关节液来源间充质干细胞在组织工程中应用研究进展

间充质干细胞是治疗软骨损伤的新方法,间充质干细胞的来源选择是目前研究重点。关节液来源间充质干细胞(SF-MSC)是从关节液中分离而来,具有间充质干细胞的生物学特性。SF-MSC易于获取,与脂肪和骨髓来源的间充质干细胞相比,其具有更强的软骨分化能力,被认为是治疗软骨损伤的理想种子细胞。体内研究证实,SF-MSC复合支架材料或关节内注射SF-MSC对修复软骨损伤有很好的效果。目前研究表明,SF-MSC有望成为治疗软骨损伤的候选间充质干细胞。该文就SF-MSC在组织工程中应用的研究进展作一综述。     

膝关节牵伸术修复膝关节软骨的研究进展

膝关节牵伸术是近年来治疗膝骨关节炎的新技术,它能减轻膝关节疼痛和改善膝关节功能,这与其修复软骨的作用密不可分。膝关节牵伸术修复软骨的作用机制和影响因素作为当前研究的热点,本文通过回顾文献发现,膝关节牵伸术能减轻膝关节负荷为软骨修复提供适宜的力学环境,引起的膝关节流体静水压波动不仅能帮助软骨吸收营养,还能促进软骨形成基因和抑制软骨基质降解酶基因表达。此外,膝关节牵伸术为滑液间充质干细胞募集到软骨损伤处创造了条件,并提升了滑液间充质干细胞增殖、分化为成软骨谱系的能力。膝关节牵伸术还能通过减少膝关节内部炎性因子含量和抑制炎性基因表达,减轻膝关节炎症反应和软骨损伤。目前已知的影响膝关节牵伸术修复软骨的因素包括适当增加膝关节负重活动、牵伸高度和牵伸时间有助于软骨修复,男性患者、膝关节炎严重程度更高的患者膝关节牵伸术后软骨修复效果更好。而膝关节牵伸术后第1年软骨修复疗效越好,预示着膝关节牵伸术保留膝关节的远期生存率越高。但目前对上述热点的研究只停留在初期阶段,仍需进行更深入的探索,才能对膝关节牵伸术的临床应用起到更好的指导。     

间充质干细胞在软骨组织工程中的应用

间充质干细胞具有高度自我更新能力,能够分化为各种类型的细胞.近20年间充质细胞在软骨组织工程中得到应用,动物实验显示了良好的软骨修复潜能,成为软骨组织工程的理想的细胞来源.组织工程和干细胞技术已经确定为对软骨缺损有效的治疗方法,间充质干细胞有望在软骨组织工程中得到更广泛的应用.本文对间充质干细胞的特性和在组织工程中的应用进行了综述.     

脂肪来源干细胞在医美修复重建领域的研究及应用进展

随着骨髓间充质干细胞在临床中的广泛应用，其存在的缺陷严重影响了修复效果。脂肪来源干细胞(ADSCs)是由间充质细胞分化而来，与骨髓间充质干细胞相似，且能够有效地弥补其在临床治疗中的缺陷，因此获得了人们的广泛关注。脂肪来源干细胞在医美修复重建领域具有重要意义。本文旨在分析脂肪来源干细胞在医美修复重建领域的研究及应用效果。     

髌下脂肪垫来源间充质干细胞软骨分化的研究进展

间充质干细胞(MSCs)为重点的组织工程学研究已成为软骨损伤修复与再生的研究热点,髌下脂肪垫(IPFP)是脂肪间充质干细胞(ASCs)的新型优良组织来源,其取材方便,供区损伤小。且IPFP-ASCs体外增殖快,成软骨分化能力较强。低氧,转化生长因子β1、β3,骨形态发生蛋白7等可以促进其分化。体内试验表明其可以有效改善软骨损伤患者症状,提高关节功能。虽然目前仍存在生物学和技术上的困难需克服,但IPFP-ASCs有望成为修复包括骨关节炎在内的关节软骨损伤的良好策略。     

脂肪间充质干细胞治疗膝关节骨关节炎应用进展

膝关节骨关节炎(KOA)的特征是关节透明软骨局灶性丧失,滑膜组织炎症伴骨赘形成.目前KOA的治疗方法虽可在一定程度上减轻患者疼痛并改善关节活动度,但不能促进受损关节的软骨再生.脂肪间充质干细胞作为种子细胞,可用于KOA治疗中修复受损的关节软骨,为KOA治疗提供了一种新思路.该文对脂肪间充质干细胞治疗KOA的研究进展进行...     

