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Complete lasting reversal of polycystic ovary syndrome from intravenous umbilical cord derived mesenchymal stem cell infusion. 静脉输注脐带间充质干细胞可完全持久逆转多囊卵巢综合征。
IF 1.5 Q4 CELL BIOLOGY Pub Date : 2024-08-25 eCollection Date: 2024-01-01 DOI: 10.62347/TCZF4814
Chadwick Prodromos, Keanne Jabbarzadeh, Mark Hirmiz

Polycystic ovary syndrome (PCOS) presents distressing symptoms and stands as a primary cause of infertility. Currently, treatment options are limited to symptom management. This article presents a case study of a patient suffering from hair thinning associated with PCOS, treated with intravenous and subdermal injections of umbilical cord-derived mesenchymal stem cells (UC-MSCs). Remarkably, following treatment, the patient's 14-year history of menstrual irregularities and hormonal imbalances completely resolved, alongside the disappearance of ovarian cysts, with these improvements persisting for well over a year. Given PCOS's recognized inflammatory nature and the potent anti-inflammatory properties of UC-MSCs, we propose inflammation modulation as the likely mechanism of action. Further exploration is underway, actively seeking additional PCOS patients to ascertain whether similar therapeutic effects are reproducible or if this case represents an anomaly. This case underscores the potential of stem cell therapy as a revolutionary approach to PCOS management, addressing symptomatic relief and potentially underlying pathogenic mechanisms. The sustained clinical benefits observed advocate for comprehensive investigation into the efficacy and mechanisms of stem cell therapy in PCOS management.

多囊卵巢综合征(PCOS)会出现令人痛苦的症状,是导致不孕不育的主要原因之一。目前,治疗方法仅限于对症治疗。本文介绍了一个病例研究,患者因多囊卵巢综合征而头发稀疏,通过静脉注射和皮下注射脐带间充质干细胞(UC-MSCs)进行治疗。值得注意的是,治疗后,患者14年的月经不调和内分泌失调病史完全消失,卵巢囊肿也随之消失,这些改善持续了一年多。鉴于多囊卵巢综合症具有公认的炎症性质,而 UC 间充质干细胞具有强大的抗炎特性,我们认为炎症调节可能是其作用机制。我们正在进一步探索,积极寻找更多的多囊卵巢综合症患者,以确定类似的治疗效果是否具有可重复性,或者这个病例是否代表了一种异常现象。该病例强调了干细胞疗法作为治疗多囊卵巢综合症的革命性方法的潜力,既能缓解症状,又能解决潜在的致病机制。观察到的持续临床益处主张对干细胞疗法治疗多囊卵巢综合症的疗效和机制进行全面调查。
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引用次数: 0
Examining the level of inflammatory cytokines TNF-α and IL-8 produced by osteoblasts differentiated from dental pulp stem cells. 研究由牙髓干细胞分化而成的成骨细胞产生的炎症细胞因子 TNF-α 和 IL-8 的水平。
IF 1.5 Q4 CELL BIOLOGY Pub Date : 2024-08-25 eCollection Date: 2024-01-01 DOI: 10.62347/CBMW4366
Sahar Khastar, Mandana Sattari

Background: The use of dental pulp stem cells (DPSCs) in clinical applications instead of bone marrow stem cells is a very promising method capable of significantly changing the future of medical treatment. If further studies prove that DPSCs and the cells differentiated from them do not stimulate the immune system, these cells can be used more reliably in treatment of autoimmune diseases.

Methods: In this research, we examined the isolated DPSCs and differentiated osteoblasts from them in medium without inflammatory stimulants in terms of TLR3 and TLR4 gene expression and inflammatory cytokines, including TNF-α and IL-8 using qRT-PCR, and measured the concentration of inflammatory cytokines IL-8 and TNF-α produced by these two types of cells through ELISA.

Results: The obtained results showed that the expression level of inflammatory cytokines IL-8 and TNF-α in differentiated osteoblasts is significantly different as compared with DPSCs. However, no significant difference was observed in TLR-4 expression between two groups. An increase in TNF-α expression level was found to directly correlate with an increase in the expression of IL-8. The concentration of cytokine TNF-α in osteoblasts was significantly higher than that of IL-8 in DPSCs.

