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Stem Cell Treatment of Autism Spectrum Disorders 自闭症谱系障碍的干细胞治疗
Pub Date : 2022-12-31 DOI: 10.33425/2639-9512.1074
Grace Gaston, V. Gallicchio
Autism is a spectrum of neurodevelopmental disorders. It appears differently in all individuals with ASDs and has recently become popular in research. There are many suspected genetic causes of autism, but no cure has been proven to work to treat the disorder. Stem cells have been studied for their potential role in treating ASDs. The most promising results have come from studies utilizing MSCs or hESCs. Experiments have shown that using these stem cells can reduce the severity of autism and increase the quality of life. Stem cells have also been used to model different forms of autism, including Rett Syndrome and Fragile X Syndrome. The most common stem cells used for modeling autism are iPSCs, which can retain the original genetics of the patient it was derived from. By studying autism precisely how it appears in the body, novel drug therapies and treatments can be designed. There are moral considerations that need to be taken into account when studying novel therapies for autism. The most common participants in these studies are children. This population needs to be protected, and researchers should keep their best interests in mind. Also, scientists should acknowledge their work's impact on the general population and hold each other accountable for the work they release.
自闭症是一种神经发育障碍。它在所有自闭症患者身上表现不同,最近在研究中很受欢迎。自闭症有许多被怀疑的遗传原因,但目前还没有被证明可以治愈这种疾病。干细胞在治疗自闭症方面的潜在作用已被研究。最有希望的结果来自利用间充质干细胞或hESCs的研究。实验表明,使用这些干细胞可以减轻自闭症的严重程度,提高生活质量。干细胞也被用于模拟不同形式的自闭症,包括Rett综合征和脆性X染色体综合征。用于自闭症建模的最常见的干细胞是多能干细胞,它可以保留来自患者的原始基因。通过精确地研究自闭症在体内的表现,可以设计出新的药物疗法和治疗方法。在研究自闭症的新疗法时,需要考虑道德因素。这些研究中最常见的参与者是儿童。这个群体需要得到保护,研究人员应该牢记他们的最大利益。此外,科学家应该承认他们的工作对普通大众的影响,并对他们发表的工作负责。
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引用次数: 1
Use of Blood Mononuclear Cells Autologous Fraction for Treatment of Menstrual Disorders (Case Report) 自体血单个核细胞治疗月经紊乱(附1例报告)
Pub Date : 2022-12-31 DOI: 10.33425/2639-9512.1072
Dababsekh I.M, Dababsekh O.V, Lesniak Y.I., Oleksenko N.P.
The aim of our work was to investigate the effectiveness of circulating SC in the blood mononuclear fraction to restore normal functioning of the human ovaries. AH270 patient complained to the clinic about an irregular menstrual cycle in the last 6 months (duration of the menstrual cycle from 38 to 60 days). On day 10 of the menstrual cycle, under general anesthesia, 2 ml of a solution containing a fraction of native nucleus-containing cells isolated from a pool of peripheral blood was administered transvaginally to the right and left ovaries. Microscopic examination of these cells showed that the obtained fraction contains polymorphic nucleus-containing cells of different sizes and high viability, which was 95-98%. After 2 months, the patient came for a follow-up examination, during which an ultrasound of the pelvic organs was performed, as well as laboratory diagnostics of blood tests for AMH and FSH levels. Were taken according to the results of ultrasound of the pelvic organs, the following changes were observed - in the right and left ovaries there were 2 antral follicles in each, up to 3 mm in diameter. The duration of the menstrual cycle after the introduction of stem cells has decreased to 30-35 days. Thus, it is shown that the pool of nuclear-containing peripheral blood cells, which contains circulating progenitors and stem cells, has a powerful regenerative effect with concentrated topical administration, which in this case led to a full functional recovery of the ovaries and normalization of the menstrual cycle.
