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Treating Parkinson Disease with Autologous Telomerase-Positive Stem Cells, Update 2021 自体端粒酶阳性干细胞治疗帕金森病,更新2021
Pub Date : 2021-06-30 DOI: 10.33425/2639-9512.1059
H. Young, M. Speight
Parkinson disease (PD) is the second most common progressive neurodegenerative disorder that affects older adults. PD is characterized by a low level of dopamine being expressed in the striatum and a deterioration of dopaminergic neurons and associated neural networks in the substantia nigra of the midbrain. Current medical, surgical, and rehabilitative treatments for PD have long-term side effects and do not halt the progression of the disease. Stem cell therapies generating dopaminergic neurons from fetal brain tissue, human embryonic stem cells, human induced pluripotent stem cells, mesenchymal stem cells, human neural stem cells, direct reprogramming of somatic cells and direct reprogramming of stem cells by either gene editing, and/or gene transfer have elicited keen interest as to eventual therapeutics for Parkinson disease. Unfortunately, thus far, these experimental therapies have proved to be of limited therapeutic value in clinical trials. Using a neurotoxin-induced animal model of PD, transplantation of a naïve telomerase positive pluripotent stem cell clone demonstrated reconstitution of dopaminergic neurons and associated neural networks when stereotactically injected into neurotoxin-lesioned substantia nigra pars compactum of the ventral midbrain. Two IRB-approved clinical trials in small cohort studies (n=8 & n=4), with a combined sample size of n=12, demonstrated that intranasal infusion of autologous telomerase positive totipotent cells followed by intravenous infusion of telomerase positive pluripotent stem cells and mesodermal stem cells had a positive influence on patient symptomology with Parkinson’s Disease. No adverse effects were reported by any participant or their respective caregiver for the entire combined small cohort study (n=12). Taken together as a 2021 update of this on-going clinical study, 33% (n=4) showed moderate to no benefit of telomerase positive stem cell treatment by demonstrating a continued decline in symptoms after treatment; 33% (n=4) remained in stasis after the first month after treatment; and 33% (n=4) resolved their symptoms. The results suggest that autologous telomerase positive stem cells, TSCs, PSCs, and MesoSCs, are safe and efficacious (66%) to reduce the symptoms in participants with Parkinson’s disease.
帕金森病(PD)是影响老年人的第二常见的进行性神经退行性疾病。PD的特点是纹状体中多巴胺表达水平低,中脑黑质中多巴胺能神经元和相关神经网络退化。目前PD的医学、外科和康复治疗有长期的副作用,并不能阻止疾病的进展。从胎儿脑组织、人类胚胎干细胞、人类诱导多能干细胞、间充质干细胞、人类神经干细胞、通过基因编辑和/或基因转移直接重编程体细胞和直接重编程干细胞中产生多巴胺能神经元的干细胞疗法,引起了人们对帕金森病最终治疗方法的浓厚兴趣。不幸的是,到目前为止,这些实验性疗法在临床试验中被证明是有限的治疗价值。在神经毒素诱导的帕金森病动物模型中,将naïve端粒酶阳性多能干细胞克隆移植到神经毒素损伤的中脑腹侧致密黑质中,显示出多巴胺能神经元和相关神经网络的重建。两项经irb批准的小队列临床试验(n=8和n=4),总样本量为n=12,证明鼻内输注自体端粒酶阳性的全能细胞,然后静脉输注端粒酶阳性的多能干细胞和中胚层干细胞对帕金森病患者的症状有积极影响。在整个联合小队列研究(n=12)中,没有任何参与者或他们各自的护理人员报告不良反应。作为这项正在进行的临床研究的2021年更新,33% (n=4)的患者在治疗后症状持续下降,显示端粒酶阳性干细胞治疗的中度至无益处;33% (n=4)患者在治疗后1个月仍处于停滞状态;33% (n=4)的患者症状得到缓解。结果表明,自体端粒酶阳性干细胞,TSCs, PSCs和MesoSCs,在减轻帕金森病患者症状方面是安全有效的(66%)。
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引用次数: 6
Alzheimer’s Disease Treated with Autologous and Allogeneic TelomerasePositive Stem Cells 自体和异体端粒酶阳性干细胞治疗阿尔茨海默病
Pub Date : 2021-06-30 DOI: 10.33425/2639-9512.1058
H. Young, M. Speight
