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Therapeutic Effects of Bone Marrow Stem Cells in Diabetic Rats

机译:骨髓干细胞对糖尿病大鼠的治疗作用

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Background: Currently, diabetes mellitus, specifically, Type 2 diabetes is a multifactorial metabolic disorder that affects more than 348 million people worldwide. It is considered to be one of the main causes of mortality. The pathway of type 2 diabetes is characterized both by insulin resistance in muscle, fat, and liver and a relative failure of the pancreatic β cell. Despite extensive study, yet no unifying hypothesis exists to explain these defects and the proper treatment. The key goal of diabetes treatment is to prevent complications because over time, diabetes can damage the heart, blood vessels, eyes, kidneys, and nerves. Therefore there is a great need to develop new and effective therapies for treating diabetic complications early before it cause irreparable tissue damage. Recently, advances experimental evidence empowers the idea that diabetic patients may greatly benefit from cell-based therapies, which include the use of adult stem and/or progenitor cells in disease therapy. In particular, therapeutic effect of bone marrow stem cell in treating the type 2 diabetic patients. Motivation: Mesenchymal stem cells (MSCs) are adherent and pluripotent and non-hematopoietic progenitor cells. Human bone marrow MSCs have been shown to inhibit antigen-dependent CD4+ and CD8+ T cell proliferation in an allogeneic setting in vitro. They have been found to reside in most organs and tissues investigated to date, including bone marrow, adipose, dermis, muscular tissue, hair follicles, the periodontal ligament and the placenta. In addition, recent studies have shown that adult bone marrow stem cells can differentiate into several types such as blood, liver, lung, skin, muscle, neuron and insulin producing cells. This has motivated us to explore potentials of their therapeutic applications in treating diabetes mellitus or type-2 diabetes. This article proposes a novel mechanism to isolate adult rat bone marrow stem cells and test their ability to treat diabetic rats. The main focus of this research is to investigate the therapeutic effect of mesenchymal stem cells on the diabetic rats. Experimental methods, data and results: The experimental studies were carried out based on twelveweek old healthy Sprague Dawley (S.D) rats and it was used for isolation and transplantation of stem cells. We carried a total number of 40 Sprague Dawley (S.D) male rats; 12-14 weeks old age and weighting 180-250 gm were used in the experimental study. Rats were obtained from Animal House of Nile Center for Experimental Researches, Mansoura, Egypt. Animals were housed in separate metal cages, fresh and clean drinking water was supplied adlibtium through specific nipple. The animals were anesthetized by halothane, and then the skin was sterilized with 70% ethyl alcohol before cutting the skin. The femurs and tibia were carefully dissected from adherent soft tissues. Then they were placed into sterilized beaker containing 70% ethyl alcohol for 1-2 min. The bones were put in Petri dish contain Phosphate buffer saline 1X (PBS) (Hyclone, USA) for wash. The bones were taken to laminar air flow (unilab biological safety cabinet class II, china) to extract the BM. The two ends of the bones were removed using sterile scissors. Conclusion and future work: Currently, the obtained results revealed that diabetes caused bad effects on the blood picture, pancreas and kidney functions, as well as the immune system represented by TNF. Treatment the diabetic rats by MSCs engrafting improved the tested parameters towards the stats of normal case. Nevertheless, the wide application of the stem cells engrafting still needs more investigations to be assured.
机译:背景:目前,糖尿病,特别是2型糖尿病是一种多因素代谢紊乱,影响全球超过3.48亿人。它被认为是导致死亡的主要原因之一。 2型糖尿病途径的特征在于肌肉,脂肪和肝脏的胰岛素抵抗以及胰腺β细胞的相对衰竭。尽管进行了广泛的研究,但尚无统一的假设来解释这些缺陷和适当的处理方法。糖尿病治疗的关键目标是预防并发症,因为随着时间的流逝,糖尿病会损害心脏,血管,眼睛,肾脏和神经。因此,迫切需要开发新的有效的治疗糖尿病并发症的早期方法,以免其造成无法修复的组织损伤。最近,先进的实验证据使糖尿病患者可能从基于细胞的治疗中受益匪浅,其中包括在疾病治疗中使用成体干细胞和/或祖细胞。尤其是骨髓干细胞在治疗2型糖尿病患者中的治疗作用。动机:间充质干细胞(MSCs)是粘附的,多能的和非造血祖细胞。已显示在体​​外同种异体环境中,人骨髓MSC可抑制抗原依赖性CD4 +和CD8 + T细胞增殖。迄今为止,它们已发现存在于大多数器官和组织中,包括骨髓,脂肪,真皮,肌肉组织,毛囊,牙周膜和胎盘。此外,最近的研究表明,成年骨髓干细胞可以分化为几种类型,例如血液,肝,肺,皮肤,肌肉,神经元和胰岛素产生细胞。这促使我们探索其在治疗糖尿病或2型糖尿病中的治疗应用潜力。本文提出了一种分离成年大鼠骨髓干细胞并测试其治疗糖尿病大鼠能力的新机制。这项研究的主要重点是研究间充质干细胞对糖尿病大鼠的治疗作用。实验方法,数据和结果:实验是在十二周龄健康Sprague Dawley(S.D)大鼠的基础上进行的,并将其用于干细胞的分离和移植。我们携带了40只Sprague Dawley(S.D)雄性大鼠;在实验研究中使用了12-14周龄,体重为180-250 gm。从埃及曼苏拉的尼罗河实验研究中心动物之家获得大鼠。将动物圈养在单独的金属笼中,通过特定的乳头提供新鲜和干净的饮用水。用氟烷将动物麻醉,然后在切割皮肤之前用70%乙醇对皮肤进行消毒。从附着的软组织上仔细解剖股骨和胫骨。然后将它们放入装有70%乙醇的无菌烧杯中1-2分钟。将骨头放入装有磷酸盐缓冲液1X(PBS)(Hyclone,USA)的培养皿中进行洗涤。将骨骼置于层流中(unilab生物安全柜II级,中国)以提取BM。用无菌剪刀除去骨头的两端。结论和今后的工作:目前,所获得的结果表明糖尿病对血象,胰腺和肾脏功能以及以TNF为代表的免疫系统造成了不良影响。通过MSCs移植治疗糖尿病大鼠,将测试参数提高至正常情况。然而,干细胞移植的广泛应用仍然需要更多的研究来确保。

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