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Decellularized extracellular matrix mediates tissue construction and regeneration

《医学前沿（英文）》 2022年第16卷第1期页码 56-82 doi: 10.1007/s11684-021-0900-3

摘要： Contributing to organ formation and tissue regeneration, extracellular matrix (ECM) constituents provide tissue with three-dimensional (3D) structural integrity and cellular-function regulation. Containing the crucial traits of the cellular microenvironment, ECM substitutes mediate cell–matrix interactions to prompt stem-cell proliferation and differentiation for 3D organoid construction in vitro or tissue regeneration in vivo. However, these ECMs are often applied generically and have yet to be extensively developed for specific cell types in 3D cultures. Cultured cells also produce rich ECM, particularly stromal cells. Cellular ECM improves 3D culture development in vitro and tissue remodeling during wound healing after implantation into the host as well. Gaining better insight into ECM derived from either tissue or cells that regulate 3D tissue reconstruction or organ regeneration helps us to select, produce, and implant the most suitable ECM and thus promote 3D organoid culture and tissue remodeling for in vivo regeneration. Overall, the decellularization methodologies and tissue/cell-derived ECM as scaffolds or cellular-growth supplements used in cell propagation and differentiation for 3D tissue culture in vitro are discussed. Moreover, current preclinical applications by which ECM components modulate the wound-healing process are reviewed.

关键词： decellularized extracellular matrix 3D culture organoids tissue repair

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Stem cell niches and endogenous electric fields in tissue repair

null

《医学前沿（英文）》 2011年第5卷第1期页码 40-44 doi: 10.1007/s11684-011-0108-z

摘要：

Adult stem cells are responsible for homeostasis and repair of many tissues. Endogenous adult stem cells reside in certain regions of organs, known as the stem cell niche, which is recognized to have an important role in regulating tissue maintenance and repair. In wound healing and tissue repair, stem cells are mobilized and recruited to the site of wound, and participate in the repair process. Many regulatory factors are involved in the stem cell-based repair process, including stem cell niches and endogenous wound electric fields, which are present at wound tissues and proved to be important in guiding wound healing. Here we briefly review the role of stem cell niches and endogenous electric fields in tissue repair, and hypothesize that endogenous electric fields become part of stem cell niche in the wound site.

关键词： stem cell stem cell niche electric field tissue repair

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组织再生：梦想、希望和挑战

付小兵

《中国工程科学》 2009年第11卷第10期页码 122-128

摘要：

组织再生是21世纪生物学和医学领域研究的重点和热点。在回顾再生医学研究历史的基础上，概要介绍了组织再生所涉及的关键科学问题、重大需求以及部分已经取得的重要进展，并对将来的发展进行了展望。

关键词：损伤组织修复再生

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Insights into optimizing exosome therapies for acute skin wound healing and other tissue repair

《医学前沿（英文）》 2024年第18卷第2期页码 258-284 doi: 10.1007/s11684-023-1031-9

摘要： Exosome therapy holds great promise as a novel approach to improve acute skin wound healing. This review provides a comprehensive overview of the current understanding of exosome biology and its potential applications in acute skin wound healing and beyond. Exosomes, small extracellular vesicles secreted by various stem cells, have emerged as potent mediators of intercellular communication and tissue repair. One advantage of exosome therapy is its ability to avoid potential risks associated with stem cell therapy, such as immune rejection or stem cells differentiating into unwanted cell types. However, further research is necessary to optimize exosome therapy, not only in the areas of exosome isolation, characterization, and engineering, but also in determining the optimal dose, timing, administration, and frequency of exosome therapy. Thus, optimization of exosome therapy is critical for the development of more effective and safer exosome-based therapies for acute skin wound healing and other diseases induced by cancer, ischemia, or inflammation. This review provides valuable insights into the potential of exosome therapy and highlights the need for further research to optimize exosome therapy for clinical use.