Conclusion: In comparison to DPSCs, osteoblast cells first lead to inflammatory responses. These responses reduce overtime. However, DPSCs retain their immunomodulatory properties and do not show inflammatory responses.

背景:在临床应用中使用牙髓干细胞(DPSCs)代替骨髓干细胞是一种非常有前途的方法,能够极大地改变医疗的未来。如果进一步的研究证明牙髓干细胞及其分化出的细胞不会刺激免疫系统,那么这些细胞就能更可靠地用于治疗自身免疫性疾病:本研究采用 qRT-PCR 技术检测了在不含炎症刺激物的培养基中分离出的 DPSCs 及其分化出的成骨细胞的 TLR3 和 TLR4 基因表达以及包括 TNF-α 和 IL-8 在内的炎症细胞因子,并通过 ELISA 方法测定了这两种细胞产生的炎症细胞因子 IL-8 和 TNF-α 的浓度:结果表明,与 DPSCs 相比,炎性细胞因子 IL-8 和 TNF-α 在分化成骨细胞中的表达水平有显著差异。然而,在 TLR-4 的表达上,两组之间没有观察到明显差异。研究发现,TNF-α表达水平的增加与IL-8表达的增加直接相关。成骨细胞中细胞因子 TNF-α 的浓度明显高于 DPSCs 中 IL-8 的浓度:结论:与 DPSCs 相比,成骨细胞首先导致炎症反应。结论:与 DPSCs 相比,成骨细胞首先会导致炎症反应,这些反应会随着时间的推移而减少。结论:与 DPSCs 相比,成骨细胞首先会导致炎症反应,但随着时间的推移,这些反应会逐渐减弱。然而,DPSCs 保留了其免疫调节特性,不会出现炎症反应。
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引用次数: 0
Exploring the application of stem cell technology in treating sensorineural hearing loss. 探索干细胞技术在治疗感音神经性听力损失中的应用。
IF 1.5 Q4 CELL BIOLOGY Pub Date : 2024-08-25 eCollection Date: 2024-01-01 DOI: 10.62347/AEIV5813
Min Li, Rongyue Ma, Qing Li, Min Guo

Sensorineural deafness mainly occurs due to damage to hair cells, and advances in stem cell technology, especially the application of induced pluripotent stem cells (iPSCs) and adult stem cells, provides new possibilities for hair cell regeneration. This review describes the basic knowledge of stem cells and their important applications in regenerative medicine, as well as recent progress in stem cell research in the field of hair cell regeneration, especially the induced differentiation of hair-like cells. At the same time, we also point out the challenges facing current research, including differentiation efficiency, cell stability issues, and treatment safety and long-term efficacy considerations. Finally, we look forward to the direction of future research, and emphasize the importance of the cell differentiation mechanism, simulation of the inner ear microenvironment, safety assessment, and personalized treatment strategies. In conclusion, despite many challenges, stem cell technology has shown great potential in the field of hearing research and is expected to bring revolutionary treatment options for patients with sensorineural hearing loss in the future.

感音神经性耳聋主要是由于毛细胞受损所致,干细胞技术的进步,特别是诱导多能干细胞(iPSC)和成体干细胞的应用,为毛细胞再生提供了新的可能性。本综述介绍了干细胞的基础知识及其在再生医学中的重要应用,以及干细胞研究在毛细胞再生领域的最新进展,特别是毛发样细胞的诱导分化。同时,我们也指出了当前研究面临的挑战,包括分化效率、细胞稳定性问题,以及治疗安全性和长期疗效方面的考虑。最后,我们展望了未来的研究方向,并强调了细胞分化机制、内耳微环境模拟、安全性评估和个性化治疗策略的重要性。总之,尽管面临诸多挑战,干细胞技术在听力研究领域已显示出巨大潜力,有望在未来为感音神经性听力损失患者带来革命性的治疗方案。
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引用次数: 0
Cellular therapies for idiopathic pulmonary fibrosis: current progress and future prospects. 特发性肺纤维化的细胞疗法:当前进展与未来展望。
IF 1.5 Q4 CELL BIOLOGY Pub Date : 2024-08-25 eCollection Date: 2024-01-01 DOI: 10.62347/DAKS5508
Nicholas T Le, Matthew W Dunleavy, Rebecca D Kumar, William Zhou, Sumrithbir S Bhatia, Ahmed H El-Hashash

