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The Potential of Neonatal Organ Donation in Central Sweden. 瑞典中部新生儿器官捐献的潜力。
IF 3.2 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-01-01 DOI: 10.1177/09636897241303269
Emil Bluhme, Ewa Henckel, Boubou Hallberg, Carl Jorns

Pediatric organ transplant recipients have a higher risk for wait list mortality due to the scarcity of size matched organs. Neonatal organ donation could potentially ameliorate the discrepancy but is currently not implemented in Sweden. This study aims to evaluate the potential of neonatal organ donation in central Sweden using a standardized protocol with organ specific criteria. Data on 2,061 neonates who deceased in central Sweden from 2006 to 2016 were collected; 308 neonates met criteria for possible donation. Medical records of all possible donors were reviewed, identifying 85 potential donors. Main cause of death was hypoxic ischemic encephalopathy 47% (n = 40). Median weight was 2,355 (IQR: 1,953) g, with 31% receiving inotropic support. Median creatinine of 72 (IQR: 67) µmol/l, urine production 3 (IQR: 2.2) ml/kg/h, ALT 0.51 (IQR: 1.5) µkat/l, and AST 1.7 (IQR: 3.1) µkat/l. Criteria for kidney donation was met in 39 potential neonatal, 29 for liver and 18 for heart, corresponding to a potential increase of 1.9, 1.4, and 0.9 donors PMP per year, respectively. In total, 16 neonates had a catastrophic neurological injury in combination with lack of brainstem reflexes, indicating plausibility of donation after brain death. Expanding organ donation into the neonatal period in Sweden could lead to an increase in organs available for transplant.

由于缺乏大小匹配的器官,儿童器官移植受者在等待名单上死亡的风险更高。新生儿器官捐赠可能会改善这种差异,但目前在瑞典尚未实施。本研究旨在评估瑞典中部新生儿器官捐赠的潜力,使用具有器官特定标准的标准化协议。收集了2006年至2016年在瑞典中部死亡的2061名新生儿的数据;308名新生儿符合可能的捐献标准。审查了所有可能捐助者的医疗记录,确定了85名潜在捐助者。死亡主要原因为缺氧缺血性脑病,占47% (n = 40)。中位体重为2355 (IQR: 1953) g, 31%接受肌力支持。中位肌酐72 (IQR: 67)µmol/l,尿生成3 (IQR: 2.2) ml/kg/h, ALT 0.51 (IQR: 1.5)µkat/l, AST 1.7 (IQR: 3.1)µkat/l。39名潜在新生儿符合肾脏捐献标准,29名符合肝脏捐献标准,18名符合心脏捐献标准,对应于每年分别增加1.9、1.4和0.9名捐赠者PMP。总共有16名新生儿发生了灾难性的神经损伤,并伴有脑干反射不足,这表明脑死亡后捐赠是合理的。在瑞典,将器官捐赠扩大到新生儿期可能会导致可供移植的器官增加。
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引用次数: 0
Stem cell therapy for inherited retinal diseases: Trends and insights from 2000 to 2024. 干细胞治疗遗传性视网膜疾病:从2000年到2024年的趋势和见解。
IF 3.2 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-01-01 Epub Date: 2025-12-10 DOI: 10.1177/09636897251400835
Jinyi Long, Ziyang Xu, Ping Hu, Yuhong Ye, Da Long

Stem cell therapy has emerged as a promising strategy for inherited retinal diseases (IRDs), yet its global research trajectory has not been systematically mapped. This study analyzes publication trends, leading contributors, and thematic evolution of IRD stem cell therapy research from 2000 to 2024. Publications were retrieved from the Web of Science Core Collection and analyzed with CiteSpace and VOSviewer. We identified 1060 articles with a steady rise in annual output. The United States and China were the most prolific countries; University College London and the University of Iowa were major institutions; and key outlets included Stem Cell Research & Therapy, Investigative Ophthalmology & Visual Science, and Cell Transplantation. Keyword and co-citation analyses reveal a clear trajectory: early emphasis on stem cell-derived retinal pigment epithelium transplantation for photoreceptor rescue, subsequent expansion to photoreceptor precursor and retinal organoid replacement, and recent movement toward early clinical translation. Persisting challenges include long-term graft survival, functional integration, and immune compatibility. Overall, this bibliometric roadmap clarifies how the field is transitioning from foundational studies to translational application and highlights priorities for interdisciplinary collaboration to accelerate clinical advancement.

