智能化水凝胶在原位心肌组织工程的应用

原位心肌组织工程在近年取得了突飞猛进的发展,它是指利用生物材料携带细胞移植于心肌梗死及其周边部位防治心肌梗死后心力衰竭,为细胞治疗提供了基质,提高了细胞的存活率,现就生物材料可注射水凝胶在原位心肌组织工程的应用作一综述.     

生物材料在心脏再生修复过程中的应用

心肌梗死是冠状动脉急性、持续性缺血缺氧所引起的心肌坏死,发病率和死亡率居高不下。虽然通过冠状动脉介入或溶栓药物等治疗手段恢复血供,能提高患者的生存率,但难以挽救梗死区丢失的心肌细胞,而成年哺乳动物心脏自身修复能力有限是造成心肌纤维化,最终进展为心力衰竭的主要因素。长期以来,已有的治疗手段难以逆转心肌梗死后的心力衰竭进程。细胞移植有望成为促进梗死修复与再生最有前景的治疗方法,由于缺血缺氧微环境导致移植后有限的干细胞存活和保留,结果不是很理想。而脱细胞生物材料以促进血管生成和减轻纤维化显示了临床前治疗潜力。该综述概述了各种脱细胞生物材料及通过微创的方式进行心外膜修复及心肌内注射促进心脏再生、改善心脏功能的利与弊,为将来利用脱细胞生物材料结合优化的药物促进心肌再生提供参考。     

水凝胶在心肌组织工程中的研究进展

近年来用于心肌组织工程研究的生物材料不断被广大学者研究和重视起来,水凝胶以其一定的韧性、流变性、良好的生物相容性和可降解性被越来越广泛地应用于心肌组织工程。水凝胶在心室重构、改善心功能等方面都发挥着重要作用。本文以水凝胶在心肌组织工程中的研究进展做一综述。     

生物材料治疗心肌梗死疾病的应用进展

心肌梗死是严重危及人类健康的致死性及致残性疾病,尽管药物、介入及外科手术策略的进展极大降低了心肌梗死患者的病死率,但很难从根本上使已经坏死或纤维化的心肌恢复正常.心脏组织工程为冠心病的治疗开创了新思路,适当的生物材料不但可以为梗死后受损的心肌细胞提供基质支撑,还具有促进损伤组织自身修复的内在可能.现综述生物材料对于心肌梗死疾病的治疗应用.     

纤维蛋白凝胶在心肌梗死治疗中的应用进展

采用组织工程技术和生物材料对心肌梗死后受损的心肌进行修复是近年来研究的热点。纤维蛋白凝胶作为一种支架材料在组织工程领域得到广泛地应用。它既承担了输送细胞和蛋白质等的载体作用,又起到了提供细胞外基质的作用,促进了细胞的增殖与分化。现主要从纤维蛋白凝胶的结构特性及在治疗心肌梗死中的应用做一综述。     

影像学评估心肌存活性的研究进展

近年来存活心肌无创成像在血运重建治疗中的作用是国内外研究的热点。临床上存活心肌是指细胞结构完整、代谢功能正常的心肌细胞,心肌的存活性表现为心肌具有收缩储备和心肌组织灌注完整两个方面。“罪犯”血管供血区存在一定量的存活心肌是再血管化治疗改善心肌供血、缓解心衰症状、提高患者生存质量的前提,因此识别和尽量挽救可逆性缺血心肌是临床工作的重点。本篇综述主要基于早期检测和评价的存活心肌的重要性与必要性,就存活心肌的定义及意义、评估方法、有关存活心肌在再血管化治疗中作用的多中心前瞻性研究进行综述,以提高对存活心肌在再血管化治疗中作用的认识和临床应用。     

生物材料在干细胞移植治疗心肌梗死中的应用

<正>生物材料是一类具有特殊功能的、用于机体组织修复和再生的材料。目前,生物材料在干细胞培养和移植方面受到广泛关注。生物材料既可作为干细胞的支架,也可以作为移植干细胞临时的黏附基质。一种理想的生物材料应当模拟细胞外基质,它必须能够维持细胞的生长,并有利于细胞的存活和分化,在新生组织形成过程中逐渐降解。对生物材料进行生物活性组分的修饰,可以调控干细胞的生物学特征以及改善移植部位的局部微环境,从而增强移植干细胞的存活和分化,有利于组织功能的改善。目前,多种生物材料已用于心肌梗死的治疗,现针对生物材料在干细胞移植治疗心肌梗死中的作用及其机制的研究新进展作一综述。 1 用于心肌梗死治疗的生物材料 1.1 天然材料天然材料主要是指哺乳动物细胞外基质的各种成分,如胶原蛋白、纤维蛋白原、Matrigel、明胶等。天然材料还包括从植物或动物提取的一些成分,如壳聚糖、纤维素和丝纤蛋     