Idiopathic pulmonary fibrosis (IPF) is an interstitial, fibrotic lung disease characterized by progressive damage. Lung tissues with IPF are replaced by fibrotic tissues with increased collagen deposition, modified extracellular matrix, all which overall damages the alveoli. These changes eventually impede the gas exchange function of the alveoli, and eventually leads to fatal respiratory failure of the lung. Investigations have been conducted to further understand IPF's pathogenesis, and significant progress in understanding its development has been made. Additionally, two therapeutic treatments, Nintedanib and Pirfenidone, have been approved and are currently used in medical applications. Moreover, cell-based treatments have recently come to the forefront of developing disease therapeutics and are the focus of many current studies. Furthermore, a sizable body of research encompassing basic, pre-clinical, and even clinical trials have all been amassed in recent years and hold a great potential for more widespread applications in patient care. Herein, this article reviews the progress in understanding the pathogenesis and pathophysiology of IPF. Additionally, different cell types used in IPF therapy were reviewed, including alveolar epithelial cells (AECs), circulating endothelial progenitors (EPCs), mixed lung epithelial cells, different types of stem cells, and endogenous lung tissue-specific stem cells. Finally, we discussed the contemporary trials that employ or explore cell-based therapy for IPF.

特发性肺纤维化(IPF)是一种以进行性损伤为特征的间质性纤维化肺病。患 IPF 的肺组织会被纤维化组织取代,胶原沉积增加,细胞外基质发生改变,所有这些都会对肺泡造成整体损害。这些变化最终会阻碍肺泡的气体交换功能,最终导致致命的肺部呼吸衰竭。为了进一步了解 IPF 的发病机理,人们进行了大量研究,并在了解其发展方面取得了重大进展。此外,宁替达尼(Nintedanib)和吡非尼酮(Pirfenidone)这两种治疗方法已经获得批准,目前正在医疗应用中。此外,以细胞为基础的治疗方法最近已成为开发疾病疗法的前沿,也是当前许多研究的重点。此外,近年来还积累了大量的研究成果,包括基础研究、临床前研究、甚至临床试验,这些研究成果为在患者护理中更广泛的应用提供了巨大的潜力。本文回顾了人们在了解 IPF 发病机制和病理生理学方面取得的进展。此外,还回顾了用于治疗 IPF 的不同细胞类型,包括肺泡上皮细胞(AECs)、循环内皮祖细胞(EPCs)、混合肺上皮细胞、不同类型的干细胞和内源性肺组织特异性干细胞。最后,我们讨论了采用或探索细胞疗法治疗 IPF 的当代试验。
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引用次数: 0
Fetal progenitor cells for treatment of chronic limb ischemia. 胎儿祖细胞用于治疗慢性肢体缺血。
IF 1.5 Q4 CELL BIOLOGY Pub Date : 2024-06-15 eCollection Date: 2024-01-01 DOI: 10.62347/MZKI8393
Oleksandr Kukharchuk, Abhijit Bopardikar, Padma Priya Anand Baskaran, Andrii Kukharchuk, Rohit Kulkarni, Ranjit Ranbhor

Objectives: This study investigated the therapeutic potential of fetal progenitor cells (FPCs) in the treatment of chronic non-healing wounds and ulcers associated with chronic limb ischemia (CLI). The research aimed to elucidate the mechanism of action of FPCs and evaluate their efficacy and safety in CLI patients.

Methods: The researchers isolated FPCs from aborted human fetal liver, brain, and skin tissues and thoroughly characterized them. The preclinical phase of the study involved assessing the effects of FPCs in a rat model of CLI. Subsequently, a randomized controlled clinical trial was conducted to compare the efficacy of FPCs with standard treatment and autologous bone marrow mononuclear cells in CLI patients. The clinical trial lasted 12 months, with a follow-up period of 24-36 months. The primary outcomes included wound healing, frequency of major and minor amputations, pain reduction, and the incidence of complications. Secondary outcomes involved changes in local hemodynamics and histological, ultrastructural, and immunohistochemical assessments of angiogenesis.

