunan kadar glukosa darah dari 234,26 menjadi 84,78 mg/dL (p = 0,000), MDA kelompok DM dibandingkan BMKA masingmasing 2,175 dan 0,530 μmol/L (p = 0,000) serta FRAP pada kelompok DM dan BMKA masing-masing 69 dan 216 nmol/mL (p = 0,000). Kesimpulannya adalah beras merah dengan pengkayaan kappa-karagenan dan ekstrak antosianin mampu menurunkan kadar glukosa darah dan meningkatkan antioksidan plasma tikus diabetes yang ditandai dengan penurunan nilai MDA dan peningkatan nilai FRAP.

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