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Neuropathy AND Diabetes AND Stem Cells

Haoyuan Li, Yanmin Zhang, Shangming Liu, Fengpeng Li, Benlin Wang, Jianjie Wang, Lanfang Cao, Tongliang Xia, Qingyu Yao, Haijun Chen, Yulin Zhang, Xiaodong Zhu, Yang Li, Gang Li, Jian Wang, Xingang Li, Shilei Ni
Dysfunction of neural stem cells (NSCs) has been linked to fetal neuropathy, one of the most devastating complications of gestational diabetes. Several studies have demonstrated that melatonin (Mel) exerted neuroprotective actions in various stresses. However, the role of autophagy and the involvement of Mel in NSCs in hyperglycemia (HG) have not yet been fully established. Here, we found that HG increased autophagy and autophagic flux of NSCs as evidenced by increasing LC3B II/I ratio, Beclin-1 expression, and autophagosomes...
January 14, 2019: Stem Cells
Hong Mao, Wei Wei, Xiu-Li Fu, Jing-Jian Dong, Xiao-Yu Lyu, Ting Jia, Yang Tang, Shi Zhao
BACKGROUND: Owing to the multifactorial nature of the pathogenesis of diabetic peripheral neuropathy (DPN), conventional drug therapies have not been effective. The application of stem cells transplantation may be useful for the treatment of DPN. This study was designed to assess the safety and therapeutic effects of autologous bone marrow mononuclear cells (BMMNCs) transplantation on the treatment of refractory DPN. METHODS: One hundred and sixty-eight patients with refractory DPN were recruited and enrolled in the study...
January 5, 2019: Chinese Medical Journal
Se Hee Min, Jung Hee Kim, Yu Mi Kang, Seung Hak Lee, Byung-Mo Oh, Kyou-Sup Han, Meihua Zhang, Hoe Suk Kim, Woo Kyung Moon, Hakmo Lee, Kyong Soo Park, Hye Seung Jung
Rodent stem cells demonstrated regenerative effects in diabetic neuropathy via improvement in nerve perfusion. As a pre-clinical step, we explored if human mobilized mononuclear cells (hMNC) would have the same effects in rats. hMNC were injected into Rt. hind-limb muscles of streptozotocin-induced diabetic nude rats, and the grafts were monitored using with MRI. After 4 weeks, the effects were compared with those in the vehicle-injected Lt. hind limbs. Nerve conduction, muscle perfusion and gene expression of sciatic nerves were assessed...
December 1, 2018: Journal of Endocrinology
Han Zhang, Xuqiang Nie, Xiujun Shi, Jiufeng Zhao, Yu Chen, Qiuyang Yao, Chengxin Sun, Jianwen Yang
Skin ulcers are a serious complication of diabetes. Diabetic patients suffer from vascular lesions and complications such as peripheral neuritis, peripheral vascular lesions, and collagen abnormalities, which result in skin wounds that are refractory and often develop into chronic ulcers. The healing of skin ulcers requires an inflammatory reaction, wound proliferation, remodeling regulation, and control of stem cells. Studies investigating diabetic cutaneous ulcers have focused on cellular and molecular levels...
2018: Frontiers in Pharmacology
Jiyin Zhou, Zuo Zhang, Guisheng Qian
Diabetes impairs the bone marrow (BM) architecture and function as well as the mobilization of immature cells into the bloodstream and number of potential regenerative cells. Circadian regulation of bone immature cell migration is regulated by β-adrenergic receptors, which are expressed on haematopoietic stem cells, mesenchymal stem cells, and osteoblasts in the BM. Diabetes is associated with a substantially lower number of sympathetic nerve terminal endings in the BM; thus, diabetic neuropathy plays a critical role in BM dysfunction...
October 5, 2018: Diabetes/metabolism Research and Reviews
Lidong Hu, Si-Cheng Dai, Xiaojun Luan, Jingsong Chen, Anthony Cannavicci
Diabetes mellitus (DM) is a chronic, multifactorial metabolic disease whereby insulin deficiency or resistance results in hyperglycemia. Endothelial cells (ECs) form the innermost layer of the blood vessel and produce and release a variety of vasoactive substances and growth factors to regulate vascular homeostasis and angiogenesis. Hyperglycemia and insulin resistance can cause endothelial dysfunction, leading to vascular complications such as coronary artery disease, peripheral arterial disease, diabetic nephropathy, neuropathy and retinopathy...
October 2018: Journal of Clinical Medicine Research
Stefania Niada, Chiara Giannasi, Alice Gualerzi, Giuseppe Banfi, Anna Teresa Brini
The adult stem cell secretome is currently under investigation as an alternative to cell-based therapy in regenerative medicine, thanks to the remarkable translational opportunity and the advantages in terms of handling and safety. In this perspective, we recently demonstrated the efficient performance of the adipose-derived mesenchymal stem/stromal cell (ASC) secretome in contrasting neuroinflammation in a murine model of diabetic neuropathy, where the administration of factors released by dermal fibroblasts (DFs) did not exert any effect...