Results: In the animal model, FPC treatment significantly enhanced angiogenesis and accelerated healing of ischemic wounds compared to controls. The clinical trial in CLI patients demonstrated that the FPC therapy achieved substantially higher rates of complete wound closure, prevention of major amputation, pain reduction, and improvement in ankle-brachial index compared to control groups. Notably, the study reported no serious adverse events.

Conclusions: FPC therapy exhibited remarkable efficacy in promoting the healing of ischemic wounds, preventing amputation, and improving symptoms and quality of life in patients with CLI. The proangiogenic and provasculogenic effects of FPCs may be attributed to their ability to secrete specific growth factors. These findings provide new insights into the development of cellular therapeutic angiogenesis as a promising approach for the treatment of peripheral arterial diseases.

研究目的本研究探讨了胎儿祖细胞(FPCs)在治疗与慢性肢体缺血(CLI)相关的慢性不愈合伤口和溃疡方面的治疗潜力。研究旨在阐明胎儿祖细胞的作用机制,并评估其对慢性肢体缺血患者的疗效和安全性:研究人员从流产的人类胎儿肝脏、大脑和皮肤组织中分离出 FPCs,并对其进行了全面鉴定。临床前阶段的研究包括评估 FPCs 在急性脑梗塞大鼠模型中的效果。随后,进行了一项随机对照临床试验,以比较 FPCs 与标准疗法和自体骨髓单核细胞对 CLI 患者的疗效。临床试验为期 12 个月,随访期为 24-36 个月。主要结果包括伤口愈合、大截肢和小截肢的频率、疼痛减轻以及并发症的发生率。次要结果包括局部血流动力学变化以及血管生成的组织学、超微结构和免疫组化评估:结果:在动物模型中,与对照组相比,FPC 治疗明显促进了血管生成,加快了缺血性伤口的愈合。对慢性缺血性心肌梗死患者进行的临床试验表明,与对照组相比,FPC疗法在伤口完全愈合率、防止大截肢率、减轻疼痛率和改善踝肱指数方面均有大幅提高。值得注意的是,该研究未报告严重不良事件:结论:FPC疗法在促进缺血性伤口愈合、预防截肢、改善CLI患者症状和生活质量方面疗效显著。FPCs 的促血管生成和促血管生成作用可能归因于其分泌特定生长因子的能力。这些发现为细胞治疗性血管生成的发展提供了新的视角,是治疗外周动脉疾病的一种前景广阔的方法。
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引用次数: 0
Human corneal endothelial cell transplantation with nanocomposite gel sheet preserves corneal stability in post-corneal transplant bullous keratopathy: a 16-year follow-up. 用纳米复合凝胶片移植人角膜内皮细胞可保持角膜移植后大疱性角膜病的角膜稳定性:16 年随访。
IF 1.5 Q4 CELL BIOLOGY Pub Date : 2024-06-15 eCollection Date: 2024-01-01 DOI: 10.62347/CBYH7014
Periasamy Parikumar, Kazutoshi Haraguchi, Rajappa Senthilkumar, Samuel Jk Abraham

Post-corneal transplantation endothelial decompensation and subsequent bullous keratopathy often result in unfavorable clinical outcomes regardless of the treatment strategy employed. In this report, we present the outcomes of a patient managed with in vitro expanded human corneal endothelial cell (HCEC) transplantation facilitated by a nanocomposite gel (NC gel) sheet over 16 years. A 40-year-old male patient who presented with signs of graft failure after penetrating keratoplasty underwent HCEC transplantation. Additionally, HCECs were obtained from a deceased donor, cultured in vitro, and transplanted onto an NC gel sheet as a temporary scaffold to support the transplanted cells until engraftment. At the 16-year follow-up, the cornea had remained stable and did not exhibit active disease manifestations. Notably, no new bullae were formed, and the epithelial surface appeared smooth without signs of active fluid transport abnormalities. Although a slight reduction in corneal thickness was observed, the disease-free region at the time of the intervention remained transparent. HCEC transplantation with NC gel sheets is a promising, minimally invasive approach for achieving long-term corneal stability in cases of bullous keratopathy following corneal graft failure. Importantly, this technique circumvents the need for complex procedures and utilizes corneal endothelial precursors derived from donor corneas discarded for lack of sufficient endothelial cells. After in vitro culture, these cells were successfully transplanted in three patients, proving that one donated eye can be useful in treating three eyes of three patients. This technique addresses the donor cornea shortage concerns and makes our concept "an-eye-for-eyes", a reality.

