scholarly journals The Functionality of Endothelial-Colony-Forming Cells from Patients with Diabetes Mellitus

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1731
Author(s):  
Caomhán J. Lyons ◽  
Timothy O'Brien

Endothelial-colony-forming cells (ECFCs) are a population of progenitor cells which have demonstrated promising angiogenic potential both in vitro and in vivo. However, ECFCs from diabetic patients have been shown to be dysfunctional compared to ECFCs from healthy donors. Diabetes mellitus itself presents with many vascular co-morbidities and it has been hypothesized that ECFCs may be a potential cell therapy option to promote revascularisation in these disorders. While an allogeneic cell therapy approach would offer the potential of an ‘off the shelf’ therapeutic product, to date little research has been carried out on umbilical cord-ECFCs in diabetic models. Alternatively, autologous cell therapy using peripheral blood-ECFCs allows the development of a personalised therapeutic approach to medicine; however, autologous diabetic ECFCs are dysfunctional and need to be repaired so they can effectively treat diabetic co-morbidities. Many different groups have modified autologous diabetic ECFCs to improve their function using a variety of methods including pre-treatment with different factors or with genetic modification. While the in vitro and in vivo data from the literature is promising, no ECFC therapy has proceeded to clinical trials to date, indicating that more research is needed for a potential ECFC therapy in the future to treat diabetic complications.

2019 ◽  
Vol 28 (7) ◽  
pp. 967-972 ◽  
Author(s):  
Rachel Vanderschelden ◽  
Mayilone Sathialingam ◽  
Michael Alexander ◽  
Jonathan R. T. Lakey

The limited availability of human islets has led to the examination of porcine islets as a source of clinically suitable tissue for transplantation in patients with diabetes mellitus. Islets from porcine donors are commonly used in both in vitro and in vivo experiments studying diabetes mellitus. However, there are significant differences in quality and quantity of islet yield depending on donor pig age, as well as substantial differences in the costs of pancreas procurement in adult versus neonatal and juvenile pigs. In this study, we compared the total cost per islet of juvenile pig pancreata with that of neonatal and adult pigs. Although adult porcine pancreata yield, on average, more than five times the amount of islets than do juvenile and neonatal pancreata, we found that the high price of adult pigs led to the cost per islet being more than twice that of juvenile and neonatal islets (US $0.09 vs $0.04 and $0.02, respectively). In addition, neonatal and juvenile islets are advantageous in their scalability and retention of viability after culture. Our findings indicate that isolating neonatal and juvenile porcine islets is more cost-effective and scalable than isolating adult porcine islets.


1993 ◽  
Vol 70 (03) ◽  
pp. 389-392 ◽  
Author(s):  
Cristina R Falcon ◽  
Marco Cattaneo ◽  
Alberto Ghidoni ◽  
Pier Mannuccio Mannucci

SummaryPlatelets of patients with diabetes and no evidence of macroangiopathy produce normal amounts of thromboxane (Tx) B2 in vivo, whereas they usually show increased production in vitro. Since in vitro studies have been usually performed in citrated PRP, we tested the hypothesis that the discrepancy between in vivo and in vitro studies is due to the low concentration of plasma ionized calcium ([Ca 2+ ]o) that is present in citrated PRP. In fact, low [Ca 2+ ]o artifactually potentiates the platelet TxB2 production in vitro. Forty patients with diabetes mellitus and 37 matched Controls were studied. Blood was anticoagulated with citrate, the thrombin inhibitor D-phenylalanyl-l-prolyl-l-chloromethylketone (PPACK) or both anticoagulants. Platelet aggregation, release of 14C-serotonin and TxB2 production were induced in platelet rieh plasma (PRP) by several agonists. The following results were obtained: i) Citrated PRP: Arachidonic acid induced aggregation (p <0.01) and TxB2 production (p <0.02) were significantly greater in patients than in Controls. No statistically significant differences were found with other agonists. ii) PPACK PRP: No statistically significant difference was found between diabetic platelets and Controls, iii) PPACK plus citrate PRP: The results were not different from those obtained with citrate alone. Therefore, our results show that diabetic platelets produce normal amounts of TxB2 in vitro when the [Ca2+]o is physiological.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Serawit Deyno ◽  
Kassahun Eneyew ◽  
Sisay Seyfe ◽  
Elias Wondim