我们工作的目的是研究循环SC在血液中单个核部分恢复人类卵巢正常功能的有效性。AH270患者向诊所主诉近6个月月经周期不规律(月经周期38 ~ 60天)。在月经周期的第10天,全身麻醉下,从外周血池中分离出含有天然含核细胞部分的溶液2ml经阴道给予左右卵巢。镜检结果表明,所获得的部分含有不同大小的多态含核细胞,存活率为95-98%。2个月后,患者进行了随访检查,期间进行了盆腔器官超声检查,并进行了血液AMH和FSH水平的实验室诊断。根据盆腔器官超声检查结果,观察到以下变化-左右卵巢各有2个窦腔卵泡,直径达3mm。引入干细胞后的月经周期缩短至30-35天。因此,研究表明,含有循环祖细胞和干细胞的含核外周血池具有强大的再生作用,集中局部给药,在这种情况下,导致卵巢功能完全恢复和月经周期正常化。
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引用次数: 0
Novel Bioregenerative Options for Chondrocyte Restoration in Osteoarthritis. 骨关节炎软骨细胞修复的新生物再生选择。
Pub Date : 2022-06-30 DOI: 10.33425/2639-9512.1070
Y. Nalapko, D. Klokol, J. Lakey, O. Adalsteinsson, S. Y. Pan, T. Skutella, M. Wong, Mike K. S. Chan
Cartilage diseases refer to an umbrella of joint disorders, joint injuries and cartilage tumors that are largely characterized by degenerative chondrocyte changes in joints.Osteoarthritis(OA) is the most common form of chronic cartilage diseases, affecting 250 million people and is the fourth leading cause of disability worldwide. The widely used pharmacological treatments for OA have shown limited benefits, and further studies are required. Stem cells have been proposed as regenerative cell therapy for OA to repair and replace the injured cells and tissues with new ones, due to their potential for self-renewal and differentiation into cartilage-forming chondrocytes and immune-modulating capabilities. A number of preclinical and clinical studies have confirmed the potential for mesenchymal stem cells as a novel therapeutic strategy for the treatment of OA. In this review, we look at the promising evidence for stem cell use in OA treatment.
软骨疾病是指关节疾病、关节损伤和软骨肿瘤,主要以关节软骨细胞退行性改变为特征。骨关节炎(OA)是最常见的慢性软骨疾病,影响2.5亿人,是全球第四大致残原因。广泛使用的OA药物治疗显示出有限的益处,需要进一步的研究。由于干细胞具有自我更新和分化成软骨形成软骨细胞和免疫调节能力的潜力,因此已被提出作为OA的再生细胞治疗方法,以修复和替换受损的细胞和组织。许多临床前和临床研究证实了间充质干细胞作为OA治疗新策略的潜力。在这篇综述中,我们着眼于干细胞用于OA治疗的有希望的证据。
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引用次数: 1
Mesenchymal Stem Cell-Mediated Restoration of Ventricle Function 间充质干细胞介导的心室功能恢复
Pub Date : 2022-06-30 DOI: 10.33425/2639-9512.1069
M. Anjum, S. Rajasekar, Kshatriya Prashant, Patel Divyang, Mishra Rangnath, S. S
Mesenchymal Stem cells (MSCs) based interventions in heart failure cases have gained significant interest among researchers and clinicians over the last decade. The ease of their isolation, expansion, high proliferation rate and storage has made MSCs an attractive candidate. MSCs transplanted in patients with ischemic heart disease have been demonstrated to play a significant role in cardiac regeneration through plethora of processes including angiogenesis, myogenesis, immune modulation, anti-apoptotic- and anti-fibrotic-activities. In present study, we have discussed a case of a male patient with severe ventricular dysfunction after an incidence of myocardial infarction. The primary clinical findings demonstrated that the patient had dilated left ventricle (LV) with global LV hypokinesia. The LV ejection fraction (LVEF) was 25%-30%, which is significantly lower than a healthy individual. The patient was treated with adipose derived MSCs, injected through intravenous route. A significant recovery was observed post 5 months with LVEF of 35%. After nine months of follow-up, LVEF improved to 50 % with fair LV systolic function. The LV size was normal, and no regional wall motion abnormality was observed. The study suggests that MSCs infusion can help in restoration of ventricular function.