角膜移植后内皮失代偿和随后的大疱性角膜病通常会导致不利的临床结果,无论采用何种治疗策略。在本报告中,我们介绍了一名患者在纳米复合凝胶(NC 凝胶)薄片的帮助下,通过体外扩增人角膜内皮细胞(HCEC)移植治疗 16 年后的结果。一名 40 岁的男性患者在穿透性角膜移植术后出现移植失败迹象,于是接受了 HCEC 移植手术。此外,我们还从一名已故捐赠者那里获得了高促性红细胞生成素,经体外培养后移植到 NC 凝胶片上作为临时支架,以支持移植细胞直至其吸收。在 16 年的随访中,角膜一直保持稳定,没有出现活动性疾病表现。值得注意的是,角膜上没有形成新的鼓泡,上皮表面光滑,没有液体运输异常的迹象。虽然观察到角膜厚度略有下降,但干预时的无病区域仍然是透明的。对于角膜移植失败后出现的大疱性角膜病,使用 NC 凝胶片移植 HCEC 是一种很有前景的微创方法,可实现角膜的长期稳定。重要的是,这项技术避免了复杂的手术过程,利用的角膜内皮前体来自因缺乏足够内皮细胞而被丢弃的供体角膜。经过体外培养,这些细胞成功移植到三名患者体内,证明了一只捐献的眼睛可以用于治疗三名患者的三只眼睛。这项技术解决了供体角膜短缺的问题,使我们的 "以眼换眼 "理念成为现实。
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引用次数: 0
Evaluation of osteoconductive effect of polycaprolactone (PCL) scaffold treated with fibronectin on adipose-derived mesenchymal stem cells (AD-MSCs). 评估经纤维连接蛋白处理的聚己内酯(PCL)支架对脂肪间充质干细胞(AD-MSCs)的骨诱导作用。
IF 1.5 Q4 CELL BIOLOGY Pub Date : 2024-06-15 eCollection Date: 2024-01-01 DOI: 10.62347/DMKY5924
Reyhaneh Saadat Rezaee Asl, Fatemeh Rahimzadeh-Bajgiran, Ehsan Saburi

Background: Replacing damaged organs or tissues and repairing damage by tissue engineering are attracting great interest today. A potentially effective method for bone remodeling involves combining nanofiber scaffolds with extracellular matrix (ECM), and growth factors. Today, electrospun PCL-based scaffolds are widely used for tissue engineering applications.

Methods: In this study, we used an electrospun polycaprolactone (PCL) scaffold coated with fibronectin (Fn), a ubiquitous ECM glycoprotein, to investigate the induction potential of this scaffold in osteogenesis with adipose-derived mesenchymal stem cells (AD-MSCs).

Results: Scanning electron microscopy (SEM) analysis showed that fibronectin, by binding to the membrane receptors of mesenchymal stem cells (MSCs), leads to their attachment and proliferation on the PCL scaffold and provides a suitable environment for osteogenesis. In addition, biochemical tests showed that fibronectin leads to increased calcium deposition. The results also showed that alkaline phosphatase activity was significantly higher in the PCL scaffold coated with fibronectin than in the control groups (PCL scaffold group and tissue culture polystyrene (TCPS) group) (P<0.05). Also, the analysis of quantitative reverse transcription PCR (qRT-PCR) data showed that the relative expression of bone marker genes such as osteonectin (ON), osteocalcin (OC), RUNX family transcription factor 2 (RUNX2), and collagen type I alpha 1 (COL1) was much higher in the cells seeded on the PCL/Fn scaffold than in the other groups (P<0.05).

Conclusions: The results show that fibronectin has an increasing effect in accelerating bone formation and promising potential for use in bone tissue engineering.