干细胞治疗已成为一种治疗遗传性视网膜疾病(IRDs)的有前景的策略,但其全球研究轨迹尚未系统绘制。本研究分析了2000年至2024年IRD干细胞治疗研究的出版趋势、主要贡献者和主题演变。出版物从Web of Science核心馆藏中检索,并使用CiteSpace和VOSviewer进行分析。我们确定了年产量稳步增长的品种1060种。美国和中国是最多产的国家;伦敦大学学院和爱荷华大学是主要院校;《干细胞研究与治疗》、《眼科学与视觉科学研究》、《细胞移植》等重点期刊。关键词和共引分析揭示了一个清晰的发展轨迹:早期强调干细胞来源的视网膜色素上皮移植用于光感受器的拯救,随后扩展到光感受器前体和视网膜类器官替代,最近转向早期临床转化。持续存在的挑战包括移植物的长期存活、功能整合和免疫相容性。总体而言,这一文献计量学路线图阐明了该领域如何从基础研究过渡到转化应用,并强调了跨学科合作的优先事项,以加速临床进展。
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引用次数: 0
Correlation between the expression of soluble BCMA and short-term/long-term curative effect and survival outcomes of anti-BCMA CAR-T cell therapy in relapsed/refractory multiple myeloma. 可溶性BCMA表达与抗BCMA CAR-T细胞治疗复发/难治性多发性骨髓瘤的短期/长期疗效和生存结局的相关性
IF 3.2 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-01-01 Epub Date: 2025-09-20 DOI: 10.1177/09636897251374203
Mingwei Fu, Siyan Niu, Can Liu, Juan Mu, Shuquan Gao, Gang An, Rui Cui, Qi Deng

This study aimed to investigate whether soluble B-cell maturation antigen (sBCMA) levels could be predictive biomarker for short-term and long-term therapeutic efficacy and survival outcomes following anti-BCMA CAR-T cell therapy in relapsed/refractory multiple myeloma (R/R MM). We enrolled 29 R/R MM patients who received anti-BCMA CAR-T cell therapy. In short-term observation, proportion of MM cells, expression of B-cell maturation antigen (BCMA) and sBCMA in bone marrow (BM) were evaluated, along with adverse events, correlation between sBCMA levels and short-term efficacy or survival outcomes were evaluated. In long-term observation, expressions of sBCMA were observed up to 24 months after therapy or until disease progression again in patients who achieved an objective response (ORR). Progression-free survival (PFS), overall survival (OS), correlation between sBCMA levels, and long-term outcomes were analyzed. In short-term observation, high expressions of sBCMA in BM were associated with poor efficacy of CAR-T cell therapy, while the proportion of MM cells in BM and BCMA expression in MM cells were not associated with poor efficacy of therapy. After 2 months of infusion, sBCMA levels decreased significantly, especially in patients who obtained ORR. In long-term follow-up, for patients who achieved ORR, the sBCMA levels significantly increased again when their disease progressed once more. Notably, R/R MM patients with extramedullary disease (EMD) demonstrated a higher likelihood of disease progression again. In patients achieved ORR, peaks of CAR-T cells correlated with proportion of MM cells, not with BCMA and sBCMA expression. Additionally, sBCMA levels were independent of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) severity. We suggest that sBCMA levels in BM might serve as a predictive biomarker for anti-BCMA CAR-T cell therapy efficacy prior to treatment and for disease progression during long-term monitoring. The trail register name is China Clinical Trial Register. URL are https://www.chictr.org.cn/bin/project/edit?pid=28999 and https://www.chictr.org.cn/bin/project/edit?pid=53962. Registration numbers are ChiCTR1800017051 and ChiCTR2000033925.

