特异性骨靶向纳米递药系统的优势与临床可应用性

文题释义： 药物靶向性：靶向药物是在目标器官或组织局部形成相对高的浓药物度,减少对非目标器官、组织、细胞的伤害。目前根据靶向目标不同,可分为组织器官水平、细胞水平及亚细胞水平几个层次。根据靶向机制的不同,药物靶向可分为被动靶向、主动靶向、物理靶向等几类,其中的主动靶向即特异性靶向。 纳米药物递送系统：药物递送系统是利用临床医学、药学及材料科学等多学科手段,在恰当的时机将适量的药物递送到正确的位置,从而增加药物的利用效率,提高疗效,降低成本,减少毒副作用。纳米级药物递送系统是指在药剂学中把纳米载体负载治疗药物形成粒径1-1 000 nm纳米粒。因为其纳米级粒径可以使得药物在体内穿过某些生物屏障如血-脑屏障、血-骨髓屏障等,以及利用肿瘤组织的高渗透长滞留效应而达到被动靶向的效果,但其缺乏特异性。背景：在骨相关疾病治疗中特异性主动靶向递药系统非常重要,而纳米技术的发展为其提供了良好的平台,同时为其提供了新的研究思路。 目的：针对以特异性骨靶向递药系统的目前发展及未来前景做一综述。 方法：应用计算机在PubMed、Web of Science和Medline等数据库检索涉及主动骨靶向性递药系统与纳米级递药系统的相关研究,检索关键词为“Bone target therapy,Nanoparticles,Drug delivery system”,检索时间为2014年3月至2019年3月。 结果与结论：靶向基团是特异性骨靶向递药系统的重要组成部分,它决定了递药系统的靶向效率。到目前为止已发现针对于骨组织、破骨细胞、成骨细胞、骨髓间充质干细胞的靶向分子,它们有各自优缺点。目前特异性骨靶向纳米递药系统已在各种骨病领域得到了广泛研究,如转移骨质疏松症、骨髓炎、多发性骨髓瘤、骨肉瘤、骨转移癌等。纳米载体应用的优势为其带来了临床潜力的同时也存在许多挑战,尽管许多基础研究显示出很好的体内结果,但很少有骨靶向基团修饰的纳米递药系统成功地将其转化为临床。 ORCID: 0000-0001-8512-0447(向海滨) 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

本期提示

干细胞是一类具有自我复制能力的多潜能细胞,在一定条件下,它可以分化成多种功能细胞。近年来,干细胞研究和临床应用越来越受到重视,各国均不遗余力地投入大量的科研经费对干细胞进行研究、干细胞作为一种具有再生各种组织器官潜能的组织细胞,在器官移植、细胞治疗、组织工程、生殖医学等多个领域的临床应用前景广泛,目前在多个热点研究领域取得了令人瞩目的成就,干细胞研究已经成为二十一世纪国际生命科学研究中最具有发展潜力的方向之一。     

脂肪源性干细胞基质胶的研究进展

脂肪源性干细胞基质胶(SVF-gel)是利用物理方法从脂肪组织中提取的一种可注射凝胶状生物材料,其包含高浓度的脂肪干细胞(ADSC)及细胞外基质,具有独特的再生模式,局部移植也展现出了良好的干细胞治疗潜力。文章从目前中国国内的研究现状出发,就SVF-gel的生物学特性、参与组织修复再生的作用机制和临床应用现状进行综述,并对未来应用前景提出展望,以期为SVF-gel在组织修复领域的应用提供新的思路。     

神经系统疾病的干细胞治疗☆

背景：干细胞具有自我更新和多向分化的生物学特性,在生理或病理情况下能维持组织器官内环境的稳定,近年被广泛用于再生医学的研究。 目的：对神经系统疾病的干细胞治疗进展进行综述。 方法：通过Pubmed数据库检索有关干细胞治疗神经系统疾病的相关文献。检索词为“stem cells、Nervous system diseases、therapy”。初检得到298篇文献,最终保留54篇符合标准的文献进行分析。 结果与结论：经过近些年的研究,干细胞被认为是神经损伤和变性疾病的一个很有前景的治疗手段。通过干细胞的移植,取代受损的神经细胞,促进受损神经网络的恢复从而重建神经功能。     

