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Fulltext Restoring the Angiogenic Capacity of the Human Diabetic Adipose-derived mesenchymal stem cells Primed with Deferoxamine as a Hypoxia Mimetic Agent: Role of HIF-1α

Tajali R, Eidi A, Ahmadi Tafti H, Pazouki A, Sharifi AM

Adv Pharm Bull, 2023 Mar;13(2):350-360.
PMID: 37342375 DOI: 10.34172/apb.2023.021

Purpose: Insufficient angiogenesis is associated with serious diabetic complications. Recently, adipose-derived mesenchymal stem cells (ADScs) are known to be a promising tool causing therapeutic neovascularization. However, the overall therapeutic efficacy of these cells is impaired by diabetes. This study aims to investigate whether in vitro pharmacological priming with deferoxamine, a hypoxia mimetic agent, could restore the angiogenic potential of diabetic human ADSCs. Methods: Diabetic human ADSCs were treated with deferoxamine and compared to normal and nontreated diabetic ADSCs for the expression of hypoxia inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2) and stromal cell-derived factor-1α (SDF-1α), at mRNA and protein levels, using qRT-PCR, western blotting and ELISA assay. Activities of matrix metalloproteinases (MMPs)-2 and -9 were measured using a gelatin zymography assay. Angiogenic potentials of conditioned media derived from normal, Deferoxamine treated, and non-treated ADSCs were determined by in vitro scratch assay and also three-dimensional tube formation assay. Results: It is demonstrated that deferoxamine (150 and 300 μM) stabilized HIF-1α in primed diabetic ADSCs. At the concentrations used, deferoxamine did not show any cytotoxic effects. In deferoxamine treated ADSCs, expression of VEGF, SDF-1α, FGF-2 and the activity of MMP-2 and MMP-9 were significantly increased compared to nontreated ADSCs. Moreover, deferoxamine increased the paracrine effects of diabetic ADSCs in promoting endothelial cell migration and tube formation. Conclusion: Deferoxamine might be an effective drug for pharmacological priming of diabetic ADSCs to enhance the expression of proangiogenic factors noted via HIF-1α accumulation. In addition, impaired angiogenic potential of conditioned medium derived from diabetic ADSCs was restored by deferoxamine.
Transplantation of adipose derived stem cells in diabetes mellitus; limitations and achievements

Tajali R, Eidi A, Tafti HA, Pazouki A, Kamarul T, Sharifi AM

J Diabetes Metab Disord, 2023 Dec;22(2):1039-1052.
PMID: 37975135 DOI: 10.1007/s40200-023-01280-8

OBJECTIVES: Diabetes mellitus (DM) is a complex metabolic disease that results from impaired insulin secreting pancreatic β-cells or insulin resistance. Although available medications help control the disease, patients suffer from its complications. Therefore, finding effective therapeutic approaches to treat DM is a priority. Adipose Derived Stem Cells (ADSCs) based therapy is a promising strategy in various regenerative medicine applications, but its systematic translational use is still somewhat out of reach. This review is aimed at clarifying achievements as well as challenges facing the application of ADSCs for the treatment of DM, with a special focus on the mechanisms involved.
METHODS: Literature searches were carried out on "Scopus", "PubMed" and "Google Scholar" up to September 2022 to find relevant articles in the English language for the scope of this review.
RESULTS: Recent evidence showed a significant role of ADSC therapies in DM by ameliorating insulin resistance and hyperglycemia, regulating hepatic glucose metabolism, promoting β cell function and regeneration, and functioning as a gene delivery tool. In addition, ADSCs could improve diabetic wound healing by promoting collagen deposition, inhibiting inflammation, and enhancing angiogenesis.
CONCLUSION: Overall, this literature review revealed the great clinical implications of ADSCs for translating into the clinical setting for the treatment of diabetes. However, further large-scale and controlled studies are needed to overcome challenges and confirm the safety and optimal therapeutic scheme before daily clinical application.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-023-01280-8.
Fulltext International survey on complications of religious fasting after metabolic and bariatric surgery

Kermansaravi M, Husain FA, Bashir A, Valizadeh R, Abbas SI, Abouzeid T, et al.