Alzheimer’s disease is an insidious and progressive loss of balance and cognitive memories from present time to distant past that occurs in reverse chronological order. While the cause for AD is poorly understood, the presence of tau, aggregation of beta-amyloid protein, activated microglia, and massive losses of neurons and their synaptic processes have been associated with the disease. Genetics appear to play a major role in AD, but comorbidities intervene as well. There are five drug treatments approved to control the symptoms of the disease, but none were clinically proven to alter the course or decrease the risk for AD. Death eventually occurs, usually 3-9 years after initial diagnosis. Stem cells, e.g., embryonic stem cells, induced pluripotent stem cells; mesenchymal stem cells, medicinal signaling cells, and neural stem cells have been suggested as potential treatments for AD. While clinical trials demonstrated safety of administering some of these stem cells, none demonstrated any efficacy for reversing the symptoms of AD. We report the use of adult telomerase positive stem cells as a treatment modality for reversing the symptoms of AD. In a small cohort clinical trial (n=4), there were no adverse reactions reported for any individual treated. In addition, efficacy for telomerase positive stem cells approximated 50% for reduction in symptoms of Alzheimer’s disease up to four months after their last telomerase positive stem cell treatment.
阿尔茨海默病是一种从现在到遥远的过去以相反的时间顺序发生的平衡和认知记忆的逐渐丧失。虽然阿尔茨海默病的病因尚不清楚,但tau蛋白的存在、β -淀粉样蛋白的聚集、激活的小胶质细胞以及神经元及其突触过程的大量损失与该疾病有关。基因似乎在阿尔茨海默病中起主要作用,但合并症也会起作用。目前已有五种药物被批准用于控制阿尔茨海默病的症状,但没有一种药物被临床证明可以改变病程或降低患阿尔茨海默病的风险。通常在初次诊断后3-9年死亡。干细胞,如胚胎干细胞、诱导多能干细胞;间充质干细胞、药物信号细胞和神经干细胞被认为是阿尔茨海默病的潜在治疗方法。虽然临床试验证明了使用这些干细胞的安全性,但没有一项试验证明对逆转阿尔茨海默病的症状有任何疗效。我们报告使用成人端粒酶阳性干细胞作为逆转AD症状的治疗方式。在一项小型队列临床试验(n=4)中,未报告任何接受治疗的个体出现不良反应。此外,端粒酶阳性干细胞在最后一次端粒酶阳性干细胞治疗4个月后,阿尔茨海默病症状的减轻效果约为50%。
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引用次数: 1
Blunt Force Trauma-Induced Total Bilateral Visual Impairment of 13 Years Duration Treated with Autologous Telomerase-Positive Stem Cells 自体端粒酶阳性干细胞治疗13年钝性创伤性双侧全视力障碍
Pub Date : 2021-06-30 DOI: 10.33425/2639-9512.1063
H. Young, M. Speight
Loss of visual acuity may result from genetics, cancer, metabolic disorders, trauma, or aging. Adult telomerase- positive totipotent stem cells have been identified in multiple species of animals, including humans. Characterization studies to identify differentiated cells utilized three clones of adult-derived totipotent stem cells (TSCs) and treated them with induction factors consisting of chemical mediators, human recombinant proteins and cell-specific exosomes. Results demonstrated that the TSC clones would form cells expressing phenotypic markers of the neural ectodermal lineage, e.g., ectodermal stem cells, ectodermal progenitor stem cells, neurons, ganglion cells, glial cells, and neural crest derivatives. Autologous TSCs were shown to partially restore function in clinical trial participants with Alzheimer’s disease, Parkinson’s disease, and Age-related Dry Macular Degeneration. It was hypothesized that following intranasal infusion, TSCs would migrate to areas associated with the visual pathway to repair and/or regenerate damaged and/or missing cells, thus restoring function. In this small cohort study (n=1), the presenting symptom for a 17-year-old female was total bilateral visual impairment (complete blindness) of 13-years duration, due to severe head trauma from an automobile accident at four years of age. Following her first TSC treatment, she could see indistinct black shapes on a background of a dark shade of gray. Following her second TSC treatment she could see background as a lighter shade of gray and a black square with slightly more distinct borders. No adverse effects were noted after either autologous TSC treatment. These results suggest that two treatments with TSCs were both safe and somewhat efficacious in helping to partially restore her ‘night’ vision.