背景:如今,通过组织工程替代受损器官或组织并修复损伤正引起人们的极大兴趣。一种潜在有效的骨重塑方法是将纳米纤维支架与细胞外基质(ECM)和生长因子相结合。如今,基于 PCL 的电纺支架已广泛应用于组织工程:在这项研究中,我们使用了一种涂有纤维连接蛋白(Fn)(一种无处不在的 ECM 糖蛋白)的电纺聚己内酯(PCL)支架,研究了这种支架在诱导脂肪间充质干细胞(AD-MSCs)成骨过程中的潜力:扫描电子显微镜(SEM)分析表明,纤连蛋白通过与间充质干细胞(MSCs)的膜受体结合,促使间充质干细胞在 PCL 支架上附着和增殖,为成骨提供了适宜的环境。此外,生化测试表明,纤连蛋白会导致钙沉积增加。结果还显示,涂有纤维连接蛋白的 PCL 支架的碱性磷酸酶活性明显高于对照组(PCL 支架组和组织培养聚苯乙烯(TCPS)组)(PConclusions:结果表明,纤维粘连蛋白在加速骨形成方面具有增效作用,有望用于骨组织工程。
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引用次数: 0
Acoustic vibration promotes in vitro expansion of human embryonic stem cells. 声学振动促进人类胚胎干细胞的体外扩增。
IF 1.5 Q4 CELL BIOLOGY Pub Date : 2024-06-15 eCollection Date: 2024-01-01 DOI: 10.62347/PJFC2708
Xiangyue Hu, Haoyun Duan, Dulei Zou, Chunxiao Dong, Yani Wang, Yao Wang, Zongren Li, Zongyi Li

Objectives: This study aimed to investigate the effect of acoustic vibration on the pluripotency of human embryonic stem cells (hESCs) and evaluate cell proliferation and self-renewal ability post-treatment.

Methods: The human ES cell line H1 was used for the experiments. hESCs were treated with an acoustic vibration device. Their proliferative ability was subsequently detected using a colony formation assay, while the expression of pluripotency-related markers was detected via immunofluorescence staining. Finally, changes in gene expression levels were examined using quantitative polymerase chain reaction (qPCR) in the presence of appropriate primers.

Results: Compared with normal cells in the control group, the morphology of experimental cells subjected to acoustic vibration did not significantly change. Contrastingly, the colony-forming efficiency of the experimental cells significantly increased. Immunofluorescence staining results showed the cells in experimental group were positive for the pluripotency markers NANOG, octamer-binding transcription factor 4 gene (OCT4), and SRY (sex determining region Y)-box 2 (SOX2). In addition, the expression levels of pluripotency genes NANOG, OCT4, SOX2, and Yes-associated protein (YAP)-related genes were up-regulated following acoustic vibration.

Conclusions: Our results revealed that acoustic vibration enhanced the proliferative ability of hESCs and increased the expression levels of NANOG, OCT4, SOX2, and YAP-related genes, indicating that acoustic vibration can optimize the self-renewal ability of hESCs and that the YAP signaling pathway may play a critical role in the functional process of acoustic vibration.

研究目的本研究旨在探讨声学振动对人类胚胎干细胞(hESCs)多能性的影响,并评估处理后细胞的增殖和自我更新能力:实验使用人类 ES 细胞株 H1。方法:实验采用人 ES 细胞系 H1,用声波振动装置处理 hESC,然后用集落形成试验检测其增殖能力,并通过免疫荧光染色检测多能性相关标记物的表达。最后,在适当引物的作用下,使用定量聚合酶链反应(qPCR)检测基因表达水平的变化:结果:与对照组的正常细胞相比,声学振动实验组细胞的形态没有明显变化。相反,实验组细胞的集落形成效率明显提高。免疫荧光染色结果显示,实验组细胞的多能性标志物NANOG、八聚体结合转录因子4基因(OCT4)和SRY(性别决定区Y)-box 2(SOX2)呈阳性。此外,多能性基因NANOG、OCT4、SOX2和Yes相关蛋白(YAP)相关基因的表达水平在声学振动后上调:我们的研究结果表明,声学振动增强了 hESCs 的增殖能力,提高了 NANOG、OCT4、SOX2 和 YAP 相关基因的表达水平,表明声学振动可以优化 hESCs 的自我更新能力,YAP 信号通路可能在声学振动的功能过程中发挥了关键作用。
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引用次数: 0
Advancements and challenges in stem/progenitor cell transplantation for dentin-pulp regeneration: a systematic review of animal studies (part I). 干细胞/祖细胞移植促进牙本质-牙髓再生的进展与挑战:动物研究系统综述(第一部分)。
IF 1.5 Q4 CELL BIOLOGY Pub Date : 2024-06-15 eCollection Date: 2024-01-01 DOI: 10.62347/HENE2422
Saeed Asgary, Mohammad Jafar Eghbal, Sayna Shamszadeh