本研究旨在探讨可溶性b细胞成熟抗原(sBCMA)水平是否可以作为复发/难治性多发性骨髓瘤(R/R MM)抗bcma CAR-T细胞治疗后短期和长期治疗疗效和生存结果的预测性生物标志物。我们招募了29例接受抗bcma CAR-T细胞治疗的R/R MM患者。在短期观察中,评估MM细胞比例、骨髓中b细胞成熟抗原(BCMA)和sBCMA的表达,以及不良事件、sBCMA水平与短期疗效或生存结局的相关性。在长期观察中,sBCMA的表达在治疗后24个月或在达到客观缓解(ORR)的患者中再次进展。分析无进展生存期(PFS)、总生存期(OS)、sBCMA水平与长期预后的相关性。在短期观察中,BM中sBCMA的高表达与CAR-T细胞治疗效果差相关,而BM中MM细胞的比例和MM细胞中BCMA的表达与治疗效果差无关。输注2个月后,sBCMA水平显著下降,特别是在获得ORR的患者中。在长期随访中,对于达到ORR的患者,当疾病再次进展时,sBCMA水平再次显著升高。值得注意的是,R/R MM合并髓外疾病(EMD)的患者再次出现疾病进展的可能性更高。在达到ORR的患者中,CAR-T细胞峰值与MM细胞比例相关,而与BCMA和sBCMA表达无关。此外,sBCMA水平与细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS)严重程度无关。我们认为BM中的sBCMA水平可以作为治疗前抗bcma CAR-T细胞治疗效果和长期监测期间疾病进展的预测性生物标志物。试验注册名称为中国临床试验注册。网址分别为https://www.chictr.org.cn/bin/project/edit?pid=28999和https://www.chictr.org.cn/bin/project/edit?pid=53962。注册号为ChiCTR1800017051和ChiCTR2000033925。
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引用次数: 0
Key mediators of the efficacy of mesenchymal stem cells on in vivo disease models. 间充质干细胞作用于体内疾病模型的关键介质。
IF 3.2 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-01-01 Epub Date: 2025-06-25 DOI: 10.1177/09636897251348566
Kentaro Nakamura

Mesenchymal stem cells (MSCs) are considered to be effective treatments for various diseases, and a wide variety of clinical studies have been performed worldwide. However, substantial obstacles remain before they can be approved and disseminated as treatments. A major bottleneck is the elucidation of their mechanisms of action, and the molecules that are essential for their efficacy have not been fully characterized. In this paper, I review the studies that attempted to identify the key mediators of MSCs that are involved in their effects on disease using in vivo models. More specifically, studies are discussed in which reductions in the efficacy of MSCs in animal models of disease were induced by the absence of key mediators. The target diseases were lung, joint, cerebral nerve, or cardiac diseases and graft-versus-host disease (GVHD). The following molecules were identified and are discussed herein: TSG-6, VEGF, KGF, HGF, claudin-4, ANXA1, MANF, PYCR1, integrin β1, PDGFRβ, type-II collagen, CD151, TIMP3, TGF-β1, BDNF, COX-2, Botch, IL-1β, CTRP3, CXCR4, miR-34c, FSTL1, IDO, iNOS, IFNγR1, PGES, Chi3l1, and IL-6. These are key mediators of the efficacy of MSCs in vivo.

间充质干细胞(MSCs)被认为是治疗多种疾病的有效方法,在世界范围内进行了各种各样的临床研究。然而,在它们作为治疗方法获得批准和传播之前,仍存在重大障碍。一个主要的瓶颈是对其作用机制的阐明,以及对其功效至关重要的分子尚未完全表征。在本文中,我回顾了试图利用体内模型确定MSCs的关键介质参与其对疾病的影响的研究。更具体地说,研究中讨论了由于缺乏关键介质而导致动物疾病模型中MSCs功效降低的研究。目标疾病是肺、关节、脑神经或心脏疾病和移植物抗宿主病(GVHD)。我们鉴定并讨论了以下分子:TSG-6、VEGF、KGF、HGF、cladin -4、ANXA1、MANF、PYCR1、整合素β1、PDGFRβ、ii型胶原、CD151、TIMP3、TGF-β1、BDNF、COX-2、Botch、IL-1β、CTRP3、CXCR4、miR-34c、FSTL1、IDO、iNOS、IFNγR1、PGES、Chi3l1和IL-6。这些是体内MSCs功效的关键介质。
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引用次数: 0
Cellular therapy for locomotor function: Translating potential into practice. 运动功能的细胞疗法:将潜能转化为实践。
IF 3.2 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-01-01 Epub Date: 2025-10-09 DOI: 10.1177/09636897251375325
Munehisa Shinozaki