在过去的十年中,基于间充质干细胞(MSCs)的心力衰竭病例干预已经引起了研究人员和临床医生的极大兴趣。其易于分离、扩增、高增殖率和储存使间充质干细胞成为有吸引力的候选者。缺血性心脏病患者移植的间充质干细胞已被证明在心脏再生过程中发挥重要作用,包括血管生成、肌肉生成、免疫调节、抗凋亡和抗纤维化活性。在本研究中,我们讨论了一例男性患者在心肌梗死发生后出现严重的心室功能障碍。初步临床表现表明,患者有左心室扩张(LV)和整体左室运动不足。左室射血分数(LVEF)为25% ~ 30%,明显低于健康人。患者接受脂肪来源的间充质干细胞治疗,通过静脉注射。5个月后观察到明显的恢复,LVEF为35%。随访9个月后,LVEF改善至50%,左室收缩功能正常。左室大小正常,未见局部壁运动异常。本研究提示灌注间充质干细胞有助于心室功能的恢复。
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引用次数: 0
Stem Cell and Regenerative Methods for Space Personnel 太空人员的干细胞和再生方法
Pub Date : 2021-12-30 DOI: 10.33425/2639-9512.1066
E. R. Vickers, Haitao Wen
Significant deterioration of organs and tissues occurs in astronauts as a result of cosmic radiation exposure. This is a major obstacle to the developing space industry involving extended space exploration, commercial asteroid mining and the colonization of Earth’s moon and Mars. Cosmic radiation includes galactic cosmic rays, and solar particle events of x-rays and gamma rays that penetrate deeply inducing DNA damage. Potential medical issues for astronauts arising from radiation include cancer, rapid aging, sterility, impaired immune system, re-emergence of pathogenic viruses, neurodegeneration and memory impairment. In summary, there are potentially catastrophic consequences for space personnel from prolonged exposure to radiation. Upregulating the regeneration of tissue using advances in stem cell technology would be a plausible method to counteract radiation damage triggering cellular degeneration. Stem cells are ‘survival’ cells and are responsible for the ongoing repair and regeneration of the human body. Increasing the number of available stem cells improves the regenerative capacity of the body. Current stem cell technology is not possible in space, as it requires multiple medical specialists using major hospital surgical and laboratory equipment. The authors have developed a portable stem cell biotechnology kit that is compact, lightweight, and simple to operate and could be performed by astronauts in space on a frequent basis to potentially regenerate affected tissue and reverse the effects of cosmic radiation. The technology uses laboratory validated peptide hydrogels for stem cell migration and expansion. The astronaut only requires donating a small amount of blood or adipose tissue. Preliminary analysis showed stem cells have high yield, excellent cell viability, and demonstrate normal stem cell health parameters of autophagy and annexin V. This approach may help to balance the degeneration / regeneration cycle of the body subject to radiation. Space personnel can be trained in a short period of time to perform the technology with safety and efficacy.