Dentin-pulp regeneration through stem/progenitor cell transplantation represents a promising frontier in regenerative endodontics. This systematic review meticulously evaluates animal studies to investigate the efficacy of stem cell therapy in repairing/regenerating the dentine-pulp complex in mature/immature animal teeth. Employing a comprehensive electronic search of PubMed and Scopus databases up to October 2023, relevant English studies were identified/assessed. Evaluation parameters encompassed radiographic and histological assessments of dentin-pulp complex formation. Outcome measures included pulp-like and dentin-like tissues regeneration, apical healing, dentin thickening, apical closure, and dentinal bridge formation. The risk-of-bias assessment adhered to the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) guidelines. Out of 3250 identified articles, 23 animal experiments were included, categorized into regenerative procedures in mature teeth (n=11), regenerative procedures in immature teeth (n=4), and vital pulp therapy (n=8). Despite the promising potential, the bias in the included studies was high. Notably, Various scaffolds, and growth factors were employed, highlighting the heterogeneity across the studies. Dental pulp stem cells (DPSCs) and bone marrow stem cells, especially specific subfractions, demonstrated notable regenerative potential: hypoxic conditions and extracellular vesicles from preconditioned DPSCs enhanced regeneration, with considerations of cell fate. Donor age impacted regeneration, and challenges persisted in pulpotomy and direct pulp capping. Scaffold and growth factor choices influenced outcomes, underscoring the need for standardized strategies. Despite the promise, clinical viability faces hurdles, necessitating further investigation into adverse effects, optimized scaffolds, and regulatory considerations. This systematic review illuminates the potential of stem cell transplantation for dentin-pulp complex regeneration. The overall evidence quality, influenced by study heterogeneity and biases, underscores the need for cautious interpretation of findings. Future studies should refine methodologies and establish reliable histological parameters for meaningful advancements in dentin-pulp regeneration.

通过干细胞/祖细胞移植实现牙本质-牙髓再生是牙髓再生医学的一个前景广阔的前沿领域。这篇系统性综述对动物研究进行了细致评估,以研究干细胞疗法在修复/再生成熟/未成熟动物牙齿的牙本质-牙髓复合体方面的功效。通过对截至2023年10月的PubMed和Scopus数据库进行全面的电子检索,确定/评估了相关的英文研究。评估参数包括牙本质-牙髓复合体形成的放射学和组织学评估。结果测量包括牙髓样和牙本质样组织再生、根尖愈合、牙本质增厚、根尖封闭和牙本质桥形成。偏倚风险评估遵循了实验室动物实验系统审查中心(SYRCLE)的指导方针。在3250篇鉴定文章中,有23篇动物实验被纳入其中,分为成熟牙齿再生程序(11篇)、未成熟牙齿再生程序(4篇)和牙髓治疗(8篇)。尽管潜力巨大,但所纳入的研究偏差很大。值得注意的是,这些研究采用了不同的支架和生长因子,凸显了研究的异质性。牙髓干细胞(DPSCs)和骨髓干细胞,尤其是特定的亚组分,表现出显著的再生潜力:缺氧条件和预处理DPSCs细胞外囊泡增强了再生能力,同时考虑到细胞命运。供体年龄对再生有影响,牙髓切断术和直接牙髓覆盖术仍面临挑战。支架和生长因子的选择会影响结果,因此需要标准化的策略。尽管前景广阔,但临床可行性仍面临重重障碍,需要进一步研究不良反应、优化支架和监管因素。本系统综述阐明了干细胞移植在牙本质-牙髓复合体再生方面的潜力。受研究异质性和偏差的影响,总体证据质量突出表明,需要谨慎解释研究结果。未来的研究应完善方法,并建立可靠的组织学参数,以促进牙本质-牙髓再生。
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引用次数: 0
Advancing dentin-pulp regeneration: clinical perspectives and insights from stem/progenitor cell transplantation (part II). 推进牙本质-牙髓再生:干细胞/祖细胞移植的临床视角和启示(第二部分)。
IF 1.5 Q4 CELL BIOLOGY Pub Date : 2024-06-15 eCollection Date: 2024-01-01 DOI: 10.62347/BYPG4014
Sayna Shamszadeh, Mohammad Jafar Eghbal, Saeed Asgary