This editorial introduces a special issue on cell-based therapies for disorders affecting locomotor function. The articles span a range of approaches, including methods to enhance immunological compatibility in induced pluripotent stem cell transplantation, as well as clinical and preclinical investigations using mesenchymal stem cells for the treatment of osteoarthritis. These studies address different therapeutic strategies and stages of development, reflecting ongoing efforts to translate basic research into safe and practical treatments for locomotor conditions.

这篇社论介绍了一个特殊的问题,细胞为基础的治疗疾病影响运动功能。这些文章涵盖了一系列的方法,包括在诱导多能干细胞移植中增强免疫相容性的方法,以及使用间充质干细胞治疗骨关节炎的临床和临床前研究。这些研究涉及不同的治疗策略和发展阶段,反映了将基础研究转化为安全实用的运动条件治疗的持续努力。
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引用次数: 0
Advanced medical treatments for hair loss. 先进的治疗脱发的药物。
IF 3.2 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-01-01 Epub Date: 2025-10-22 DOI: 10.1177/09636897251382318
Kwanrudee Kaewmungkun, Somruethai Kaisang, Nattida Yokhaphachon, Rangsun Parnpai

Patients with hair-loss experience stress and a loss of confidence. Several factors contribute to hair loss, including aging, androgen hormone effects, genetics, and diseases. Normally, physicians treat hair loss using medications such as minoxidil and finasteride. However, these treatments are associated with side effects and some limitations. Currently, hair transplantation is the most efficient technique; however, it requires the use of numerous hair grafts. Stem cell and hair follicle cell (HFC) treatments have been developed for hair-loss treatment. Previously, stem cell and HFC therapies have been shown to promote hair development, prolong the anagen phase, and increase hair diameter and density. In addition, growth factors and extracellular vesicles (EVs) are important for prolonging the anagen phase, improving hair follicle health, and reducing dihydrotestosterone effects. Furthermore, gene therapy and tissue engineering have also been developed as treatments for hair loss. In this review, we discuss (i) the basic knowledge and molecular signaling relevant to hair regeneration and (ii) advanced technology medical treatments for hair loss (stem cells, HFCs, growth factor, EVs, gene therapy, and tissue engineers).

脱发患者会经历压力和自信心的丧失。有几个因素会导致脱发,包括衰老、雄激素的影响、遗传和疾病。通常,医生使用米诺地尔和非那雄胺等药物治疗脱发。然而,这些治疗都有副作用和一些局限性。目前,头发移植是最有效的技术;然而,它需要使用大量的头发移植。干细胞和毛囊细胞(HFC)治疗已经发展成为治疗脱发的方法。此前,干细胞和HFC疗法已被证明可以促进头发发育,延长毛发生长阶段,增加头发直径和密度。此外,生长因子和细胞外囊泡(EVs)在延长毛发生长期、改善毛囊健康和减少双氢睾酮作用方面也很重要。此外,基因疗法和组织工程也已发展成为治疗脱发的方法。在这篇综述中,我们讨论了(i)与头发再生相关的基础知识和分子信号,(ii)治疗脱发的先进技术(干细胞、氢氟碳化物、生长因子、ev、基因治疗和组织工程师)。
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引用次数: 0
From risk perception to action: A qualitative study of self-management in hematopoietic stem cell transplant patients. 从风险认知到行动:造血干细胞移植患者自我管理的定性研究。
IF 3.2 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-01-01 Epub Date: 2025-12-04 DOI: 10.1177/09636897251393308
Xiaoyan Yu, Zhizi Xiao, Xuee Li, Huan Yuan