干细胞治疗对心肌修复的研究

在心血管疾病的治疗中,各种心脏疾病后心肌组织的再生修复仍是当前面临的一个严峻挑战。心肌细胞的各种自然修复过程在临床上并不能挽救受损的心肌,而干细胞治疗作为一种外源性促进心肌修复的方法,使当前的治疗从补救心肌向组织再生转变。该文从自体干细胞和异体干细胞移植两个方面,将目前应用干细胞修复受损心肌的主要策略及现况作一综述。     

干细胞治疗对心肌修复的研究

在心血管疾病的治疗中,各种心脏疾病后心肌组织的再生修复仍是当前面临的一个严峻挑战。心肌细胞的各种自然修复过程在临床上并不能挽救受损的心肌,而干细胞治疗作为一种外源性促进心肌修复的方法,使当前的治疗从补救心肌向组织再生转变。该文从自体干细胞和异体干细胞移植两个方面,将目前应用干细胞修复受损心肌的主要策略及现况作一综述。     

克山病人心肌组织中辅酶Q含量的研究

本文在克山病人心肌组织辅酶 Q_(10)的定量测定中,首次发现克山病人心肌组织辅酶Q_(10)含量较正常人为低,使克山病患者心肌能量代谢发生障碍的发病机理得到进一步的证实。为克山病的临床治疗和心肌能量代谢的研究提供了启示。     

Biomaterials for the treatment of myocardial infarction

For nearly a decade, researchers have investigated the possibility of cell transplantation for cardiac repair. More recently, the emerging fields of tissue engineering and biomaterials have begun to provide potential treatments. Tissue engineering approaches are designed to repair lost or damaged tissue through the use of growth factors, cellular transplantation, and biomaterial scaffolds. There are currently 3 biomaterial approaches for the treatment of myocardial infarction (MI). The first involves polymeric left ventricular restraints in the prevention of heart failure. The second utilizes in vitro engineered cardiac tissue, which is subsequently implanted in vivo. The final approach entails injecting cells and/or a scaffold into the myocardium to create in situ engineered cardiac tissue. This review gives an overview of the current progress in the growing field of biomaterials for the treatment of MI.     

Biomaterials for the treatment of myocardial infarction.

For nearly a decade, researchers have investigated the possibility of cell transplantation for cardiac repair. More recently, the emerging fields of tissue engineering and biomaterials have begun to provide potential treatments. Tissue engineering approaches are designed to repair lost or damaged tissue through the use of growth factors, cellular transplantation, and biomaterial scaffolds. There are currently 3 biomaterial approaches for the treatment of myocardial infarction (MI). The first involves polymeric left ventricular restraints in the prevention of heart failure. The second utilizes in vitro engineered cardiac tissue, which is subsequently implanted in vivo. The final approach entails injecting cells and/or a scaffold into the myocardium to create in situ engineered cardiac tissue. This review gives an overview of the current progress in the growing field of biomaterials for the treatment of MI.     

Autologous cell transplantation for the treatment of damaged myocardium

Autologous cell transplantation for the treatment of damaged myocardium after myocardial infarction is becoming an increasingly promising strategy. This form of treatment can be divided into 2 treatment strategies: The first uses differentiated cell types to replace the scarred tissue with living cells, while the second strategy uses stem cells in an attempt to regenerate myocardium. Over the past decade, multiple cell types have been used in animal studies, and clinical trials to determine the safety of injecting and engrafting skeletal myoblasts into damaged myocardium are presently being conducted. Animals studies focused on using stem cells to regenerate damaged myocardium have shown a naturally occurring reparative process that consists of up-regulation of progenitor cell release from the bone marrow after myocardial infarction, homing of these cells to the injured tissue, and differentiation of these progenitor cells into vascular cells and cardiac myocytes within the infarcted tissue. Unfortunately, this process occurs with great infrequency. Strategies to regenerate myocardium with stem cells either extract stem cells from the bone marrow and inject these cells into the damaged area or they attempt to increase the efficiency of the natural reparative process by increasing the mobilization of bone marrow-derived stem cells after myocardial infarction. This review summarizes the field of cell transplantation over the past decade, discusses areas of controversy, and proposes an outline of advancements that need to be made in both the clinical and scientific arenas for autologous cell transplantation to fully reach its clinical potential.     

Cardiac tissue engineering: a clinical perspective

Engineered myocardium may be used to repair myocardial defects. Although not clinically applicable yet, initial studies in rodents have demonstrated the feasibility of tissue engineering based myocardial repair in vivo. In order for restorative treatment to evolve into a functional treatment modality, tissue engineers have to generate human myocardium of sufficient size and with relevant contractile function to replace/repair myocardial defects. This requires the identification of a scalable and ideally autologous cardiomyocyte source as well as the development of strategies to overcome size limitations. We will further address pivotal issues pertaining to the allocation of suitable human cells for myocardial tissue engineering and discuss the translation of present myocardial tissue engineering concepts into preclinical, as well as clinical, trials.     