This systematic review evaluates clinical studies investigating regenerative endodontic procedures for mature/immature teeth utilizing stem cell transplantation. An electronic search of Scopus, PubMed, ISI Web Science, and Google Scholar was conducted up to January 2023. Outcome measures encompassed radiographic (periapical lesion, root length, apical foramen width, volume of the regenerated pulp) and clinical (post-operative pain, sensibility test) parameters. Among 3250 identified articles, five clinical studies were selected, comprising two randomized controlled trials (RCTs) for mature/immature teeth, and three case reports/series for mature teeth. Despite the promising potential, the included studies exhibited a notable risk of bias. The diversity in stem cells (e.g., dental pulp stem cells [DPSCs], umbilical cord mesenchymal stem cells [UC-MSCs]), scaffolds (Atecollagen, collagen membrane, platelet-poor plasma [PPP], leukocyte platelet-rich in fibrin [L-PRF]), and growth factors (granulocyte colony-stimulating factor [G-CSF]) emphasized the heterogeneity across interventions. In RCTs, DPSCs application increased root length and reduced apical foramen width in immature teeth, while UC-MSCs transplantation reduced apical lesions in mature teeth. Transplantation of DPSCs aggregates or UC-MSCs/PPP also elicited positive pulp responses and increased blood flow. In case reports/series, DPSCs application in teeth with irreversible pulpitis resulted in mineralization and increased the regenerated pulp' volume. Furthermore, transplantation of DPSCs with G-CSF/atelocollagen or L-PRF/collagen membrane led to positive pulp responses. While underscoring the potential of stem cell transplantation for regenerative endodontics in mature/immature teeth, the overall evidence quality and the limited number of available studies emphasize the need for cautious interpretation of results. Future well-designed clinical studies are essential to validate these findings further.

这篇系统性综述评估了利用干细胞移植对成熟/不成熟牙齿进行再生牙髓治疗的临床研究。对Scopus、PubMed、ISI Web Science和Google Scholar的电子检索截止到2023年1月。结果测量包括放射学参数(根尖周病变、牙根长度、根尖孔宽度、再生牙髓体积)和临床参数(术后疼痛、敏感性测试)。在已识别的 3250 篇文章中,选出了五项临床研究,包括两项针对成熟/不成熟牙齿的随机对照试验(RCT)和三项针对成熟牙齿的病例报告/系列研究。尽管这些研究很有潜力,但存在明显的偏差风险。干细胞(如牙髓干细胞[DPSCs]、脐带间充质干细胞[UC-MSCs])、支架(Atecollagen、胶原膜、贫血小板血浆[PPP]、富含纤维蛋白的白细胞血小板[L-PRF])和生长因子(粒细胞集落刺激因子[G-CSF])的多样性强调了不同干预措施的异质性。在临床试验中,应用 DPSCs 增加了未成熟牙的牙根长度并减少了根尖孔宽度,而 UC-MSCs 移植则减少了成熟牙的根尖病变。移植 DPSCs 聚合体或 UC-MSCs/PPP 还可引起积极的牙髓反应并增加血流量。在病例报告/系列报道中,在患有不可逆牙髓炎的牙齿中应用 DPSCs 可导致矿化,并增加再生牙髓的体积。此外,DPSCs与G-CSF/atelocollagen或L-PRF/collagen膜一起移植,可导致积极的牙髓反应。虽然强调了干细胞移植在成熟/未成熟牙齿牙髓再生中的潜力,但总体证据质量和可用研究数量有限,强调了谨慎解释结果的必要性。未来精心设计的临床研究对进一步验证这些发现至关重要。
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American journal of stem cells
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