视力的丧失可能是由遗传、癌症、代谢紊乱、创伤或衰老造成的。成人端粒酶阳性的全能干细胞已经在包括人类在内的多种动物中被鉴定出来。鉴定分化细胞的特性研究使用了3个成人来源的全能干细胞(TSCs)克隆,并用由化学介质、人重组蛋白和细胞特异性外泌体组成的诱导因子对其进行处理。结果表明,TSC克隆可形成表达神经外胚层谱系表型标记的细胞,如外胚层干细胞、外胚层祖干细胞、神经元、神经节细胞、胶质细胞和神经嵴衍生物。在阿尔茨海默病、帕金森病和年龄相关性干性黄斑变性患者的临床试验中,自体TSCs被证明可以部分恢复功能。据推测,鼻内输注后,TSCs会迁移到与视觉通路相关的区域,修复和/或再生受损和/或缺失的细胞,从而恢复功能。在这项小型队列研究中(n=1),一名17岁女性的主要症状是持续13年的完全双侧视力障碍(完全失明),原因是4岁时车祸造成的严重头部创伤。在她第一次接受TSC治疗后,她可以在深灰色的背景上看到模糊的黑色形状。在她的第二次TSC处理之后,她可以看到背景是浅灰色和一个黑色的正方形,边缘稍微清晰一些。两种自体TSC治疗均无不良反应。这些结果表明,两种使用tsc的治疗方法在帮助部分恢复她的“夜间”视力方面既安全又有效。
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引用次数: 4
Capparis Spinosa is an Alternative Drug for Vitality Capparis Spinosa是一种活力的替代药物
Pub Date : 2021-06-30 DOI: 10.33425/2639-9512.1060
Ali Awad Hamoud Aljeboory, Rafid Mohammed Mohammed Hashim, Yahya Yahya Zaki Farid
From traditional and folk medicine, the fruit of Capparis used as antiseptic for intestinal dysentery and as protective for the liver from diseases in addition it is used as aphrodisiac and antihypertensive agent in addition as anticancer so as we know that natural product still a bank of new drug resources for the following reasons; these are a target for production by biotechnology. In addition, they are as a source of new lead compounds of novel chemical structure, which act as a tool for invention of new drug using nanoscince in medicine. There is a third reason as active ingredients of useful treatment divided from traditional medicine. As we know the drugs which manufacturing from bioactive, materials are cheap and available and not polluted as the chemical synthetic drugs and do not need-sophisticated technology. In this study we use fruits and leaves of Capparis dried and milled then extracted with alcohol 80% in addition deal with different organic solvent and get rid of chlorophyll and caryophilline and phytochemical studies by using liquid-liquid HPLC and we managed to extract quercitin and quercitrin in addition to proteins. The last product was anti-oxidant compared with racemic vitamin C using Noradrenaline as a test for the oxidation. Lastly, we see the activity of these materials as potent activator to the male compared with Sildenafil. The Capparis increase the activity twice the effect of sildenafil, And Tadalafil.
