Mesenchymal stem cells and the lung

Mesenchymal stem cells (MSC) are a population of tissue‐resident adult progenitor cells that were originally identified in bone marrow, but have now been identified in many organs including the lung. Although their precise role in organ function remains incompletely defined, mounting evidence suggests that they are an important component of the parenchymal progenitor cell niche and orchestrate organ homeostasis and repair following injury. In this review, what is known about MSC biology will be outlined with particular emphasis on lung biology, and the therapeutic potential of MSC‐based cell therapy will also be highlighted.     

Mesenchymal stem cells: paradoxes of passaging

The field of stem cell biology continues to evolve with the ongoing characterization of multiple types of stem cells with their inherent potential for experimental and clinical application. Mesenchymal stem cells (MSC) are one of the most promising stem cell types due to their availability and the relatively simple requirements for in vitro expansion and genetic manipulation. Multiple populations described as "MSCs" have now been isolated from various tissues in humans and other species using a variety of culture techniques. Despite extensive in vitro characterization, relatively little has been demonstrated regarding their in vivo biology and therapeutic potential. Nevertheless, clinical trials utilizing MSCs are currently underway. The aim of this review is to critically analyze the field of MSC biology, particularly with respect to the current paradox between in vitro promise and in vivo efficacy. It is the authors' opinion that until this paradox is better understood, therapeutic applications will remain limited.     

Mesenchymal stem cells in osteoarthritis

PURPOSE OF REVIEW: Accumulating evidence indicates that every tissue contains stem cells. Our understanding of the biology of stem cells reveals that these cell populations have a critical role in the homeostasis and repair of tissues. Besides the local stem cell niches, additional compartments in the body such as the bone marrow may serve as reservoirs for stem cell populations. On more extensive tissue damage, and guided by local repair responses, "reparative" cell populations are mobilized from more distant stem cell reservoirs and migrate to the site of injury, thereby contributing in many aspects of local tissue repair. RECENT FINDINGS: Osteoarthritis has long been regarded as an imbalance between destructive and reparative processes. The lack of repair of the weight-bearing articular cartilage and the associated subchondral bone changes are considered of critical importance in the progression of the disease. Recent findings indicate a depletion and/or functional alteration of mesenchymal stem cell populations in osteoarthritis. These preliminary data suggest that in joint diseases such as osteoarthritis, it is of importance to investigate further the involvement of the stem cell pool in the mechanisms contributing to joint homeostasis and driving disease progression. SUMMARY: In view of the emerging body of evidence pointing to a potential therapeutic utility of stem cell technology, it is not surprising that local delivery of mesenchymal stem cells has been explored as a therapeutic approach in animal models of osteoarthritis.     

Mesenchymal stem cells in the infarcted heart

A loss of functional cardiomyocytes forms the cellular basis of cardiac dysfunction and heart failure. Stem cell based repletion of scarred myocardial tissue and regeneration of cardiomyocytes have been proposed as a potential treatment of ventricular dysfunction. In this review, we provide an overview of recent studies utilizing mesenchymal stem cells in cardiac regeneration and post-myocardial infarct therapy.     

Mesenchymal stem cells and the artery wall

The presence of ectopic tissue in the diseased artery wall is evidence for the presence of multipotential stem cells in the vasculature. Mesenchymal stem cells were first identified in the marrow stroma, and they differentiate along multiple lineages giving rise to cartilage, bone, fat, muscle, and vascular tissue in vitro and in vivo. Transplantation studies show that marrow-derived mesenchymal stem cells appear to enter the circulation and engraft other tissues, including the artery wall, at sites of injury. Recent evidence indicates that mesenchymal stem cells are also present in normal artery wall and microvessels and that they also may enter the circulation, contributing to the population of circulating progenitor cells and engrafting other tissues. Thus, the artery wall is not only a destination but also a source of progenitor cells that have regenerative potential. Although potential artifacts, such as fusion, need to be taken into consideration, these new developments in vascular biology open important therapeutic avenues. A greater understanding of how mesenchymal stem cells from the bone marrow or artery wall bring about vascular regeneration and repair may lead to novel cell-based treatments for cardiovascular disease.     