2018: Stem Cells International
Bou-Yue Peng, Navneet Kumar Dubey, Viraj Krishna Mishra, Feng-Chou Tsai, Rajni Dubey, Win-Ping Deng, Hong-Jian Wei
High morbidity and mortality of diabetes mellitus (DM) throughout the human population is a serious threat which needs to be addressed cautiously. Type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) are most prevalent forms. Disruption in insulin regulation and resistance leads to increased formation and accumulation of advanced end products (AGEs), which further enhance oxidative and nitrosative stress leading to microvascular (retinopathy, neuropathy, and nephropathy) and macrovascular complications...
2018: Journal of Diabetes Research
Lara Lopes, Ocean Setia, Afsha Aurshina, Shirley Liu, Haidi Hu, Toshihiko Isaji, Haiyang Liu, Tun Wang, Shun Ono, Xiangjiang Guo, Bogdan Yatsula, Jianming Guo, Yongquan Gu, Tulio Navarro, Alan Dardik
BACKGROUND: Diabetic foot ulcer (DFU) is a severe complication of diabetes, preceding most diabetes-related amputations. DFUs require over US$9 billion for yearly treatment and are now a global public health issue. DFU occurs in the setting of ischemia, infection, neuropathy, and metabolic disorders that result in poor wound healing and poor treatment options. Recently, stem cell therapy has emerged as a new interventional strategy to treat DFU and appears to be safe and effective in both preclinical and clinical trials...
July 11, 2018: Stem Cell Research & Therapy
Afrânio Ferreira Evangelista, Marcos André Vannier-Santos, Gessica Sabrina de Assis Silva, Daniela Nascimento Silva, Paulo José Lima Juiz, Carolina Kymie Vasques Nonaka, Ricardo Ribeiro Dos Santos, Milena Botelho Pereira Soares, Cristiane Flora Villarreal
BACKGROUND: Diabetic neuropathy (DN) is a frequent and debilitating manifestation of diabetes mellitus, to which there are no effective therapeutic approaches. Mesenchymal stem/stromal cells (MSC) have a great potential for the treatment of this syndrome, possibly through regenerative actions on peripheral nerves. Here, we evaluated the therapeutic effects of MSC on spinal neuroinflammation, as well as on ultrastructural aspects of the peripheral nerve in DN-associated sensorial dysfunction...
June 22, 2018: Journal of Neuroinflammation
Tahir Farooq, Kanwal Rehman, Arruje Hameed, Muhammad Sajid Hamid Akash
Type 1 diabetes mellitus (T1DM) is classified as an autoimmune disease which progressively results in the depletion of insulin-secreting β-cells. Consequently, the insulin secretion stops leading to hyperglycemic situations within the body. Under severe conditions, it also causes multi-organ diabetes-associated dysfunctionalities notably hypercoagulability, neuropathy, nephropathy, retinopathy, and sometimes organ failures. The prevalence of this disease has been noticed about 3% that has highlighted the serious concerns for healthcare professionals around the globe...
June 13, 2018: Advances in Experimental Medicine and Biology
Wesley A Anderson, Alicia R Willenberg, Alexander J Bosak, Bradley J Willenberg, Stephen Lambert
BACKGROUND: Peripheral neuropathies affect approximately 20 million people in the United States and often stem from other chronic conditions, such as diabetes. In vitro methodologies to facilitate the understanding and treatment of these disorders often lack the cellular and functional complexity required to accurately model peripheral neuropathies. In particular, they are often 2D and fail to faithfully reproduce the 3D in vivo microenvironment. NEW METHOD: Embryonic dorsal root ganglion (DRG) explants were inserted into laminin derivatized capillary alginate gel (Capgel™), a bioabsorbable, self-assembling biomaterial, possessing parallel microchannel architecture, and cultured to mimic normal nerve development, including Schwann cell myelination...
July 15, 2018: Journal of Neuroscience Methods
Shaimaa A Abdelrahman, Mai A Samak, Sally M Shalaby
Being one of the most debilitating complications among diabetic patients, diabetic polyneuropathy (DPN) is a paramount point of continuous research. Stem cell therapies have shown promising results. However, limited cell survival and paracrine activities hinder its transfer from bench to bedside. We designed this study to evaluate fluoxetine-pretreatment technique of mesenchymal stem cells (MSCs) as an approach to enhance their paracrine and immunomodulatory properties in DPN. Effects of fluoxetine treatment of MSCs were tested in vitro...
October 2018: Cell and Tissue Research
Milton Packer
Drugs that inhibit dipeptidyl peptidase-4 (DPP-4) are conventionally regarded as incretin-based agents that signal through the glucagon-like peptide-1 (GLP-1) receptor. However, inhibition of DPP-4 also potentiates the stem cell chemokine, stromal cell-derived factor-1 (SDF-1), which can promote inflammation, proliferative responses and neovascularization. In large-scale cardiovascular outcome trials, enhanced GLP-1 signaling has reduced the risk of atherosclerotic ischemic events, potentially because GLP-1 retards the growth and increases the stability of atherosclerotic plaques...