关键词： exosomes stem cells therapeutic impact skin wound healing

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生物材料在心脏修复和再生中的应用 Review

Zhi Cui,Baofeng Yang,Ren-Ke Li

《工程（英文）》 2016年第2卷第1期页码 141-148 doi: 10.1016/J.ENG.2016.01.028

摘要：

心血管疾病是全世界主要致死原因之一。人们对新的干预性治疗手段的需求与日俱增。虽然药物和手术治疗极大地改善了心血管疾病患者的生活质量，但人们还是需要价格更便宜、副作用更小的治疗手段。天然和合成生物材料无论是作为给药载体，还是替代支架的细胞外基质，在心脏修复和再生中都展现出巨大的潜力。本文探讨了目前治疗心血管疾病的几种方式和应用于上述疾病干预性治疗的生物材料；着重研究了导电聚合物在纠正局部缺血性心脏病引发的传导异常及其在心脏起搏器中应用的可能性，以改善心肌梗死状态下的传导路径。

关键词：心肌梗死心脏再生生物材料组织工程干细胞

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Generation and repair of AID-initiated DNA lesions in B lymphocytes

null

《医学前沿（英文）》 2014年第8卷第2期页码 201-216 doi: 10.1007/s11684-014-0324-4

摘要：

Activation-induced deaminase (AID) initiates the secondary antibody diversification process in B lymphocytes. In mammalian B cells, this process includes somatic hypermutation (SHM) and class switch recombination (CSR), both of which require AID. AID induces U:G mismatch lesions in DNA that are subsequently converted into point mutations or DNA double stranded breaks during SHM/CSR. In a physiological context, AID targets immunoglobulin (Ig) loci to mediate SHM/CSR. However, recent studies reveal genome-wide access of AID to numerous non-Ig loci. Thus, AID poses a threat to the genome of B cells if AID-initiated DNA lesions cannot be properly repaired. In this review, we focus on the molecular mechanisms that regulate the specificity of AID targeting and the repair pathways responsible for processing AID-initiated DNA lesions.

关键词： class switch recombination somatic hypermutation activation-induced deaminase DNA repair genomic instability

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A distinct “repair” role of regulatory T cells in fracture healing

《医学前沿（英文）》 2024年第18卷第3期页码 516-537 doi: 10.1007/s11684-023-1024-8

摘要： Regulatory T cells (Tregs) suppress immune responses and inflammation. Here, we described the distinct nonimmunological role of Tregs in fracture healing. The recruitment from the circulation pool, peripheral induction, and local expansion rapidly enriched Tregs in the injured bone. The Tregs in the injured bone displayed superiority in direct osteogenesis over Tregs from lymphoid organs. Punctual depletion of Tregs compromised the fracture healing process, which leads to increased bone nonunion. In addition, bone callus Tregs showed unique T-cell receptor repertoires. Amphiregulin was the most overexpressed protein in bone callus Tregs, and it can directly facilitate the proliferation and differentiation of osteogenic precursor cells by activation of phosphatidylinositol 3-kinase/protein kinase B signaling pathways. The results of loss- and gain-function studies further evidenced that amphiregulin can reverse the compromised healing caused by Treg dysfunction. Tregs also enriched in patient bone callus and amphiregulin can promote the osteogenesis of human pre-osteoblastic cells. Our findings indicate the distinct and nonredundant role of Tregs in fracture healing, which will provide a new therapeutic target and strategy in the clinical treatment of fractures.

关键词： regulatory T cells fracture healing amphiregulin non-union osteogenesis

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用于关节软骨组织工程的功能化水凝胶 Review

周良彬, 郭鹏, Matteo D’Este, 童文学, 许建坤, 姚昊, Martin J. Stoddart, Gerjo J.V.M. van Osch, 何其威, 李真, 秦岭

《工程（英文）》 2022年第13卷第6期页码 71-90 doi: 10.1016/j.eng.2022.03.008

摘要：

关节软骨是位于关节骨表面的一种无血管且富有弹性的结缔组织。软骨损伤常出现于年轻人和经常从事体育活动的人的膝盖中，由于缺乏合适的基于组织工程的人工基质，目前针对软骨损伤的治疗，特别是对于全层软骨缺损和骨-软骨界面的治疗方式，依旧无法充分替代或再生受损的软骨。随着关节软骨组织工程研发的飞速进展，功能化水凝胶因其自身良好的生物力学性能、含水量、膨胀系数、细胞相容性、生物可降解性和润滑能力，而逐渐涌现成为富有前景的软骨基质替代物。功能化水凝胶可以被合理的设计和根据其理化性能被便捷的调整来模拟软骨的胞外基质。本综述先简要介绍了关节软骨的组成、结构、功能以及关节软骨损伤，然后全面回顾了功能化水凝胶用于关节软骨修复的各种精细的（生物）设计和（生物）制造方法。最后，我们总结了基于功能化水凝胶的关节软骨组织工程策略在体内外实验中所遭遇到的一些困难和挑战，同时为未来临床转化指明了方向。