从传统和民间医学上看,枸杞的果实被用作肠道痢疾的防腐剂,保护肝脏免受疾病的侵害,还被用作壮阳药和降压药,还有抗癌的作用,所以我们知道它是一种天然产物,也是一种新药资源库,原因如下:这些都是生物技术生产的目标。此外,它们还作为新化学结构的新先导化合物的来源,作为利用纳米科学在医学上发明新药的工具。第三个原因是有效治疗成分与传统药物的区别。正如我们所知,从生物活性物质中制造的药物,材料便宜,易得,不像化学合成药物那样污染严重,不需要复杂的技术。本研究以红辣椒果实和叶片为原料,经干燥、研磨后80%乙醇提取,并对不同的有机溶剂进行处理,去除叶绿素和核桃碱,采用液-液高效液相色谱法进行植物化学研究,除提取蛋白质外,还提取出槲皮素和槲皮苷。最后一种产品与消旋维生素C进行了抗氧化比较,用去甲肾上腺素作为氧化试验。最后,与西地那非相比,我们看到这些物质的活性对男性来说是有效的激活剂。Capparis增加的活性是西地那非和他达拉非的两倍。
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引用次数: 0
Traumatic Spinal Cord Injury at T12 Causing Complete Paraplegia for 12-Years Duration Treated with Autologous Telomerase Positive Stem Cells 自体端粒酶阳性干细胞治疗创伤性脊髓损伤致12年完全截瘫
Pub Date : 2021-06-30 DOI: 10.33425/2639-9512.1061
H. Young, M. Speight
A 36-year-old paraplegic female presented to the clinic for bi-monthly pain management below thoracic level, T12. She was absent of cutaneous sensation below level of T12, absent of bladder/rectum function, absent genital function, and could not move around without the use of a wheelchair. She displayed anxiety, depression, and decreased feeling of self-worth. Her intense pain was due to a traumatic spinal cord crush injury from a car accident 12 years previously. To date, no effective pharmacological or regenerative treatment has been developed to treat chronic spinal cord injuries. Advances in stem cell technologies (e.g., embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), neural stem cells (NSCs), NSCs induced from either iPSCs or ESCs, mesenchymal stem cells, medicinal signaling cells, etc.), biomaterials, immune engineering, and nanotechnologies have been applied to regenerative therapies following subacute spinal cord injuries. Although these therapies have proven safe for subacute spinal cord injury in animal models, their efficacy in clinical trials to date has not been demonstrated. The participant was presented with opportunity to join a clinical trial using autologous adult-derived telomerase positive stem cells for amelioration of her neurogenic problems. She agreed to the trial because she wanted to walk. Her first autologous stem cell transplant did not ameliorate any of her symptoms. In retrospect, this was due to the anesthetic having a 100% kill ratio for telomerase positive stem cells. Switching to an anesthetic with a 0% kill ratio allowed the telomerase positive stem cells the potential to restore neurogenic function as previously noted for Parkinson disease, age-related dry macular degeneration, and Alzheimer’s disease. Following two telomerase positive stem cell treatments there was restoration of sensation from below her umbilicus to just proximal to her knee joints and restoration of function of her urinary bladder and rectum. Due to the limited time frame following her treatments (e.g., four months), no sustained voluntary control was seen in the musculature of her lower extremities. Her inability to walk following two telomerase positive stem cell treatments prompted her to drop out of the study. Due to restoration of function to damaged structures of the central and peripheral nervous system after following telomerase positive stem cell transplants in this chronic spinal cord injured patient, suggest that TSCs, PSCs, and MesoSCs might have been involved in this restorative process. Since no adverse events were reported during her study, autologous telomerase positive stem cells appeared to be safe for administration. And with restoration of the neurogenic activities during the limited time frame of treatment, administration of telomerase positive stem cells appears to be efficacious in their activities to restore neurogenic function to the tissues absent of those activities for 12 years duration.