由于宇宙辐射暴露,宇航员的器官和组织会出现严重的退化。这是发展空间工业的主要障碍,包括扩展空间探索、商业小行星采矿以及地球月球和火星的殖民化。宇宙辐射包括银河宇宙射线,以及太阳粒子事件的x射线和伽马射线,它们会穿透并导致DNA损伤。辐射给宇航员带来的潜在医疗问题包括癌症、快速衰老、不育、免疫系统受损、致病性病毒重新出现、神经退化和记忆障碍。总而言之,长期暴露在辐射下可能对空间工作人员造成灾难性后果。利用先进的干细胞技术来调节组织再生可能是一种对抗辐射损伤引发的细胞退化的可行方法。干细胞是“存活”细胞,负责人体的持续修复和再生。增加可用干细胞的数量可以提高身体的再生能力。目前的干细胞技术在太空是不可能实现的,因为它需要多名医学专家使用大型医院的外科和实验室设备。作者已经开发出一种便携式干细胞生物技术试剂盒,它紧凑、轻便、操作简单,可以由宇航员在太空中经常进行,以潜在地再生受影响的组织,并逆转宇宙辐射的影响。该技术使用实验室验证的肽水凝胶进行干细胞迁移和扩增。宇航员只需要捐献少量的血液或脂肪组织。初步分析表明,干细胞产量高,细胞活力良好,并表现出正常的自噬和膜联蛋白v的干细胞健康参数,这种方法可能有助于平衡辐射作用下身体的退化/再生周期。空间人员可以在短时间内接受培训,安全有效地执行这项技术。
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引用次数: 0
The Transplantation of Human Pluripotent Stem Cells is Safe: A Personal Experience during the Past 5 Years (I) 人类多能干细胞移植是安全的:过去5年的个人经验(一)
Pub Date : 2021-12-30 DOI: 10.33425/2639-9512.1068
Taihua Wang, Xiaohui Cui, Zhenzhen Yang, Linyu Cui, Rongrong Li, Xinyi Shi, X. Jiang, Shufeng Du, Mengqian Wang, Guoke Yang, Ying Meng, Gang Zhang
The greatest dilemma of human pluripotent stem cell transplantation therapy clinically is the potential risk to form teratomas in the recipient’s body. On the one hand, to date, no data can confirm this risk. On the other hand, no data can confirm the safety of human pluripotent stem cell transplantations, either. To break this dilemma, the correspondence author, G Z, decided to accept human pluripotent stem cell transplantations voluntarily. During the past five years, G Z accepted totally 77 times human stem cell transplantations with/without overexpressing different human genes, and the whole number of human stem cells was up to approximately 6.36 X 109 . After medical examinations, the results demonstrated that G Z’s health conditions were basically normal. Thus, our investigations preliminarily proved that intravenous transplantations of human pluripotent stem cells were safe so far, at least for this case.
临床应用人类多能干细胞移植治疗的最大难题是在受者体内形成畸胎瘤的潜在风险。一方面,到目前为止,没有数据可以证实这种风险。另一方面,也没有数据可以证实人类多能干细胞移植的安全性。为了打破这种困境,通信作者gz决定自愿接受人类多能干细胞移植。在过去的五年中,gz共接受了77次有/没有过表达不同人类基因的人类干细胞移植,人类干细胞总数约为6.36 X 109。经医学检查,gz的健康状况基本正常。因此,我们的研究初步证明,到目前为止,静脉内移植人类多能干细胞是安全的,至少对这个病例来说是安全的。
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引用次数: 0
Endogenous Self Organ Repairing after Release of Unilateral Ureteral Obstruction (RUUO) 单侧输尿管梗阻解除后的内源性自体器官修复
Pub Date : 2021-12-30 DOI: 10.33425/2639-9512.1067
S. Kulkarni
Citation: Shrikant L. Kulkarni. Endogenous Self Organ Repairing after Release of Unilateral Ureteral Obstruction (RUUO). Stem Cells Regen Med. 2021; 4(4): 1-3. Kulkarni Clinic, 175/1 Balwant Station Road, Near Post Office, Chinch wad Gaon Pune 411033, Maharashtra, India. *Correspondence: Dr. Shrikant L. Kulkarni, Kulkarni Clinic, 175/1 Balwant Station Road, Near Post Office, Chinch wad Gaon Pune 411033, Maharashtra, India.