关键词：关节软骨功能化水凝胶软骨修复软骨组织工程临床转化

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Progress and perspectives of neural tissue engineering

null

《医学前沿（英文）》 2015年第9卷第4期页码 401-411 doi: 10.1007/s11684-015-0415-x

摘要：

Traumatic injuries to the nervous system lead to a common clinical problem with a quite high incidence and affect the patient’s quality of life. Based on a major challenge not yet addressed by current therapeutic interventions for these diseases, a novel promising field of neural tissue engineering has emerged, grown, and attracted increasing interest. This review provides a brief summary of the recent progress in the field, especially in combination with the research experience of the author’s group. Several important aspects related to tissue engineered nerves, including the theory on their construction, translation into the clinic, improvements in fabrication technologies, and the formation of a regenerative environment, are delineated and discussed. Furthermore, potential research directions for the future development of neural tissue engineering are suggested.

关键词： nerve injury tissue engineering nerve grafts

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Bile duct injury repair — earlier is not better

null

《医学前沿（英文）》 2015年第9卷第4期页码 508-511 doi: 10.1007/s11684-015-0418-7

摘要：

Bile duct injury is a common complication of cholecystectomy. The timing of bile duct injury repair remains controversial. A recent review conducted in France reported 39% complications and 64% failure after immediate repair in 194 patients compared with 14% complications and 8% failure after late repair in 133 patients. A national review of 139 consecutive early repairs conducted at five hepatopancreaticobiliary centers in Denmark reported 4% mortality, 36% morbidity, and 42 restrictures (30%) at a median follow-up of 102 months, and only 64 patients (46%) demonstrated uneventful short-term and long-term outcomes. Most patients with bile duct injury present with bile leak and sepsis; thus, early repair is not recommended. Percutaneous drainage of bile and endoscopic stenting are the mainstays of treatment of bile leak because they convert acute bile duct injury into a controlled external biliary fistula. The ensuing benign biliary stricture should be repaired by a biliary surgeon after a delay of 4–6 weeks once the external biliary fistula has closed.

关键词： bile duct injury cholecystectomy laparoscopic cholecystectomy

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Atypical pituitary hormone–target tissue axis

《医学前沿（英文）》 2023年第17卷第1期页码 1-17 doi: 10.1007/s11684-022-0973-7

摘要： A long-held belief is that pituitary hormones bind to their cognate receptors in classical target glands to actuate their manifold functions. However, a number of studies have shown that multiple types of pituitary hormone receptors are widely expressed in non-classical target organs. Each pituitary gland-derived hormone exhibits a wide range of nonconventional biological effects in these non-classical target organs. Herein, the extra biological functions of pituitary hormones, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, adrenocorticotrophic hormone, and prolactin when they act on non-classical organs were summarized, defined by the novel concept of an “atypical pituitary hormone–target tissue axis.” This novel proposal explains the pathomechanisms of abnormal glucose and lipid metabolism, obesity, hypertension, fatty liver, and atherosclerosis while offering a more comprehensive and systematic insights into the coordinated regulation of environmental factors, genetic factors, and neuroendocrine hormones on human biological functions. The continued exploration of the physiology of the “atypical pituitary hormone–target tissue axis” could enable the identification of novel therapeutic targets for metabolic diseases.

关键词： thyroid-stimulating hormone follicle-stimulating hormone luteinizing hormone adrenocorticotrophic hormone prolactin

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The stem cell and tissue engineering research in Chinese ophthalmology

GE Jian, LIU Jingbo

《医学前沿（英文）》 2007年第1卷第1期页码 6-10 doi: 10.1007/s11684-007-0002-x

摘要： Much has been considerably developed recently in the ophthalmic research of stem cell (SC) and tissue engineering (TE). They have become closer to the clinical practice, standardized and observable. Leading edge research of SC and TE on the ocular surface reconstruction, neuroregeneration and protection, and natural animal model has become increasingly available. However, challenges remain on the way, especially on the aspects of function reconstruction and specific differentiation. This paper reviews the new developments in this area with an intention of identifying research priorities for the future.