不同来源的间充质干细胞治疗骨与软骨组织疾病的研究进展

近年来,随着细胞和组织工程技术的发展,间充质干细胞广泛受到关注和研究,具有易分离获取、培养过程相对简单等优点,并且能够自我更新并分化成多种细胞类型,包括成骨细胞、软骨细胞、脂肪细胞等,是较为理想的种子细胞。在骨髓间充质干细胞大量的研究基础上,脂肪、骨骼肌、滑膜等多种不同来源的间充质干细胞也广泛应用在骨及软骨组织的体内研究和体外研究中。虽然间充质干细胞在基础性研究方面取得了飞跃进展,但在临床推广应用干细胞治疗上还面临着诸多问题,如对间充质干细胞的分化机理尚不明确,对其定向分化无法进行精确调控,且存在诸多限制骨和软骨再生的几个因素,很大程度上影响治疗的效果,故仍需进一步深入研究。     

滑膜间充质干细胞在软骨修复组织工程中的研究进展

关节软骨一旦损伤将很难修复，运用自体软骨细胞移植治疗软骨损伤，愈后较好，但由于细胞来源不足以及供体部位病变等缺点，使其运用受到了限制，因此运用间充质干细胞（mesenchymalstemcells，MSCs）来修复软骨损伤具有很好的应用前景。     

间充质干细胞成软骨分化相关研究进展

软骨细胞移植疗法已成功应用于软骨损伤修复和软骨组织工程研究,但软骨细胞取材有限,因此探索软骨细胞替代物成为研究热点。间充质干细胞具有分化为骨、软骨等组织的潜能,在软骨损伤、骨关节炎修复及软骨组织工程等方面起着重要作用。该文就间充质干细胞成软骨分化相关研究进展作一综述。     

间充质干细胞及其来源的外泌体在骨关节炎治疗中的研究进展

骨关节炎（OA）是最常见的慢性退行性骨关节疾病，由于软骨的自愈能力有限，目前的治疗策略对OA无法达到治愈效果。近年来，越来越多的证据表明间充质干细胞治疗OA可获得较好的疗效。深入研究表明，间充质干细胞的旁分泌机制可在机体异常条件下发挥抗炎、免疫调节作用，而外泌体可能在此机制中扮演着重要的角色。外泌体可通过调控细胞间信号转导、损伤组织修复及免疫调节等过程，从而延缓OA进程。间充质干细胞及其来源的外泌体为治疗OA提供了新的治疗策略，但仍需更大量及大型动物研究以更好的验证间充质干细胞及其来源的外泌体用于治疗OA的生物安全性和治疗特征。本文就间充质干细胞及其来源的外泌体在OA中的作用及机制作一综述。     

Cell transplantation for articular cartilage defects: principles of past, present, and future practice

As articular cartilage has very limited self-repair capability, the repair and regeneration of damaged cartilage is a major challenge. This review aims to outline the past, present, and future of cell therapies for articular cartilage defect repair. Autologous chondrocyte implantation (ACI) has been used clinically for more than 20 years, and the short, medium, and long-term clinical outcomes of three generation of ACI are extensively overviewed. Also, strategies of clinical outcome evaluation, ACI limitations, and the comparison of ACI clinical outcomes with those of other surgical techniques are discussed. Moreover, mesenchymal stem cells and pluripotent stem cells for cartilage regeneration in vitro, in vivo, and in a few clinical studies are reviewed. This review not only comprehensively analyzes the ACI clinical data but also considers the findings from state-of-the-art stem cell research on cartilage repair from bench and bedside. The conclusion provides clues for the future development of strategies for cartilage regeneration.     

Restoration of Injured or Degenerated Articular Cartilage

Intra-articular fractures, ligamentous and meniscal injuries, and articular cartilage breakdown are major causes of degenerative joint disease. Lesions on the articular surface seem to have a limited capacity for repair and often progress inexorably toward osteoarthritis. Recent studies on joint immobilization and cartilage atrophy, however, have shown that repair and remodeling of articular cartilage may be possible. Currently used clinical methods of stimulating cartilage repair and remodeling include alteration of the loading on degenerated joints (primarily by using osteotomies), introduction of new cartilage-forming cells by perforation of subchondral bone, and soft-tissue arthroplasty. These procedures provide temporary relief in selected patients, but they often do not predictably restore long-term joint function. Experimentally, cartilage repair has been stimulated successfully with the use of allografts of periosteum and perichondrium, which serve as sources of cells with chondrogenic potential; introduction of cells grown in culture (stem cells or chondrocytes); stimulation by fibrin clot formation; artificial collagen matrices combined with cell transplants; and chondrogenic growth factors. The long-term success of all these methods has not been explored thoroughly, even in animal studies. Nevertheless, some research results are sufficiently encouraging to suggest that repair of the degenerating articular cartilage may be possible in the future.     