引用本文:Shrikant L. Kulkarni。单侧输尿管梗阻解除后的内源性自体器官修复。干细胞再生医学,2021;4(4): 1 - 3。Kulkarni诊所,印度马哈拉施特拉邦Pune, Chinch wad Gaon, Balwant车站路175/1,近邮局411033。*通信:Shrikant L. Kulkarni医生,Kulkarni诊所,印度马哈拉施特拉邦,钦奇瓦德加恩浦那411033,巴尔旺特车站路175/1号,近邮局。
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引用次数: 0
The Cure of Human Type 2 Diabetes via Systematic Transplantations of dgHPSCs Overexpressing Human ERRy and/or Insulin Genes (I) 通过系统移植表达人ERRy和/或胰岛素基因的dgHPSCs治疗2型糖尿病(I)
Pub Date : 2021-12-30 DOI: 10.33425/2639-9512.1065
Taihua Wang, Xiaohui Cui, Zhenzhen Yang, Linyu Cui, Rongrong Li, Xinyi Shi, Xiaoxia Jiang, Shufeng Du, Mengqian Wang, N. Zuo, Guoke Yang, Ying Meng, Gang Zhang
Although insulin (INS) injection is widely administrated clinically for the treatment of human type 2 diabetes (T2D), this method cannot effectively prohibit the progressing of diabetes complications. Previously, we demonstrated that daily INS injections could be replaced by transplantations of directly-generated human pluripotent stem cells (dgHPSCs) overexpressing human INS and/or estrogen-related receptor γ (ERRγ) genes. In this investigation, we further revealed that systematic transplantations of dgHPSCs overexpressing INS and/or ERRγ genes could completely replaced the INS injections of T2D patient, and the patient’s blood glucose and HbA1c levels were kept around the normal ranges. Hence, this study provided an important strategy for the eventually cure of human T2D disease through human stem cell and gene therapy.
虽然胰岛素(INS)注射在临床上广泛用于治疗2型糖尿病(T2D),但这种方法并不能有效地阻止糖尿病并发症的发展。在此之前,我们证明了每日INS注射可以被直接生成的人多能干细胞(dgHPSCs)移植所取代,dgHPSCs过度表达人INS和/或雌激素相关受体γ (ERRγ)基因。在本研究中,我们进一步发现系统移植过表达INS和/或ERRγ基因的dgHPSCs可以完全替代T2D患者的INS注射,患者的血糖和HbA1c水平保持在正常范围内。因此,本研究为通过人类干细胞和基因治疗最终治愈人类T2D疾病提供了重要的策略。
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引用次数: 1
An Alternative Novel Therapy for the Treatment of Chronic Inflammatory Demyelinating Polyneuropathy: Adult Autologous Telomerase-Positive Stem Cells 一种治疗慢性炎症性脱髓鞘性多神经病变的新疗法:成人自体端粒酶阳性干细胞
Pub Date : 2021-12-30 DOI: 10.33425/2639-9512.1064
H. Young, M. Speight
Chronic inflammatory demyelinating polyneuropathy, e.g., chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), is a rare autoimmune mediated peripheral neuropathy. CIDP is defined as symptomology of greater than two months duration and electro diagnostic evidence of peripheral nerve demyelination. The estimated overall prevalence of CIDP is 4.8 to 8.9 cases per 100,000 people. Symptomology includes motor, sensory, and autonomic involvement resulting in symmetrical proximal and distal muscle weakness, loss of strength, areflexia of greater than eight weeks duration, numbness, weakness, sensory ataxia, paresthesia, decreased peripheral temperature, and gait disorder. As CIDP progresses there is axonal loss within mixed peripheral nerves secondary to demyelination, which is associated with a poor