A descriptive qualitative study was conducted to explore risk perception, self-management challenges, and coping strategies among Chinese hematopoietic stem cell transplantation (HSCT) patients, using the Health Action Process Approach (HAPA) as the guiding framework. Purposive sampling, based on the principle of information power, was employed to recruit 20 HSCT patients from a hospital in south-central China between May and August 2024. The HAPA model informed the development of semi-structured interview questions, and the data were analyzed using a combination of thematic analysis and framework analysis. The findings indicate that both risk perception and self-efficacy play a critical role in motivating patient engagement in self-management. Main barriers to self-management included difficulties in symptom control, lifestyle modification, psychological adjustment, and healthcare-related financial burdens. Effective coping strategies reported by participants involved the use of digital tools, seeking professional medical advice, maintaining self-management journals, and drawing on family and social support networks. In clinical practice, healthcare professionals may capitalize on the heightened risk perception and self-efficacy during the peri-transplant period to promote the transition from risk perception to actionable self-management behaviors. In contrast, during the early post-discharge phase, when both risk perception and self-efficacy tend to decline, tailored support systems and resource allocation are helpful for maintaining the transition from risk perception to self-management action.

以健康行动过程方法(HAPA)为指导框架,对中国造血干细胞移植(HSCT)患者的风险认知、自我管理挑战和应对策略进行了描述性定性研究。采用目的性抽样,基于信息力量原则,于2024年5月至8月在中国中南部某医院招募20例HSCT患者。HAPA模型为半结构化访谈问题的开发提供了信息,并采用主题分析和框架分析相结合的方法对数据进行了分析。研究结果表明,风险感知和自我效能感在激励患者参与自我管理中起着关键作用。自我管理的主要障碍包括症状控制困难、生活方式改变、心理调整和卫生保健相关的经济负担。参与者报告的有效应对策略包括使用数字工具、寻求专业医疗建议、维护自我管理日志以及利用家庭和社会支持网络。在临床实践中,医疗保健专业人员可以利用移植围期间风险感知和自我效能的增强来促进从风险感知到可操作的自我管理行为的转变。而在出院初期,风险感知和自我效能感都趋于下降,有针对性的支持系统和资源配置有助于维持风险感知向自我管理行动的转变。
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引用次数: 0
Impact of posaconazole tablets for secondary prophylaxis on drug interactions in haploidentical allogeneic stem cell transplantation: A single-arm, open-label, prospective study. 泊沙康唑片用于二级预防对单倍异体干细胞移植中药物相互作用的影响:一项单臂、开放标签、前瞻性研究
IF 3.2 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-01-01 Epub Date: 2025-10-29 DOI: 10.1177/09636897251378570
Xiaoning Wang, Yuqi Wang, Pengcheng He

Posaconazole (POS) tablets were approved for prophylaxis of invasive fungal disease (IFD) in patients with hematological disorders undergoing haploidentical allogeneic stem cell transplantation (haplo-HSCT). There is limited research on drug-drug interactions (DDIs) between POS, cyclosporine A (CsA), and mycophenolate mofetil (MMF), as well as the impact of POS on acute graft versus host disease (aGVHD) in haplo-HSCT patients receiving POS for secondary antifungal prophylaxis (SAP). This study aims to investigate the DDI between POS, CsA, and MMF, as well as the incidence of aGVHD in haplo-HSCT patients with prior-IFD. This is a single-arm, open-label, prospective trial. Plasma concentrations of POS, mycophenolic acid (MPA), and CsA were monitored within 30 days post-transplantation. In addition, the incidences of aGVHD and IFD were observed. Forty-six patients with prior-IFD were enrolled. POS reached a steady state by week 2, with the mean through blood concentration (TBC) of 0.54 ± 0.07 μg/mL. MPA achieved target levels by week 3 without dose adjustment, with a mean TBC of 0.84 ± 0.08 mg/L. The CsA TBC levels required individualized dose modifications. The incidences of grade II-IV and grade III-IV aGVHD were 47.83% and 21.74%, respectively. The breakthrough rate of SAP was 4.35% at 100 days and 10.86% at 6 months. The conclusions indicate that POS tablets do not require dose adjustments for MMF; however, CsA dosing must be individualized. POS tablets appear to be effective and well-tolerated for SAP in haplo-HSCT (the Chinese Clinical Trial Registry: www.chictr.org.cn (ChiCTR2200059472)).