组织工程材料在修复心肌损伤中的应用研究进展

心肌梗死(MI)严重危及人类的健康,在治疗心血管疾病研究领域中,心肌组织缺乏自我修复能力是当前面临的挑战之一。现有的临床治疗手段无法恢复MI后病灶的心脏功能。心肌组织工程是修复受损心肌组织的重要潜在途径,组织工程材料可用于干细胞(骨髓间充质干细胞、胚胎干细胞等)、生长因子(VEGF、IL-7等)的递送以及模拟细胞外基质。该领域的主要研究包括支架材料、干细胞及生长因子等递送修复心肌,目前已取得显著进展。对近年来心肌组织工程材料作为递送载体修复受损心肌的不同应用形式进行综述,主要包括心脏补片、可注射水凝胶、三维多孔支架、心脏芯片和聚合物微胶囊等热点研究内容,并对组织工程材料的发展进行展望。     

间充质干细胞作为新型纳米靶向抗肿瘤药物载体的研究进展

近年来,作为药剂学研究热点领域之一的靶向给药系统受到越来越多的关注.然而,这些抗肿瘤靶向载药运输系统存在诸多缺点如靶向效率低等而限制其在临床上的应用,提高肿瘤靶向效率已成为纳米药物研发和临床应用的瓶颈问题.因此,迫切需要设计并开发新型靶向药物递送载体.最近研究表明,间充质干细胞(MSCs)具有肿瘤趋向性和可迁移等特点,这些特点使得它们能够作为理想的抗肿瘤靶向药物递送载体来治疗实体瘤和转移瘤.综述了利用间充质干细胞作为肿瘤治疗的靶向药物递送载体的研究进展,概述了该系统存在的问题和挑战,并提出了针对这些问题的解决方法.     

间充质干细胞来源外泌体与再生医学：无细胞疗法临床应用的未来

文题释义：外泌体：是一种区别于微泡,具有特异脂质、蛋白、信使RNA和微小非编码RNA的微小膜性囊泡结构,其大小均一,直径为40-100 nm,密度为1.10-1.18 g/mL,可通过细胞内吞泡膜向内凹陷形成多泡内涵体并与细胞膜融合后而释放。外泌体内主要含有核酸、蛋白质和脂质等,并可在清除废弃物质、介导细胞间信息传递、产生免疫耐受、肿瘤治疗疫苗及组织修复再生等方面发挥作用。 再生医学：是指使功能无法自行恢复的病变组织、器官通过临床治疗措施得到结构和功能的重建,其研究的主要内容是干细胞如何发育成组织并应用干细胞潜能进行组织替代疗法,旨在改善受损、功能障碍和缺失的组织及器官的再生。间充质干细胞是目前再生医学研究中广泛使用的细胞类型,而其发挥作用在很大程度上是由其旁分泌主导而实现的。 背景：外泌体是一种微小的膜性囊泡结构,是间充质干细胞旁分泌的重要组成部分,可将信息传递至损伤的细胞或组织从而参与组织再生。 目的：将外泌体及其在再生医学中的研究进展进行综述。 方法：在PubMed、CNKI数据库中进行相关文献检索,以“exosomes,mesenchymal stem cells,tissue regeneration and repair”及“外泌体,间充质干细胞,组织再生修复”为关键词进行检索,通过阅读文题和摘要进行初步筛选,排除与文章主题不相关的文献,最终纳入63篇文献进行结果分析。 结果与结论：外泌体内含多种成分,其提取方法多样,具有清除废弃物质、介导细胞间信息传递、产生免疫耐受及作为肿瘤治疗疫苗等众多功能。间充质干细胞来源外泌体在组织再生与修复中发挥重要作用,具有较好的应用前景,但若要作为无细胞疗法投入临床使用,还需更多深入研究和探索。 ORCID: 0000-0002-9862-334X(杨琨) 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

脐带间充质干细胞在骨科疾病中的应用

再生医学的发展在多种疑难疾病的修复治疗中业已显示一定的作用。自体组织被认为是再生医学临床应用的优选生物医学材料,人UC-MSCs可能是非常理想的细胞来源,具有临床治疗软骨、骨软骨损伤和骨缺损的潜力。UC-MSCs移植对于骨骼疾病,骨关节炎、骨质疏松及股骨头坏死等的治疗,多是针对发病机制进行的有效治疗,可增强血管化和骨再生,在临床中已取得一定的效果。这种新型的干细胞在颅颌面和骨科组织工程的应用前景广泛,但依然存在许多问题与不足需要进一步研究。     