prognosis. Autoantibodies identified for CIDP thus far include contactin-1 (CNTN1), contactin-associated protein-1 (Caspr1), contactin-2 (CNTN2), neurofascin-155 (Nfasc-155), neurofascin-140/186(Nfasc-140/186), LM1, gliomedin, and vinculin. Another marker of CIDP is sphingomyelin protein in the cerebral spinal fluid. Potential treatment options for CIDP are first-line therapies, such as corticosteroids, plasma exchange, and/or immunoglobulins. If patients are refractory to first-line treatments to halt progression of the disease, then second-line therapies, such as chemotherapeutic drugs, immunosuppressive drugs, and/or immunomodulatory drugs, are utilized. Lastly, if first- and second-line therapies fail, novel unconventional therapies have been utilized, such as high-dose cyclophosphamide to eradicate a defective immune system containing CIDP-associated autoantibodies to nodal and par anodal proteins. This is then followed with either autologous or HLA-matched allogeneic hematopoietic stem cell transplantation (HSCT) with the intent to replace the defective immune system with a normal immune system absent of CIDP-associated autoantibodies. Whatever therapeutic treatment regimen(s) is/are utilized, maintenance treatments are required for years to maintain stasis in individuals with CIDP. Unfortunately, while first-line, second-line, and/or HSCT treatments may halt the progression of the CIDP and maintain individuals in stasis, they do little to restore neurophysiological function to the individual. We proposed an alternative unconventional therapy to treat CIDP, the use of adult autologous adult telomerase positive stem cells to halt progression of the disease and restore (neuro-) physiological function to the tissues. This hypothesis was based on previous clinical studies utilizing telomerase positive stem cells with Parkinson disease, Alzheimer’s disease, age- related dry macular degeneration, traumatic blindness, traumatic spinal cord injury, myocardial infarction, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, celiac disease, systemic lupus erythematosus, and osteoarthritis. Within this small cohort (n=3) clinical stu
慢性炎症性脱髓鞘多神经病变,如慢性炎症性脱髓鞘多根神经病变(CIDP),是一种罕见的自身免疫介导的周围神经病变。CIDP定义为症状持续时间超过两个月,并有周围神经脱髓鞘的电诊断证据。估计CIDP的总体患病率为每10万人4.8至8.9例。症状包括运动、感觉和自主神经受累,导致对称的近端和远端肌肉无力、力量丧失、持续时间超过8周的反射反射、麻木、无力、感觉共济失调、感觉异常、外周温度下降和步态障碍。随着CIDP的进展,继发于脱髓鞘的混合周围神经出现轴突损失,这与预后不良有关。目前已鉴定的CIDP自身抗体包括接触蛋白-1 (CNTN1)、接触蛋白相关蛋白-1 (Caspr1)、接触蛋白-2 (CNTN2)、神经束蛋白-155 (Nfasc-155)、神经束蛋白-140/186(Nfasc-140/186)、LM1、胶质瘤蛋白和血管蛋白。CIDP的另一个标志是脑脊液中的鞘磷脂蛋白。CIDP的潜在治疗选择是一线治疗,如皮质类固醇、血浆置换和/或免疫球蛋白。如果患者对阻止疾病进展的一线治疗难以耐受,则使用二线治疗,如化疗药物、免疫抑制药物和/或免疫调节药物。最后,如果一线和二线治疗失败,新的非常规疗法已被使用,如大剂量环磷酰胺,以根除有缺陷的免疫系统含有与cidp相关的自身抗体节点和par节点蛋白。然后进行自体或hla匹配的异体造血干细胞移植(HSCT),目的是用不存在与cidp相关的自身抗体的正常免疫系统取代有缺陷的免疫系统。无论采用何种治疗方案,都需要多年的维持治疗来维持CIDP患者的停滞状态。不幸的是,虽然一线、二线和/或HSCT治疗可能会阻止CIDP的进展并使个体处于停滞状态,但它们对恢复个体的神经生理功能几乎没有作用。我们提出了一种替代的非常规疗法来治疗CIDP,使用成人自体成人端粒酶阳性干细胞来阻止疾病的进展并恢复组织的(神经)生理功能。这一假设是基于先前的临床研究,利用端粒酶阳性干细胞治疗帕金森病、阿尔茨海默病、年龄相关性干性黄斑变性、创伤性失明、创伤性脊髓损伤、心肌梗死、慢性阻塞性肺病、特发性肺纤维化、乳糜泻、系统性红斑狼疮和骨关节炎。在这个小队列(n=3)临床研究中,没有报告任何接受治疗的参与者出现不良事件。虽然没有直接证据表明自体端粒酶阳性干细胞对其中两名参与者的结果有贡献,但有间接证据表明神经生理功能的恢复。这在运动、感觉和自主神经功能的恢复方面得到了证明,例如,力量增加,感觉输入恢复,反射恢复,麻木消失,血流量增加,四肢体温正常,步态正常。间接地,这表明自体端粒酶阳性干细胞是安全的,并且在阻止慢性炎症性脱髓鞘性多神经病变的进展和恢复神经生理功能方面显示出66%的功效。