泊沙康唑(POS)片被批准用于接受单倍同种异体干细胞移植(haploo - hsct)的血液病患者预防侵袭性真菌病(IFD)。关于POS、环孢素A (CsA)和霉酚酸酯(MMF)之间的药物-药物相互作用(ddi),以及POS对接受POS进行二次抗真菌预防(SAP)的单倍hsct患者急性移植物抗宿主病(aGVHD)的影响的研究有限。本研究旨在探讨POS、CsA和MMF之间的DDI,以及既往ifd的单倍hsct患者aGVHD的发生率。这是一项单臂、开放标签、前瞻性试验。移植后30天内监测血浆中POS、霉酚酸(MPA)和CsA的浓度。同时观察aGVHD和IFD的发生率。纳入46例既往ifd患者。到第2周,POS达到稳定状态,平均血药浓度(TBC)为0.54±0.07 μg/mL。在不调整剂量的情况下,MPA在第3周达到目标水平,平均TBC为0.84±0.08 mg/L。CsA TBC水平需要个体化剂量调整。II-IV级和III-IV级aGVHD的发生率分别为47.83%和21.74%。100天SAP突破率为4.35%,6个月突破率为10.86%。结论表明,POS片不需要调整MMF剂量;然而,CsA的剂量必须个体化。POS片剂似乎对单倍hsct患者的SAP有效且耐受性良好(中国临床试验注册:www.chictr.org.cn (ChiCTR2200059472))。
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引用次数: 0
Enhancing female fertility by biomaterial-based regeneration of uterine tubes. 基于生物材料的输卵管再生提高女性生育能力。
IF 3.2 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-01-01 Epub Date: 2025-11-30 DOI: 10.1177/09636897251397047
Martina Culenova, Maria Kleinova

Tubal factor infertility remains a major cause of female reproductive dysfunction. Current therapeutic options, such as surgical repair or in vitro fertilization, only bypass but do not restore the dysfunctional uterine tube. Recent advances in tissue engineering and regenerative medicine (TERM) highlight biomaterials and organoid systems as promising tools to regenerate oviductal tissue and thus support natural conception. The manuscript comprehensively reviews 42 studies focused solely on TERM of the uterine tubes. Current status of uterine tube tissue engineering demonstrates that natural polymers, including collagen and decellularized extracellular matrix, provide biocompatible scaffolds capable of mimicking native extracellular environments. Synthetic polymers enable adjustment of mechanical properties and reproducibility, while hydrogels offer a biomimetic 3D microenvironment that supports epithelial differentiation, angiogenesis, and embryo development. Moreover, uterine tube-derived organoids, in which the polymeric component plays a crucial role, provide physiologically relevant in vitro models for studying pathology, drug testing, and translational applications. Recent advances in 3D bioprinting and magnetic bioprinting have enabled the development of artificial uterine tube models that better mimic native tissue architecture and cell organization. These findings underscore the translational potential of biomaterial-based strategies for uterine tube regeneration. Their integration into reproductive medicine may offer novel therapeutic avenues for restoring tubal function, improving fertility outcomes, and advancing patient-specific approaches in the management of female infertility.

输卵管性不孕仍是女性生殖功能障碍的主要原因。目前的治疗选择,如手术修复或体外受精,只能绕道而不能恢复功能失调的输卵管。组织工程和再生医学(TERM)的最新进展突出了生物材料和类器官系统作为再生输卵管组织的有前途的工具,从而支持自然受孕。本文全面回顾了42项研究,重点是输卵管的TERM。输卵管组织工程的现状表明,天然聚合物,包括胶原蛋白和脱细胞细胞外基质,提供了能够模拟天然细胞外环境的生物相容性支架。合成聚合物可以调节机械性能和可重复性,而水凝胶提供仿生3D微环境,支持上皮分化、血管生成和胚胎发育。此外,聚合物成分在子宫输卵管衍生的类器官中起着至关重要的作用,为研究病理、药物测试和转化应用提供了生理相关的体外模型。生物3D打印和磁性生物打印的最新进展使人工输卵管模型的发展能够更好地模拟天然组织结构和细胞组织。这些发现强调了基于生物材料的输卵管再生策略的转化潜力。它们与生殖医学的结合可能为恢复输卵管功能、改善生育结果和推进女性不孕症的患者特异性治疗提供新的治疗途径。
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引用次数: 0
Selective TCRαβ+ and CD45RA+ T-cell depletion of hematopoietic stem cell graft: An analysis on factors that affect depletion performance. 造血干细胞移植物选择性TCRαβ+和CD45RA+ t细胞耗竭:影响耗竭性能的因素分析。
IF 3.2 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-01-01 Epub Date: 2025-05-08 DOI: 10.1177/09636897251336965
Chieh Hwee Ang, Gina Gan, Ren How Ho, Kee Khiang Heng, Yeh Ching Linn