磁力靶向传递SPIO标记的BMSC修复关节软骨缺损的研究进展

关节软骨缺损修复一直是国内外研究的热点与难点。骨髓间充质干细胞移植技术具有良好的应用前景,但干细胞靶向问题亟待解决。该文阐述干细胞靶向传递的新策略--磁力靶向传递技术,重点介绍该技术应用于修复关节软骨缺损的背景、优势及存在的技术难点,并对该技术的应用前景进行展望。     

Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees

OBJECTIVE: There is no widely accepted method to repair articular cartilage defects. Bone marrow mesenchymal cells have the potential to differentiate into bone, cartilage, fat and muscle. Bone marrow mesenchymal cell transplantation is easy to use clinically because cells can be easily obtained and can be multiplied without losing their capacity of differentiation. The objective of this study was to apply these cell transplantations to repair human articular cartilage defects in osteoarthritic knee joints. DESIGN: Twenty-four knees of 24 patients with knee osteoarthritis (OA) who underwent a high tibial osteotomy comprised the study group. Adherent cells in bone marrow aspirates were culture expanded, embedded in collagen gel, transplanted into the articular cartilage defect in the medial femoral condyle and covered with autologous periosteum at the time of 12 high tibial osteotomies. The other 12 subjects served as cell-free controls. RESULTS: In the cell-transplanted group, as early as 6.3 weeks after transplantation the defects were covered with white to pink soft tissue, in which metachromasia was partially observed. Forty-two weeks after transplantation, the defects were covered with white soft tissue, in which metachromasia was observed in almost all areas of the sampled tissue and hyaline cartilage-like tissue was partially observed. Although the clinical improvement was not significantly different, the arthroscopic and histological grading score was better in the cell-transplanted group than in the cell-free control group. CONCLUSIONS: This procedure highlights the availability of autologous culture expanded bone marrow mesenchymal cell transplantation for the repair of articular cartilage defects in humans.     

Age-related biological characterization of mesenchymal progenitor cells in human articular cartilage

Adult articular cartilage has a low regeneration capacity due to lack of viable progenitor cells caused by limited blood supply to cartilage. However, recent studies have demonstrated the existence of chondroprogenitor cells in articular cartilage. A critical question is whether these mesenchymal progenitor cells are functionally viable for tissue renewal and cartilage repair to postpone cartilage degeneration. This study was designed to compare the number and function of mesenchymal progenitor cells in articular cartilage collected from human fetuses, healthy adults (aged 28-45 years), and elderly adults (aged 60-75 years) and cultured in vitro. We detected multipotent mesenchymal progenitor cells, defined as CD105+/CD166+ cells, in human articular cartilage of all ages. However, mesenchymal progenitor cells accounted for 94.69%±2.31%, 4.85%±2.62%, and 6.33%±3.05% of cells in articular cartilage obtained from fetuses, adults, and elderly patients, respectively (P<.001). Furthermore, fetal mesenchymal progenitor cells had the highest rates of proliferation measured by cell doubling times and chondrogenic differentiation as compared to those from adult and elderly patients. In contrast, alkaline phosphatase levels, which are indicative of osteogenic differentiation, did not show significant reduction with aging. However, spontaneous osteogenic differentiation was detected only in mesenchymal progenitor cells from elderly patients (with lower Markin scales). The lower chondrogenic and spontaneous osteogenic differentiation of mesenchymal progenitor cells derived from elderly patients may be associated with the development of primary osteoarthritis. These results suggest that measuring cartilage mesenchymal progenitor cells may not only identify underlying mechanisms but also offer new diagnostic and therapeutic potential for patients with osteoarthritis.     

In vivo evaluation of stem cell aggregates on osteochondral regeneration

To date, many osteochondral regenerative approaches have utilized varied combinations of biocompatible materials and cells to engineer cartilage. Even in cell‐based approaches, to date, no study has utilized stem cell aggregates alone for regenerating articular cartilage. Thus, the purpose of this study was to evaluate the performance of a novel stem cell‐based aggregate approach in a fibrin carrier to regenerate osteochondral defects in the Sprague‐Dawley rat trochlear groove model. Two different densities of rat bone marrow mesenchymal stem cell (rBMSC) aggregates were fabricated by the hanging drop technique. At 8 weeks, the cell aggregates supported the defects and served as a catalyst for neo‐cartilage synthesis, and the experimental groups may have been beneficial for bone and cartilage regeneration compared to the fibrin‐only control and sham groups, as evidenced by histological assessment. The cell density of rBMSC aggregates may thus directly impact chondrogenesis. The usage of cell aggregates with fibrin as a cell‐based technology is a promising and translational new treatment strategy for repair of cartilage defects. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1606–1616, 2017.

     

New perspectives for articular cartilage repair treatment through tissue engineering: A contemporary review

In this paper review we describe benefits and disadvantages of the established methods of cartilage regeneration that seem to have a better long-term effectiveness. We illustrated the anatomical aspect of the knee joint cartilage, the current state of cartilage tissue engineering, through mesenchymal stem cells and biomaterials, and in conclusion we provide a short overview on the rehabilitation after articular cartilage repair procedures. Adult articular cartilage has low capacity to repair itself, and thus even minor injuries may lead to progressive damage and osteoarthritic joint degeneration, resulting in significant pain and disability. Numerous efforts have been made to develop tissue-engineered grafts or patches to repair focal chondral and osteochondral defects, and to date several researchers aim to implement clinical application of cell-based therapies for cartilage repair. A literature review was conducted on PubMed, Scopus and Google Scholar using appropriate keywords, examining the current literature on the well-known tissue engineering methods for the treatment of knee osteoarthritis.