关键词： available observable neuroregeneration protection function reconstruction

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Primary cilia in hard tissue development and diseases

《医学前沿（英文）》 2021年第15卷第5期页码 657-678 doi: 10.1007/s11684-021-0829-6

摘要： Bone and teeth are hard tissues. Hard tissue diseases have a serious effect on human survival and quality of life. Primary cilia are protrusions on the surfaces of cells. As antennas, they are distributed on the membrane surfaces of almost all mammalian cell types and participate in the development of organs and the maintenance of homeostasis. Mutations in cilium-related genes result in a variety of developmental and even lethal diseases. Patients with multiple ciliary gene mutations present overt changes in the skeletal system, suggesting that primary cilia are involved in hard tissue development and reconstruction. Furthermore, primary cilia act as sensors of external stimuli and regulate bone homeostasis. Specifically, substances are trafficked through primary cilia by intraflagellar transport, which affects key signaling pathways during hard tissue development. In this review, we summarize the roles of primary cilia in long bone development and remodeling from two perspectives: primary cilia signaling and sensory mechanisms. In addition, the cilium-related diseases of hard tissue and the manifestations of mutant cilia in the skeleton and teeth are described. We believe that all the findings will help with the intervention and treatment of related hard tissue genetic diseases.

关键词： primary cilia bone mechanical sensing hard tissue cilium-related bone disease tooth

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Expression status of GATA3 and mismatch repair proteins in upper tract urothelial carcinoma

Yue Wang, Jinxia Zhang, Yunfan Wang, Shufang Wang, Yu Zhang, Qi Miao, Fei Gao, Huiying He

《医学前沿（英文）》 2019年第13卷第6期页码 730-740 doi: 10.1007/s11684-019-0687-7

摘要： GATA binding protein 3 (GATA3) and mismatch repair (MMR) deficiency contribute to the development of urothelial carcinoma. However, the combined expression of GATA3 and microsatellite instability (MSI) in upper tract urothelial carcinoma (UTUC) and its prognostic value have not been investigated. Here, we immunohistochemically stained GATA3 and MMR proteins in 108 UTUC samples. GATA3 was positive in 74 cases, and its expression was significantly lower than in adjacent benign urothelium ( <0.001). Loss of GATA3 expression was statistically associated with adverse clinicopathologic parameters, such as advanced stage, lymphovascular invasion, neural invasion, lymph node metastasis, and extensive necrosis. Cancer-specific survival (CSS, =0.028) and disease-free survival (DFS, =0.024) were significantly shorter in patients with GATA3 negative tumors than in patients with GATA3 positive tumors. The absence of MMR proteins was observed in 8.3% of the cases, and focal staining was identified in 13.0%. When using “lax criteria” which resulted in counting cases as negative where MMR staining was in fact focally positive (<5%), we found that GATA3 was inversely associated with MSI ( =0.005). Moreover, GATA3 /microsatellite stability (MS) tumors were correlated with advanced pT stage ( <0.001) and poor outcome ( =0.019 for CSS, =0.016 for DFS) compared with GATA3 /MSI ones. The GATA3 /MSI cases had unfavorable clinical outcomes compared with GATA3 /MSI cases ( =0.008 for CSS, =0.023 for DFS). This finding raises a question as to whether GATA3 interacts with MSI through the TGF- signaling pathway and regulates UTUC progression.

关键词： upper tract urothelial carcinoma GATA binding protein 3 mismatch repair microsatellite instability prognosis

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Non-closure of the peritoneum and subcutaneous tissue at radical hysterectomy: A randomized controlled

Zhou-Fang XIONG MD, Wei-Hong DONG MD, Ze-Hua WANG MD,

《医学前沿（英文）》 2010年第4卷第1期页码 112-116 doi: 10.1007/s11684-010-0016-7

摘要： We conducted a trial to assess the influence of closure or nonclosure of the peritoneum and subcutaneous tissue on the clinical outcomes of cervical cancer patients who underwent radical hysterectomy with lower abdominal cross incision. This randomized controlled trial was performed on 158 cervical cancer patients in our hospital between January 2002 and June 2004. Eighty-two patients were allocated to the “closure” group and 76 patients to the “nonclosure” group. Results showed that non-closure of the peritoneum and subcutaneous tissue could shorten operation time and febrile duration, reduce antibiotics requirement, increase the volume of drainage and decrease the incidence of liquefaction of subcutaneous fat (<0.05). There was no difference in blood loss, postoperative complications, bowel function restoration and post-operative stay between the two groups (>0.05). Our study revealed that closure of the peritoneum and subcutaneous tissue provides no immediate postoperative benefits while unnecessarily lengthening surgical time and anesthesia exposure. The practice of closure of the peritoneum and subcutaneous tissue at radical hysterectomy should be questioned.

关键词： cervical cancer radical surgery peritoneum subcutaneous tissue