一名36岁截瘫女性因胸椎T12以下疼痛治疗每月两次到诊所就诊。患者T12以下皮肤感觉缺失,膀胱/直肠功能缺失,生殖功能缺失,不借助轮椅不能活动。她表现出焦虑、抑郁和自我价值感的下降。她剧烈的疼痛是由于12年前的一次车祸造成的创伤性脊髓挤压伤。到目前为止,还没有有效的药物或再生治疗方法来治疗慢性脊髓损伤。干细胞技术(如胚胎干细胞(ESCs)、诱导多能干细胞(iPSCs)、神经干细胞(NSCs)、由iPSCs或ESCs诱导的NSCs、间充质干细胞、药物信号细胞等)、生物材料、免疫工程和纳米技术的进展已被应用于亚急性脊髓损伤后的再生治疗。尽管这些疗法在动物模型中已被证明对亚急性脊髓损伤是安全的,但迄今为止,它们在临床试验中的有效性尚未得到证实。该参与者有机会加入一项临床试验,使用自体成人来源的端粒酶阳性干细胞来改善她的神经源性问题。她同意接受审判,因为她想无罪释放。她的第一次自体干细胞移植没有改善她的任何症状。回想起来,这是因为麻醉剂对端粒酶阳性的干细胞有100%的杀伤率。切换到0%杀伤率的麻醉剂后,端粒酶阳性的干细胞有可能恢复神经原性功能,就像之前提到的帕金森病、年龄相关性干性黄斑变性和阿尔茨海默病一样。经过两次端粒酶阳性干细胞治疗后,她的感觉从脐以下恢复到膝关节近端,膀胱和直肠功能恢复。由于治疗后时间有限(如4个月),其下肢肌肉组织未见持续的自主控制。她在两次端粒酶阳性干细胞治疗后无法行走,这促使她退出了这项研究。由于该慢性脊髓损伤患者端粒酶阳性干细胞移植后中枢和周围神经系统受损结构的功能恢复,提示TSCs、PSCs和MesoSCs可能参与了这一恢复过程。由于在她的研究中没有报告不良事件,自体端粒酶阳性干细胞似乎是安全的。在有限的治疗时间内,端粒酶阳性干细胞似乎可以有效地恢复那些在12年内没有这些活动的组织的神经发生功能。
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引用次数: 0
The Mechanoadaptation Concept of Cells 细胞的机械适应概念
Pub Date : 2021-05-18 DOI: 10.3233/BHR210010
J. Stoltz, Y. Rémond, D. George, J. Magdalou, Yueying Li, Zhongchao Han, Lei Zhang, N. Isla, Yun Chen
Almost all cells in the human body are subjected to mechanical stresses. These forces can vary from a few Pascals (shear stress) to some mega Pascals (on hip cartilage). It is now well known that mechanical forces have a decisive effect on cellular physiology. In 1880, W. Roux introduced the concept of functional adaptation; which can be defined as a quantitative autoregulation controlled by stimuli like mechanical forces. These stresses influence functionality and cellular metabolism and can lead to appropriate tissue remodelling by triggering a cascade of reactions (mechanotransduction), being the signal for the adaptation of cells and tissues. However, although the main biological effects of mechanical forces are well documented, the relation between mechanical forces and physiological phenomena is largely unknown. In this paper, some effects of mechanical stresses on different cells (mesenchymal stem cells, bone cells, chondrocyte, endothelial cells, vascular or muscular cells, etc.) are summarized.