Abstract Background Despite tremendous developments in synthetic medicine, medicinal plants are still commonly used for the management of diabetes mellitus. This study synthesized scientific evidence on commonly used medicinal plants for the management of diabetes mellitus (DM) in Ethiopia. Methods Databases (PubMed, Cochrane, CINAHL and Google Scholar) have been thoroughly sought and evidence was synthesized. Results Thirty studies conducted anti-diabetic activities studies on 19 medicinal plants in Ethiopia. Most of the studies were in vivo studies (25). Others include; clinical study (1), in vitro studies (2), and both in vivo and in vitro study (2). Trigonella foenum-graecum L., clinical study, showed an improved lipid profile in type II diabetic patients. Comparable blood sugar level (BSL) lowering effect to glibenclimide was observed with Persea Americana and Moringa stenopetala. Noteworthy in vitro half maximal inhibitory concentration (IC 50) of Aloe megalacantha B and Aloe monticola R were observed. Animal model studies demonstrated the relative safety of the plants extract and phytochemistry studies showed various components. Conclusion Medicinal plants used for management of diabetes mellitus in Ethiopia are worthy for further study for pharmacologically active ingredients and clinical evaluation.


2020 ◽  
Vol 11 (SPL4) ◽  
pp. 1130-1139
Author(s):  
Syed Sagheer Ahmed ◽  
Rupesh Kumar M ◽  
Rajesh Kowti ◽  
Ramesh B

The global prevalence of diabetes mellitus is increasing day by day. Despite using synthetic anti-diabetic agents, diabetic patients must modify their lifestyle, including routine diet. Vegetables are the adequate source of vitamins, dietary fibres, minerals and Phytoconstituents. Use of vegetables is growing among the people as a part of the diet. They, with their antioxidant properties, can maintain good health and reduce the risk of chronic diseases. Besides, they contain many dietary fibres that are anti-diabetic. The constituents present in these vegetables help to reduce blood glucose level through several mechanisms such as alpha-amylase and alpha-glucosidase enzyme inhibition, Dipeptidyl peptidase IV (DPP IV) inhibition, enhancing the expression of peroxisome proliferator activator receptor gamma (PPAR) γ and glucose transporter 4 (GLUT4). Therefore the people must consume such vegetables with the proper knowledge to control diabetes mellitus and its complications. Hence the present review focuses on summarizing in vitro and in vivo  anti-diabetic activity of most common dietary vegetables.


2017 ◽  
Vol 4 (5) ◽  
pp. 1378
Author(s):  
Amrut Kumar Mohapatra ◽  
Pratima Singh ◽  
Saswat Subhankar

Background: Onset of tuberculosis is high among diabetic mellitus patients in relation to non-diabetic patients. Due to weakened immune system there is a greater risk of tuberculosis seen among type 2 diabetes mellitus patients. As a result, affected patients have difficulty in responding to any kind of treatment when compared to healthy individuals. The objective was to study the clinical and radiological profile of pulmonary tuberculosis among patients having diabetes mellitus (DM).Methods: The study was conducted at the department of pulmonary medicine, in a tertiary health care centre in Eastern India. The study included smear positive pulmonary tuberculosis (PTB) patients with diabetes mellitus and the patients who were smear positive for pulmonary tuberculosis (control group) who met the criteria to participate in the study after a thorough examination. Informed written consent was obtained from all patients before enrolment.Results: A total of 80 patients (15 to 65 years and above) were enrolled in the study with equal numbers being diagnosed with diabetes who had elevated blood sugar values (refer to Table 1). Classical clinical signs were totally correlated with radiography and 57.5% cases showed pulmonary lesions. Among the radiological findings, infiltration was most common in both groups, but more significant in PTB DM group (75 %) followed by cavity (52.5%) in PTB DM group.Conclusions: It can be concluded from the study that in diabetic patients the pattern of pulmonary tuberculosis was significantly different from non-diabetic patients. Pre-treatment bacillary load was high in diabetic patients with pulmonary tuberculosis.