干细胞库研究应用进展

<正>干细胞是一类具有自我复制更新和多向分化潜能的原始细胞群体,在一定条件下,它可以分化成多种功能的细胞或组织器官。干细胞可用于白血病、心血管疾病、糖尿病、骨及软骨缺损、老年性痴呆、帕金森病、自身免疫性疾病、脊髓损伤和遗传性缺陷以及恶性肿瘤等疾病的治疗。同时,干细胞也是目前组织工程最理想的种子细胞,具有再生其他组织器官的能力,干细胞可用作组织工程和细胞工程的种子     

细胞外基质性生长因子递送系统如何促进骨再生

文题释义：细胞外基质：细胞外基质是器官和组织以及细胞附着、分化、增殖和迁移的独特支持结构，其可调控细胞的多种行为。同时，细胞外基质还是生长因子的储存库，其多种成分可结合并调控生长因子的活性。 生长因子递送系统：是指在时空和剂量上可对生长因子在生物体内分布进行全面调控的技术体系，其目标是在合适的时机将适量的生长因子递送到所需要的位置，增加生长因子的生物利用度，提高疗效和降低成本的同时并减少不良反应。   摘要背景：生长因子的局部应用为难愈性骨缺损治疗提供了很有前景的治疗策略，但其仍存在诸多限制因素，如无法精确控制生长因子的释放量及生长因子释放后生物活性较低等，因此生长因子递送系统的改良是亟待解决的问题。 目的：总结多种包含细胞外基质成分的生长因子递送系统及其在骨缺损治疗方面的最新研究进展。 方法：由第一作者以“extracellular matrix，integrins，heparin，growth factor，controlled delivery system，bone defect，细胞外基质，整合蛋白，肝素，生长因子，缓释系统，骨缺损”为关键词，检索2007至2019年期间PubMed、Web of Science、Medline、万方、CNKI数据库中的相关文献。初检文章317篇，筛选后对59篇文章进行分析。结果与结论：细胞外基质成分可结合并调控生长因子的活性，提高其生物利用度。因此将细胞外基质成分整合入生长因子递送系统中可达到对生长因子递送系统的改良。与普通生长因子递送系统相比，细胞外基质性生长因子递送系统可以获得更好的生长因子结合效果，更高的生物活性与利用度，甚至更好的靶向性释放，产生更好的促进骨再生的治疗效果。因此细胞外基质性生长因子递送系统为难愈性骨缺损局部治疗提供了更优良的治疗策略。 ORCID: 0000-0002-7643-2278(石军) 中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程     

Concise review: Adipose-derived stem cells as a novel tool for future regenerative medicine

The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift that may provide alternative therapeutic solutions for a number of diseases. The use of either embryonic stem cells (ESCs) or induced pluripotent stem cells in clinical situations is limited due to cell regulations and to technical and ethical considerations involved in the genetic manipulation of human ESCs, even though these cells are, theoretically, highly beneficial. Mesenchymal stem cells seem to be an ideal population of stem cells for practical regenerative medicine, because they are not subjected to the same restrictions. In particular, large number of adipose-derived stem cells (ASCs) can be easily harvested from adipose tissue. Furthermore, recent basic research and preclinical studies have revealed that the use of ASCs in regenerative medicine is not limited to mesodermal tissue but extends to both ectodermal and endodermal tissues and organs, although ASCs originate from mesodermal lineages. Based on this background knowledge, the primary purpose of this concise review is to summarize and describe the underlying biology of ASCs and their proliferation and differentiation capacities, together with current preclinical and clinical data from a variety of medical fields regarding the use of ASCs in regenerative medicine. In addition, future directions for ASCs in terms of cell-based therapies and regenerative medicine are discussed.     