人体内几乎所有的细胞都受到机械应力的作用。这些力可以从几帕斯卡(剪切应力)到几兆帕斯卡(髋关节软骨)不等。现在大家都知道机械力对细胞生理有决定性的作用。1880年,W. Roux提出了功能适应的概念;它可以被定义为一种定量的自动调节,由机械力等刺激控制。这些压力影响功能和细胞代谢,并可通过触发级联反应(机械转导)导致适当的组织重塑,这是细胞和组织适应的信号。然而,尽管机械力的主要生物效应有很好的文献记载,但机械力与生理现象之间的关系在很大程度上是未知的。本文综述了机械应力对不同细胞(间充质干细胞、骨细胞、软骨细胞、内皮细胞、血管或肌肉细胞等)的影响。
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引用次数: 1
Age-Related Macular Degeneration Treated with Autologous TelomerasePositive Totipotent Stem Cells 自体端粒阳性全能干细胞治疗老年性黄斑变性
Pub Date : 2020-12-28 DOI: 10.33425/2639-9512.1055
H. Young, M. Speight
Age-related macular degeneration (AMD) is an insidious disease characterized by gradual worsening of symptoms, which in time results in a loss of visual acuity in the central area of vision. Macular degeneration does not result in complete blindness, because peripheral vision remains. However, loss of central vision can make it difficult to perform daily activities, such as reading, driving, recognizing faces, etc. There are two forms of macular degeneration, wet and dry. Wet macular degeneration occurs in about 20% of the cases and can be treated pharmacologically. Dry macular degeneration occurs in about 80% of all cases. It has no known treatment or cure. Currently, the Holy Grail for regenerative medicine for diseases and/or disorders with no known cure involves the use of stem cells. Three types of stem cells have been proposed to treat individuals with macular degeneration, e.g., mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells. We propose a fourth possibility; endogenous adult-derived telomerase-positive totipotent stem cells (TSCs). Autologous TSCs were used to treat four individuals with macular degeneration that had lost their central visual acuity. Two subjects had their central visual acuity restored. The third had serious heart comorbidity and the TSCs treated their body instead, and the fourth individual was non-compliant. The results demonstrated both safety and efficacy (50%) for treating macular degeneration with TSCs.
年龄相关性黄斑变性(AMD)是一种隐蔽性疾病,其特征是症状逐渐恶化,最终导致视觉中心区域的视力丧失。黄斑变性不会导致完全失明,因为周围视力仍然存在。然而,中央视力的丧失会使患者难以进行日常活动,如阅读、驾驶、识别面孔等。黄斑变性有两种形式,湿性和干性。湿性黄斑变性约占20%,可通过药物治疗。干性黄斑变性约占所有病例的80%。目前还没有已知的治疗方法。目前,对于无法治愈的疾病和/或失调,再生医学的圣杯涉及到干细胞的使用。已有三种类型的干细胞被提出用于治疗黄斑变性患者,即间充质干细胞、胚胎干细胞和诱导多能干细胞。我们提出第四种可能性;内源性成人来源的端粒酶阳性的全能干细胞(TSCs)。自体TSCs用于治疗4例失去中央视力的黄斑变性患者。两名受试者的中央视力得到恢复。第三名患者有严重的心脏合并症,TSCs转而治疗他们的身体,第四名患者没有依从。结果显示TSCs治疗黄斑变性的安全性和有效性(50%)。
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引用次数: 7
Autologous Mesenchymal Stem Cells for the Treatment of Amyotrophic Lateral Sclerosis 自体间充质干细胞治疗肌萎缩性侧索硬化
Pub Date : 2020-12-28 DOI: 10.33425/2639-9512.1053
J. Trainini, Gabriel Volman, N. Lago, J. Bordone, Oscar Ectchegoyen, F. Villasante, Facundo Heredia, Yanina Huamanchuco, J. Docampo, Bastarrica María Elena
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引用次数: 0
Holistic Regenerative Medicine and Cell Therapy in Treatment of Diabetes Mellitus: State of The Art Medicine and A Game Changer 整体再生医学和细胞疗法治疗糖尿病:医学的最新进展和游戏规则的改变者
Pub Date : 2020-12-28 DOI: 10.33425/2639-9512.1052
D. Klokol, Lingeswran Nallenthiran, Mike K. S. Chan, M. Wong, V. Chernykh, S. Yefimov, Y. Nalapko, M. Emelianova
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引用次数: 0
Extracorporeal Shock Wave Therapy (Eswt) For the Treatment of Chronic, Non-Healing Wounds: A Case Series 体外冲击波疗法(Eswt)治疗慢性,不愈合伤口:一个案例系列
Pub Date : 2020-12-28 DOI: 10.33425/2639-9512.1057
Belinda Marcus
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引用次数: 0
期刊
Cell, stem cells and regenerative medicine
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