1977 ◽  
Author(s):  
R. Giustolisi ◽  
R. Musso ◽  
T. Lombardo ◽  
M. Russoand ◽  
E. Cacciola

Some coagulation aspects are studied in diabetes mellitus because this dismetabo-lic disease represents a “high risk factor” of predisposition leading to classical lesions of the vascular wall and thrombosis. Were studied 24 diabetic patients between 16 and 68 years old and 14 healthy subjects. Tests performed are followed: partial thromboplastyn time(PTT), plasma coagulation time RVV(RVV-T), antithrombin III(At-III), alpha2macroglobulin(a2M), fibrin/fibrinogen degradation products(FDP), ethanol gelation(EG) and protamine sulphate(PS), euglobulin lysis time(ELT), platelet adhesiveness to glass(PAG), platelet adhesiveness in vivo (PAV), platelet factor-3 availability(PF-3), platelet aggregation by ristocetin 1, 2-1, 5-1, 8 mg/ml(RIPA),Diabetics showed a fall in At-III, increase a2M, a significant decrease ELT and increase FDP with often positivity EG. We also noted a shortening of PTT, PF-3 rate and RVV-T. In vitro platelets adhesiveness rises more than it does in vivo. Besides the PPP from diabetics increased the control subjects PAG. The RIPA is increased. Our findings showed, therefore, in diabetic patients a thrombophilic pattern by blood hypercoagulability and fibrinolytic activity decreased.


1979 ◽  
Author(s):  
L.C. Best ◽  
M.B. McGuire ◽  
J.D. Ward ◽  
T. Holland ◽  
F. E. Preston ◽  
...  

Platelets from diabetics with microvascular complications were shown to have lowered aggregation thresholds to ADP, epinephrine and collagen. They also produced more malonyl dialdehyde (MDA) than normal controls. In eight diabetic subjects, administration of dipyridamole (100mg tds)raised platelet aggregation thresholds and increased cyclic AMP levels, presumably as a result of inhibition of phosphodiesterase activity. It also caused a slight reduction of MDA production. This latter effect could be due to the rise in cyclic AMP, although we have found an apparently direct inhibitory effect to dipyridamole on MDA and thromboxane B2 production by intact platelets and platelet microsomes in vitro. On withdrawal of the drug, platelet cyclic AMP and MDA levels and aggregation thresholds returned toward pre-treatment levels. The administration of aspirin (120) plus dipyridamole markedly inhibited platelet aggregation, particularly in response to arachidonic acid and collagen and strongly inhibited MDA production. However, the rise in platelet cyclic AMP levels produced by dipyridamole alone was not present when aspirin and dipyridamole were given together, Aspirin may influence platelet cyclic AMP metabolism directly or by inhibiting prostacyclin formation. Thus, under appropriate conditions, basal platelet cyclic AMP may provide an index of PGI2 production in vivo.


2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Adriana Machado-Lima ◽  
Erika R Oliveira ◽  
Rodrigo T Iborra ◽  
Gabriela Castilho ◽  
Edna R Nakandakare ◽  
...  

Advanced glycation end products (AGE) are elevated in diabetes mellitus (DM) and predict the development of atherosclerosis. In vitro produced AGE-albumin induces oxidative stress that is linked to the reduction in ABCA-1 levels and cholesterol efflux mediated by apo A-I and HDL-subfractions, leading to macrophage cholesterol accumulation. We characterized the glycation level/profile of human serum albumin (HSA) isolated by fast protein liquid chromatography from poorly controlled type 1 (DM1) and type 2 (DM2) diabetes mellitus patients (HbA1c > 8%) in comparison to control (C) individuals, and how these AGE-albumin can interfere in macrophage lipid accumulation. The glycation level of HSA from C, DM1 and DM2 was analyzed by MALDI mass spectrometry and was similar between DM1 and DM2-HSA. An increased mean mass was observed in DM1-HSA (68,544 ± 192 Da; n=6) and DM2-HSA (68,547 ± 132 Da; n=6) compared to C-HSA (67,846 ± 301 Da; n=6), reflecting the condensation of at least 8 and 5 units of glucose, respectively. The tryptic digestion of C-HSA generated a number of peptide species higher than those originated from DM1 and DM2-HSA. Macrophages isolated from peritoneal wild-type mice were treated for 18 h with C, DM1 or DM2-HSA in order to measure the 14C-cholesterol efflux and the mRNA expression of NOX-4 (NADPHoxidase4), ABCA-1 (Abca1) and ABCG-1 (Abcg1). Data were compared by one-way ANOVA and Dunnet′s post test. In comparison to cells treated with C-HSA the expression of NADPHoxidase4 (p<0.05; n=3) mRNA was increased after cell treatment with DM1 (3.2x) and DM2-HSA (0.7x), confirming oxidative stress. Abcg1 mRNA was reduced by DM2-HSA (26%; p<0.05; n=3); Abca1 mRNA was unchanged but ABCA-1 protein content was greatly reduced (82 and 25%, respectively in DM1 and DM2-HAS; p<0.05; n=12). The % of apo A-I mediated cholesterol efflux was impaired in DM1 (1.3 ± 0.3) and DM2-HSA-treated cells (2.4 ± 0.5) as compared to C-HSA (4.4 ± 0.5; n= 5; p<0.05). The level of advanced glycation that takes place in vivo was similar between DM1 and DM2-HSA and induced macrophage oxidative stress and impairment in cholesterol efflux that may contribute to atherogenesis in DM. Funding: FAPESP, Brazil (2012/19112-0)