Sci Rep, 2023 Nov 18;13(1):20189.
PMID: 37980363 DOI: 10.1038/s41598-023-47673-w

Religious fasting in Ramadan the 9th month of the lunar year is one of five pillars in Islam and is practiced for a full month every year. There may be risks with fasting in patients with a history of metabolic/bariatric surgery (MBS). There is little published evidence on the possible complications during fasting and needs stronger recommendations and guidance to minimize them. An international survey was sent to surgeons to study the types of complications occurring during religious fasting in patients with history of MBS to evaluate the risk factors to manage and prepare more evidence-based recommendations. In total, 21 centers from 11 countries participated in this survey and reported a total of 132 patients with complications occurring during religious fasting after MBS. The mean age of patients with complications was 36.65 ± 3.48 years and mean BMI was 43.12 ± 6.86 kg/m2. Mean timing of complication occurring during fasting after MBS was 14.18 months. The most common complications were upper GI (gastrointestinal) symptoms including [gastroesophageal reflux disease (GERD), abdominal pain, and dyspepsia], marginal ulcers and dumping syndrome in 24% (32/132), 8.3% (11/132) and 23% (31/132) patients respectively. Surgical management was necessary in 4.5% of patients presenting with complications (6/132) patients due to perforated marginal or peptic ulcer in Single Anastomosis Duodenoileostomy with Sleeve gastrectomy (SADI-S), one anastomosis gastric bypass (OAGB) and sleeve gastrectomy (SG), obstruction at Jejunojenostomy after Roux-en-Y gastric bypass (RYGB) (1/6) and acute cholecystitis (1/6). Patients after MBS should be advised about the risks while fasting including abdominal pain, dehydration, and peptic ulcer disease exacerbation, and a thorough review of their medications is warranted to minimize complications.
Religious Fasting of Muslim Patients After Metabolic and Bariatric Surgery: a Modified Delphi Consensus

Kermansaravi M, Omar I, Mahawar K, Shahabi S, Bashir A, Haddad A, et al.

Obes Surg, 2021 Dec;31(12):5303-5311.
PMID: 34617207 DOI: 10.1007/s11695-021-05724-z

BACKGROUND: Fasting during Ramadan is one of the five pillars of the Muslim faith. Despite the positive effects of fasting on health, there are no guidelines or clear recommendations regarding fasting after metabolic/bariatric surgery (MBS). The current study reports the result of a modified Delphi consensus among expert metabolic/bariatric surgeons with experience in managing patients who fast after MBS.
METHODS: A committee of 61 well-known metabolic and bariatric surgeons from 24 countries was created to participate in the Delphi consensus. The committee voted on 45 statements regarding recommendations and controversies around fasting after MBS. An agreement/disagreement ≥ of 70.0% was regarded as consensus.
RESULTS: The experts reached a consensus on 40 out of 45 statements after two rounds of voting. One hundred percent of the experts believed that fasting needs special nutritional support in patients who underwent MBS. The decision regarding fasting must be coordinated among the surgeon, the nutritionist and the patient. At any time after MBS, 96.7% advised stopping fasting in the presence of persistent symptoms of intolerance. Seventy percent of the experts recommended delaying fasting after MBS for 6 to 12 months after combined and malabsorptive procedures according to the patient's situation and surgeon's experience, and 90.1% felt that proton pump inhibitors should be continued in patients who start fasting less than 6 months after MBS. There was consensus that fasting may help in weight loss, improvement/remission of non-alcoholic fatty liver disease, dyslipidemia, hypertension and type 2 diabetes mellitus among 88.5%, 90.2%, 88.5%, 85.2% and 85.2% of experts, respectively.
CONCLUSION: Experts voted and reached a consensus on 40 statements covering various aspects of fasting after MBS.
Metabolic and Bariatric Surgeon Criteria-An International Experts' Consensus

Kermansaravi M, Chiappetta S, Shikora SA, Musella M, Kow L, Aarts E, et al.

Obes Surg, 2024 Jul 24.
PMID: 39046625 DOI: 10.1007/s11695-024-07395-y

PURPOSE: With the global epidemic of obesity, the importance of metabolic and bariatric surgery (MBS) is greater than ever before. Performing these surgeries requires academic training and the completion of a dedicated fellowship training program. This study aimed to develop guidelines based on expert consensus using a modified Delphi method to create the criteria for metabolic and bariatric surgeons that must be mastered before obtaining privileges to perform MBS.
METHODS: Eighty-nine recognized MBS surgeons from 42 countries participated in the Modified Delphi consensus to vote on 30 statements in two rounds. An agreement/disagreement among ≥ 70.0% of the experts was regarded to indicate a consensus.
RESULTS: Consensus was reached on 29 out of 30 statements. Most experts agreed that before getting privileges to perform MBS, surgeons must hold a general surgery degree and complete or have completed a dedicated fellowship training program. The experts agreed that the learning curves for the various operative procedures are approximately 25-50 operations for the LSG, 50-75 for the OAGB, and 75-100 for the RYGB. 93.1% of experts agreed that MBS surgeons should diligently record patients' data in their National or Global database.
CONCLUSION: MBS surgeons should have a degree in general surgery and have been enrolled in a dedicated fellowship training program with a structured curriculum. The learning curve of MBS procedures is procedure dependent. MBS surgeons must demonstrate proficiency in managing postoperative complications, collaborate within a multidisciplinary team, commit to a minimum 2-year patient follow-up, and actively engage in national and international MBS societies.