Recent Progress on Tissue-Resident Adult Stem Cell Biology and Their Therapeutic Implications

Recent progress in the field of the stem cell research has given new hopes to treat and even cure diverse degenerative disorders and incurable diseases in human. Particularly, the identification of a rare population of adult stem cells in the most tissues/organs in human has emerged as an attractive source of multipotent stem/progenitor cells for cell replacement-based therapies and tissue engineering in regenerative medicine. The tissue-resident adult stem/progenitor cells offer the possibility to stimulate their in vivo differentiation or to use their ex vivo expanded progenies for cell replacement-based therapies with multiple applications in human. Among the human diseases that could be treated by the stem cell-based therapies, there are hematopoietic and immune disorders, multiple degenerative disorders, such as Parkinson's and Alzheimer's diseases, type 1 or 2 diabetes mellitus as well as eye, liver, lung, skin and cardiovascular disorders and aggressive and metastatic cancers. In addition, the genetically-modified adult stem/progenitor cells could also be used as delivery system for expressing the therapeutic molecules in specific damaged areas of different tissues. Recent advances in cancer stem/progenitor cell research also offer the possibility to targeting these undifferentiated and malignant cells that provide critical functions in cancer initiation and progression and disease relapse for treating the patients diagnosed with the advanced and metastatic cancers which remain incurable in the clinics with the current therapies.     

Tissue engineering and cell-based therapy toward integrated strategy with artificial organs

Research in order that artificial organs can supplement or completely replace the functions of impaired or damaged tissues and internal organs has been underway for many years. The recent clinical development of implantable left ventricular assist devices has revolutionized the treatment of patients with heart failure. The emerging field of regenerative medicine, which uses human cells and tissues to regenerate internal organs, is now advancing from basic and clinical research to clinical application. In this review, we focus on the novel biomaterials, i.e., fusion protein, and approaches such as three-dimensional and whole-organ tissue engineering. We also compare induced pluripotent stem cells, directly reprogrammed cardiomyocytes, and somatic stem cells for cell source of future cell-based therapy. Integrated strategy of artificial organ and tissue engineering/regenerative medicine should give rise to a new era of medical treatment to organ failure.     

Sources of Stem Cells for Regenerative Medicine

The shortage of organ donors for regenerative medicine has stimulated research on stem cells as a potential resource for cell-based therapy. Stem cells have been used widely for regenerative medicine applications. The development of innovative methods to generate stem cells from different sources suggests that there may be new alternatives for cell-based therapies. Here, we provide an overview of human embryonic stem cells (hES) and the methods for obtaining these cells and other broadly multipotent or pluripotent cell types. These methods include somatic cell nuclear transfer, single cell embryo biopsy, arrested embryos, altered nuclear transfer, and reprogramming somatic cells. We also discuss the use of amniotic-fluid derived stem cells (AFS) for potential patient-specific therapies.     

Cellular MRI and its role in stem cell therapy

Hematopoietic, stromal and organ-specific stem cells are under evaluation for therapeutic efficacy in cell-based therapies of cardiac, neurological and other disorders. It is critically important to track the location of directly transplanted or infused cells that can serve as gene carrier/delivery vehicles for the treatment of disease processes and be able to noninvasively monitor the temporal and spatial homing of these cells to target tissues. Moreover, it is also necessary to determine their engraftment efficiency and functional capability following transplantation. There are various in vivo imaging modalities used to track the movement and incorporation of administered cells. Tagging stem cells with different contrast agents can make these cells probes for different imaging modalities. Recent reports have shown that stem cells labeled with iron oxides can be used as cellular MRI probes demonstrating the cell trafficking to target tissues. In this review, we will discuss the status and future prospect of stem cell tracking by cellular MRI for cell-based therapy.     

Current Understanding of the Pathways Involved in Adult Stem and Progenitor Cell Migration for Tissue Homeostasis and Repair

With the advancements in the field of adult stem and progenitor cells grows the recognition that the motility of primitive cells is a pivotal aspect of their functionality. There is accumulating evidence that the recruitment of tissue-resident and circulating cells is critical for organ homeostasis and effective injury responses, whereas the pathobiology of degenerative diseases, neoplasm and aging, might be rooted in the altered ability of immature cells to migrate. Furthermore, understanding the biological machinery determining the translocation patterns of tissue progenitors is of great relevance for the emerging methodologies for cell-based therapies and regenerative medicine. The present article provides an overview of studies addressing the physiological significance and diverse modes of stem and progenitor cell trafficking in adult mammalian organs, discusses the major microenvironmental cues regulating cell migration, and describes the implementation of live imaging approaches for the exploration of stem cell movement in tissues and the factors dictating the motility of endogenous and transplanted cells with regenerative potential.     