2012 ◽  
Vol 58 (6) ◽  
pp. 727-736 ◽  
Author(s):  
V.Z. Lankin ◽  
G.G. Konovalova ◽  
A.K. Tikhaze ◽  
L.V. Nedosugova

Natural dicarbonyls, which may be accumulated during oxidative stress in atherosclerosis (e.g. malondialdehyde) or carbonyl stress in diabetes mellitus (glyoxal and methylglyoxal) effectively inhibited the activities of commercial preparations of antioxidant enzymes: catalase, Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and Se-contained glutathione peroxidase from human and bovine erythrocytes and also rat liver glutathione-S-transferase. After incubation of human erythrocytes with 10 mM of each investigated dicarbonyls the decrease of intracellular Cu,Zn-SOD was observed. The decreased activity of erythrocyte Cu,Zn-SOD was also detected in diabetic patients with carbohydrate metabolism disturbance but effective sugar-lowered therapy was accompanied by the increase of this enzyme activity. The increase of erythrocytes activity of Cu,Zn-SOD of diabetic patients theated with metformin (which may utilize methylglyoxal) was higher than in erythrocytase of diabetic patients subjected to traditional therapy.


Blood ◽  
1996 ◽  
Vol 87 (6) ◽  
pp. 2195-2204 ◽  
Author(s):  
S Slavin ◽  
E Naparstek ◽  
A Nagler ◽  
A Ackerstein ◽  
S Samuel ◽  
...  

Allogeneic bone marrow transplantation (BMT) is the only effective treatment for hematologic malignancies resistant to conventional chemotherapy. Until recently, no cure existed for patients who relapsed post-BMT. We present our long-term observations on remission induction, after relapse post-BMT, by allogeneic cell therapy (allo-CT) and the feasibility of remission induction in allo-CT-resistant patients by activation of antileukemia effector cells with recombinant human interleukin-2 (rhIL-2) in vitro and in vivo. The longest observation of successful allo-CT (event-free survival, greater than 8 years) was made in a patient with resistant pre-B lymphoblastic leukemia who received infusions with graded increments of donor (female) peripheral blood lymphocytes (PBL) as soon as bulky hematologic and extramedullary relapse was noticed early post-BMT. The patient is currently without evidence of residual host (male) cells as determined by polymerase chain reaction (PCR). Of 17 patients with acute and chronic leukemia in relapse after BMT, 10 were reinduced into complete remission. Four patients with cytogenetic relapse responded to allo-CT alone, while five of six patients with overt hematologic relapse responded only after additional activation of donor with rhIL-2. Allo-CT can, therefore, successfully reverse chemoradiotherapy-resistant relapse of both acute and chronic leukemia. Moreover, in patients resistant to donor lymphocyte infusion, remission can be accomplished by additionally activating donor PBL in vitro and/or in vivo with rhIL-2. Based on our observations, after BMT, allo-CT should be considered the treatment of choice for patients with hematologic malignancies resistant to conventional anticancer modalities. Allogeneic activated cell therapy (allo ACT) should be considered for patients with tumor cells resistant to allo-CT. Although allo-CT, followed if indicated by allo-ACT, can be effective for patients with overt hematologic relapse, reversal of persistent minimal residual disease or documented molecular/cytogenetic relapse early after BMT may also be considered as a possible indication for allo-CT.


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