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引用次数: 0
Differentiation of Mouse Embryonic Fibroblasts (MEFs) into Cardiomyocytes Using Human-Derived Cardiac Inducing RNA (CIR) 利用人源性心脏诱导RNA (CIR)诱导小鼠胚胎成纤维细胞向心肌细胞分化
Pub Date : 2021-06-30 DOI: 10.33425/2639-9512.1062
L. Lemanski, A. Kochegarov, K. Kaveh, Michael Neal, A. Arms, Yelica L Rodriguez, Lan Hong, M. J. Equbal, Pipasha Biswas, Priya Biswas, M. Gonzalez, Jewel Ross-Ferguson, Justin Rusk, Lani Lyman- Henley, Tearah McRae-Kee, Curtis Ivory, Zhengshan Zhao
The present study explores an RNA we have discovered in human heart that induces differentiation of mouse embryonic stem cells and human induced pluripotent stem cells into cardiomyocytes in vitro. We have designated this RNA as Cardiac Inducing RNA or CIR. We now find that CIR also induces mouse embryonic fibroblasts (MEF) to form cardiomyocytes in vitro. For these studies, human-derived CIR is transfected into MEF using lipofectamine. The CIR-transfected mouse fibroblasts exhibit spindle-shaped cells, characteristic of myocardial cells in culture and express cardiac-specific troponin-T and cardiac tropomyosin. As such, the CIR-induced conversion of the fibroblasts into cardiomyocytes in vitro appears to take place without initial dedifferentiation into pluripotent stem cells. Instead, after CIR transfection using a lipofectamine transfection system, over the next 8 days there appears to be a direct transdifferentiation of ˃80% of the cultured fibroblasts into definitive cardiomyocytes. Fewer than ˂7% of the untreated controls using non-active RNA or lipofectamine by itself show cardiomyocyte characteristics. Thus, discovery of CIR may hold significant potential for future use in repair/regeneration of damaged myocardial tissue in humans after myocardial infarction or other disease processes such that affected patients may be able to return to pre-heart-disease activity levels.
本研究探索了我们在人类心脏中发现的一种RNA,该RNA在体外诱导小鼠胚胎干细胞和人诱导多能干细胞分化为心肌细胞。我们将这种RNA命名为心脏诱导RNA或CIR,我们现在发现CIR也能诱导小鼠胚胎成纤维细胞(MEF)在体外形成心肌细胞。在这些研究中,使用脂质体将人源性CIR转染到MEF中。转染了cirr的小鼠成纤维细胞呈现梭形细胞,这是培养心肌细胞的特征,并表达心肌特异性肌钙蛋白-t和心肌原肌球蛋白。因此,在体外,cirr诱导的成纤维细胞向心肌细胞的转化似乎没有初始去分化为多能干细胞。相反,在使用脂质体转染系统转染CIR后,在接下来的8天内,培养的成纤维细胞˃80%似乎直接转分化为最终的心肌细胞。在使用非活性RNA或脂质胺的对照组中,只有不到Ë 7%的人表现出心肌细胞特征。因此,CIR的发现可能具有重大的潜力,用于心肌梗死或其他疾病过程后人类受损心肌组织的修复/再生,使受影响的患者能够恢复到心脏病前的活动水平。
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引用次数: 1
期刊
Cell, stem cells and regenerative medicine
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