Adipose Derived Stem Cells and Smooth Muscle Cells: Implications for Regenerative Medicine

The treatment of chronic wounds and other damaged tissues and organs remains a difficult task, in spite of greater adherence to recognised standards of care and a better understanding of pathophysiologic principles. Adipose derived stem cells (ADSCs), with their proliferative and impressive differentiation potential, may be used in the future in autologous cell therapy or grafting to replace damaged tissues. At this point in time, transplanted tissues are often rejected by the body. Autologous grafting would eliminate this problem. ADSCs are able to differentiate into a number of cells in vitro, for example smooth muscle cells (SMCs), when treated with lineage specific factors. SMCs play a key role in physiology and pathology as they form the principle layer of all SMC tissues. Smooth muscle biopsies are often impractical and morbid, and often lead to a low cell harvest. It has also been shown that SMCs derived from a diseased organ can lead to abnormal cells. Therefore, there is a great need for alternative sources of healthy SMCs. The use of ADSCs for cell-based tissue engineering (TE) represents a promising alternative for smooth muscle repair. This review discusses the potential uses of ADSCs and SMCs in regenerative medicine, and the potential of ADSCs to be differentiated into functional SMCs for TE and regenerative cellular therapies to repair diseased organs.     

Stem cell-delivery therapeutics for periodontal tissue regeneration

Periodontitis, an inflammatory disease, is the most common cause of tooth loss in adults. Attempts to regenerate the complex system of tooth-supporting apparatus (i.e., the periodontal ligament, alveolar bone and root cementum) after loss/damage due to periodontitis have made some progress recently and provide a useful experimental model for the evaluation of future regenerative therapies. Concentrated efforts have now moved from the use of guided tissue/bone regeneration technology, a variety of growth factors and various bone grafts/substitutes toward the design and practice of endogenous regenerative technology by recruitment of host cells (cell homing) or stem cell-based therapeutics by transplantation of outside cells to enhance periodontal tissue regeneration and its biomechanical integration. This shift is driven by the general inability of conventional therapies to deliver satisfactory outcomes, particularly in cases where the disease has caused large tissue defects in the periodontium. Cell homing and cell transplantation are both scientifically meritorious approaches that show promise to completely and reliably reconstitute all tissue and connections damaged through periodontal disease, and hence research into both directions should continue. In view of periodontal regeneration by paradigms that unlock the body's innate regenerative potential has been reviewed elsewhere, this paper specifically explores and analyses the stem cell types and cell delivery strategies that have been or have the potential to be used as therapeutics in periodontal regenerative medicine, with particular emphasis placed on the efficacy and safety concerns of current stem cell-based periodontal therapies that may eventually enter into the clinic.     

Muscle stem cells in development, regeneration, and disease

Somatic stem cell populations participate in the development and regeneration of their host tissues. Skeletal muscle is capable of complete regeneration due to stem cells that reside in skeletal muscle and nonmuscle stem cell populations. However, in severe myopathic diseases such as Duchenne Muscular Dystrophy, this regenerative capacity is exhausted. In the present review, studies will be examined that focus on the origin, gene expression, and coordinated regulation of stem cell populations to highlight the regenerative capacity of skeletal muscle and emphasize the challenges for this field. Intense interest has focused on cell-based therapies for chronic, debilitating myopathic diseases. Future studies that enhance our understanding of stem cell biology and repair mechanisms will provide a platform for therapeutic applications directed toward these chronic, life-threatening diseases.     

Cell delivery in cardiac regenerative therapy

There is a growing interest in the clinical application of stem cells as a novel therapeutic approach for treatment of myocardial infarction and prevention of subsequent heart failure. Transplanted stem cells improve cardiac functions through multiple mechanisms, which include but are not limited to promoting angiogenesis, replacing dead cardiomyocytes, modulating cardiac remodeling. Most of the results obtained so far are exciting and very promising, spawning an increasing number of clinical trials recently. However, many problems still remain to be resolved such as the best delivery method for transplantation of cells to the injured myocardium and the issue of how to optimize the delivery of targeted cells is of exceptional clinical relevance. In this review, we focus on the different delivery strategies in cardiac regenerative therapy, as well as provide a brief overview of current clinical trials utilizing cell-based therapy in patients with ischemic heart disease.