Selective depletion of TCRαβ+ and CD45RA+ subsets of apheresed hematopoietic progenitor cells, HPC(A), enables haploidentical hematopoietic stem cell transplant (haplo-HSCT) by circumventing risks of graft-versus-host disease. Here, we analyze our institution's large series of ex vivo T-cell depletion processes to review procedure performance and explore factors that affect depletion efficiency and graft composition. Over 6 years, 91 haploidentical donors underwent peripheral blood CD34+ stem cell mobilization with granulocyte-colony stimulating factor, with 12 (13%) receiving additional pre-emptive plerixafor. HPC(A) was split into two fractions for TCRαβ and CD45RA depletion with the CliniMACS PLUS device. TCRαβ depletion resulted in a median 4.3 (interquartile range, 4.1-4.5) log reduction, with CD34 recovery at 98% (94%-103%) and TCRγδ+ cell recovery at 89% (74%-98%). CD45RA depletion resulted in a median 4.8 (4.3-5.2) log reduction, with CD3+/CD45RO+ cell recovery at 41% (34%-47%) and CD34 recovery at 58% (51%-68%). TCRαβ depletion efficiency was maintained even when total nucleated cell counts exceeded the maximal specified number, provided the target fraction was within capacity of the depletion kit. Platelet contamination did not affect depletion efficacy or CD34 recovery. Age increases the proportion of CD45RO+ memory cells and TCRαβ subset in HPC(A), while plerixafor increases the latter. Although statistically significant correlation exists between pre-depletion cell composition and depletion performance for some cell subsets, the post-depletion product still met pre-specified threshold without being affected to a clinically relevant extent, over a wide range of input cell numbers. Such robustness of the depletion systems is critical for successful performance of haplo-HSCT.

选择性地去除非造血祖细胞(HPC)的TCRαβ+和CD45RA+亚群,通过规避移植物抗宿主病的风险,实现单倍体相同的造血干细胞移植(haploi - hsct)。在这里,我们分析了我们机构的大量体外t细胞耗竭过程,以审查程序性能并探索影响耗竭效率和移植物成分的因素。在6年多的时间里,91名单倍体捐赠者接受了粒细胞集落刺激因子的外周血CD34+干细胞动员,其中12名(13%)接受了额外的先发制人的plerixafor。使用CliniMACS PLUS装置将HPC(A)分成两部分用于TCRαβ和CD45RA的消耗。TCRαβ缺失导致中位4.3(四分位数范围,4.1-4.5)对数降低,CD34回收率为98% (94%-103%),TCRγδ+细胞回收率为89%(74%-98%)。CD45RA缺失导致中位4.8(4.3-5.2)对数降低,CD3+/CD45RO+细胞回收率为41% (34%-47%),CD34回收率为58%(51%-68%)。即使有核细胞总数超过最大规定数,只要目标分数在耗尽试剂盒的容量范围内,TCRαβ的耗尽效率也保持不变。血小板污染不影响耗竭疗效或CD34回收率。年龄增加了HPC中CD45RO+记忆细胞和TCRαβ亚群的比例(A),而多利沙素增加了后者。尽管在一些细胞亚群中,耗竭前的细胞组成与耗竭性能之间存在统计学上显著的相关性,但在大量输入细胞数量的情况下,耗竭后的产物仍然满足预先规定的阈值,而不会受到临床相关程度的影响。这种损耗系统的鲁棒性对于单倍hsct的成功执行至关重要。
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Cell Transplantation
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