Stem Cell-Based Cardiac Tissue Engineering

Cardiovascular diseases are the leading cause of death worldwide, and cell-based therapies represent a potential cure for patients with cardiac diseases such as myocardial infarction, heart failure, and congenital heart diseases. Towards this goal, cardiac tissue engineering is now being investigated as an approach to support cell-based therapies and enhance their efficacy. This review focuses on the latest research in cardiac tissue engineering based on the use of embryonic, induced pluripotent, or adult stem cells. We describe different strategies such as direct injection of cells and/or biomaterials as well as direct replacement therapies with tissue mimics. In this regard, the latest research has shown promising results demonstrating the improvement of cardiac function with different strategies. It is clear from recent studies that the most important consideration to be addressed by new therapeutic strategies is long-term functional improvement. For this goal to be realized, novel and efficient methods of cell delivery are required that enable high cell retention, followed by electrical integration and mechanical coupling of the injected cells or the engineered tissue to the host myocardium.     

Strategies for Tissue Engineering Cardiac Constructs to Affect Functional Repair Following Myocardial Infarction

Tissue-engineered cardiac constructs are a high potential therapy for treating myocardial infarction. These therapies have the ability to regenerate or recreate functional myocardium following the infarction, restoring some of the lost function of the heart and thereby preventing congestive heart failure. Three key factors to consider when developing engineered myocardial tissue include the cell source, the choice of scaffold, and the use of biomimetic culture conditions. This review details the various biomaterials and scaffold types that have been used to generate engineered myocardial tissues as well as a number of different methods used for the fabrication and culture of these constructs. Specific bioreactor design considerations for creating myocardial tissue equivalents in vitro, such as oxygen and nutrient delivery as well as physical stimulation, are also discussed. Lastly, a brief overview of some of the in vivo studies that have been conducted to date and their assessment of the functional benefit in repairing the injured heart with engineered myocardial tissue is provided.     

Reprogramming cells for transplantation

The field of tissue engineering, involving the reprogramming of stem cells or rejuvenation of specific differentiated cells, is emerging as a promising strategy to repair the damaged myocardium. The eventual goal is to be able to take a patient's own cells, expand them ex vivo, genetically engineer them to enhance specific properties, and then reintroduce them into the patient's heart to create a replacement tissue. Our review paper describes data that supports the potential of this strategy. This clinically relevant, combined strategy of genetic and tissue engineering could be of importance in treating elderly patients with massive myocardial damage, patients whose normal myogenic or angiogenic cells have been depleted or are inadequate in their growth potential, to prevent LV deterioration and heart failure.     

Targeting of Lin-Sca+ hematopoietic stem cells with bispecific antibodies to injured myocardium

Bispecific antibodies (BiAbs) are being used to target T cells or other immune cells to antigen-specific tumor targets. Anti-CD3 activated T cells (ATC) armed with anti-CD3 x anti-HER2 BiAb (HER2Bi) have been used to target Her2/neu + breast and prostate carcinoma cells. We adapted BiAb technology to target stem cells to injured myocardium. Since myocardial infarctions can lead to cardiac death and disability, rapid repair and rejuvenation of damaged myocardium is critically needed. Effective homing of stem cells and transdifferentiation of the stem cells into functional elements of the myocardium is needed for repair of damaged myocardium. We use a BiAb that binds c-kit on murine stem cells and VCAM-1 adhesion molecules up-regulated on injured myocardial cells. To test for specific binding and homing in a mouse, we produced anti-c-kit x anti-VCAM-1 to target purified Lin-Sca+ murine stem cells to the injured myocardium. Mice with infarcts created by ligation of the left anterior descending artery (LAD) were directly injected with armed stem cells or injected via the internal jugular vein (IJ) with FACS sorted Lin-Sca+ stem cells from bone marrow after fluorescent dye labeling. There were increased numbers of armed Lin-Sca+ cells retained in infracted myocardium after direct injection of armed Lin-Sca+ cells and increased numbers of Lin-Sca+ cells that were found in injured myocardium after IJ injection. These results suggest that stem cells retargeted with BiAb can be directly injected and retained by injured myocardium or targeted to injured myocardial tissues for tissue regeneration.     

Autologous stem cells for functional myocardial repair

Recent experimental studies based on innovative hypothesis utilizing cell therapy for the damaged myocardium are recently becoming increasingly promising. The naturally occurring myocardial reparative process is apparently complex and relatively inefficient. It consists of up-regulation of progenitor cell release from the bone marrow after myocardial infarction, homing of these cells to the injured tissue, and differentiation of these progenitor cells into vascular cells and cardiomyocytes within the infarcted tissue. Accordingly, there are two main strategies to regenerate myocardium with autologous stem cells: (1) Extracting stem cells from the bone marrow and injecting these cells into the damaged area, (2) Increasing the efficiency of the naturally occurring reparative process by increasing the mobilization of bone marrow–derived stem cells after myocardial infarction.This review summarizes the growing field of autologous stem cell utilization over the past decade and outlines scientific and clinical hurdles that need to be overcome before this therapy can fully reach its clinical potential.