January 8, 2018: Cardiovascular Diabetology
Jong Min Park, Sang Hwan Lee, Kwang Il Kim, Won Hee Kim, Joo Young Cho, Ki Baik Hahm, Sung Pyo Hong
BACKGROUND AND AIM: Diabetic gastropathy is associated with loss of interstitial cells of Cajal and autonomic neuropathy. Effective management for diabetic gastropathy is still unavailable. This study was aimed to confirm the pathogenetic changes in diabetic gastropathy and to examine the effect of treatment with placental-derived mesenchymal stem cells (PDMSCs) in stomachs of animal models. METHODS: Fourteen non-obese diabetic/ShiLtJ mice of 8 weeks were bled until week 30...
June 2018: Journal of Gastroenterology and Hepatology
Wei Liu, Fengchun Yu, Zhenghong Zhou, Yi-Chen Li, Dongsheng Fan, Kai Zhu
Diabetic neuropathy is one of the most common and serious complications of diabetes mellitus and metabolic syndrome. The current therapy strategies, including glucose control and pain management, are not effective for most patients. Growing evidence suggests that infiltration of inflammation factors and deficiency of local neurotrophic and angiogenic factors contribute significantly to the pathologies of diabetic neuropathy. Experimental and clinical studies have shown that bone marrow-derived stem cells (BMCs) therapy represents a novel and promising strategy for tissue repair through paracrine secretion of multiple cytokines, which has a potential to inhibit inflammation and promote angiogenesis and neurotrophy in diabetic neuropathy...
2017: BioMed Research International
Wu WenBo, Zhang Fei, Du YiHeng, Wang Wei, Yan TingMang, Zhou WenHao, Liu QianRu, Liu HaiTao
Diabetic cystopathy is a common complication of voiding disorders in diabetes mellitus. Neuropathy and bladder remodeling underlie the lack of efficacy of pharmacological and surgical treatments. Previous studies have shown that decreased levels of nerve growth factor (NGF) are closely associated with disease progression. Besides, application of human umbilical cord mesenchymal stem cells (hUC-MSCs) is also considered a promising therapeutic strategy for treatment of diabetic neuropathy. In our study, we determine the therapeutic efficacy and mechanisms of hUC-MSCs which transfected with NGF geen in ameliorating diabetic cystopathy for the first time...
December 2017: Neurochemical Research
Daphne P L Lin, Crispin R Dass
OBJECTIVES: Diabetes mellitus is often associated with a number of complications such as nephropathy, neuropathy, retinopathy and foot ulcers. However, weak bone is a diabetic complication that is often overlooked. Although the exact mechanism for weak bones within diabetes mellitus is unclear, studies have shown that the mechanism does differ in both type I (T1DM) and type II diabetes (T2DM). This review, however, investigates the application of mesenchymal stem cells, recombinant human bone morphogenetic protein-2, teriparatide, insulin administration and the effectiveness of a peroxisome proliferator-activated receptor-ϒ modulator, netoglitazone in the context of diabetic weak bones...
January 2018: Journal of Pharmacy and Pharmacology
Indrani Datta, Naini Bhadri, Pradnya Shahani, Debanjana Majumdar, Sowmithra Sowmithra, Rema Razdan, Ramesh Bhonde
Diabetic neuropathy (DN) is among the most debilitating complications of diabetes. Here, we investigated the effects of human dental pulp stem cell (DPSC) transplantation in Streptozotocin (STZ)-induced neuropathic rats. Six weeks after STZ injection, DPSCs were transplanted through two routes, intravenous (IV) or intramuscular (IM), in single or two repeat doses. Two weeks after transplantation, a significant improvement in hyperalgesia, grip-strength, motor coordination and nerve conduction velocity was observed in comparison with controls...
October 2017: Cytotherapy
Anna T Brini, Giada Amodeo, Lorena M Ferreira, Anna Milani, Stefania Niada, Giorgia Moschetti, Silvia Franchi, Elisa Borsani, Luigi F Rodella, Alberto E Panerai, Paola Sacerdote
Painful neuropathy is one of the complications of diabetes mellitus that adversely affects patients'quality of life. Pharmacological treatments are not fully satisfactory, and novel approaches needed. In a preclinical mouse model of diabetes the effect of both human mesenchymal stromal cells from adipose tissue (hASC) and their conditioned medium (hASC-CM) was evaluated. Diabetes was induced by streptozotocin. After neuropathic hypersensitivity was established, mice were intravenously injected with either 1 × 10(6) hASC or with CM derived from 2 × 10(6) hASC...
August 29, 2017: Scientific Reports
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