犬骨髓间充质干细胞可诱导分化为组织工程瓣间质种子细胞

目的诱导分化骨髓间充质干细胞（BMSC）,探讨BMSC作为组织工程瓣膜的间质种子细胞的可行性。方法分离扩增犬BMSC,定向诱导分化为成纤维细胞,以隐静脉间质细胞为对照,比较两种细胞在形态学、增殖能力、胶原合成,以及两种细胞冻存和复苏率。结果光镜下,两种细胞均为贴壁生长细胞,形态为梭形或多角型,血管间质细胞和第2代诱导BMSCs的倍增时间分别为38 h和36 h,诱导后的BMSC的冻存和复苏率、合成胶原能力与血管间质细胞之间无显著差异;电镜示两种细胞均能够种植在去细胞猪主动脉瓣上。免疫组织化学结果显示种植后瓣膜上有间质细胞生长。结论BMSC诱导后可分化为成纤维细胞与静脉来源的间质细胞无显著差别,是合适的组织工程瓣膜间质种子细胞。     

Mesenchymal stem cells and haematopoietic stem cell transplantation

The bone marrow serves as a reservoir for different classes of stem cells. In addition to haemopoietic stem cells, the bone marrow comprises a population of marrow stromal cells or mesenchymal stem cells (MSCs). These cells exhibit multilineage differentiation capacity, and are able to generate progenitors with restricted developmental potential, including fibroblasts, osteoblasts, adipocytes and chondrocyte progenitors. In addition, MSCs have been shown to possess immunosuppressive activity in vitro and in vivo. Clinical trials are underway to test whether MSCs are beneficial in patients undergoing allogeneic bone marrow transplantation. With the expanding role of stem cell transplants in different areas of medicine, including cardiology and orthopaedics, MSCs may become very important in the next few years.     

Mesenchymal stem cells for clinical application

Mesenchymal Stem Cells/Multipotent Marrow Stromal Cells (MSC) are multipotent adult stem cells present in all tissues, as part of the perivascular population. As multipotent cells, MSCs can differentiate into different tissues originating from mesoderm ranging from bone and cartilage, to cardiac muscle. Conflicting data show that MSCs could be pluripotent and able to differentiate into tissues and cells of non‐mesodermic origin as neurons or epithelial cells. Moreover, MSCs exhibit non‐HLA restricted immunosuppressive properties. This wide range of properties leads to increasing uses of MSC for immunomodulation or tissue repair. Based on their immunosuppressive properties MSC are used particularly in the treatment of graft versus host disease, For tissue repair, MSCs can work by different ways from cell replacement to paracrine effects through the release of cytokines and to regulation of immune/inflammatory responses. In regenerative medicine, trials are in progress or planed for healing/repair of different tissue or organs as bone, cartilage, vessels, myocardium, or epithelia. Although it has been demonstrated that ex‐vivo expansion processes using fetal bovine serum, recombinant growth factors (e.g. FGF2) or platelet lysate are feasible, definitive standards to produce clinical‐grade MSC are still lacking. MSCs have to be produced according GMP and regulation constraints. For answering to the numerous challenges in this fast developing field of biology and medicine, integrative networks linking together research teams, cell therapy laboratories and clinical teams are needed.     

Bone regeneration and Mesenchymal stem cells

Bone marrow mesenchymal stem cells have been considered to differentiate into cells in bone, cartilage, tendon, muscle, and fat. Further analyses revealed that these cell also give rise to myocardial cells, oval cells and nerve cells, indicating high plasticity of these cells. Recent researches have been focused to utilize these cells to regenerate not only bone but also the life-maintaining major organs. As a cell source for the future regeneration of multiple organs, regeneration of the bone marrow is critical and thus studies on the process of bone marrow regeneration will benefit not only bone physiology field alone but also that of many other organs.     

间充质干细胞与支气管哮喘

支气管哮喘是一种气道慢性炎症性疾患,同时也是一种免疫紊乱的变态反应性疾病,其发病机制复杂.间充质干细胞(mesenchymal stem cells,MSCs)是来源于中胚层的具有高度自我更新能力和多向分化潜能的多能干细胞,并且具有强大的免疫调节功能.MSCs这些独特性能将赋予它们在支气管哮喘冶疗中的潜在价值.     

Mesenchymal stem cells and autoimmune diseases

Mesenchymal stem cell (MSC) immunosuppressive properties offer a potentially attractive therapeutic modality for autoimmune diseases. MSC inhibit virtually all types of immune responses in vitro and prevent the induction of disease in several experimental models of autoimmunity. However, the processes involved in the pathogenesis of human diseases are more complicated and treatment cannot be administered before disease induction. In autoimmune diseases persistent antigenic stimulation recruits endogenous MSC to the site of lesion that contribute to the fibrotic evolution. Therefore, administering MSC to a chronic inflammatory disorder may not be desirable. In fact, MSC are not constitutively immunosuppressive but require a 'licensing' step provided by molecules of acute phase inflammation, like IFNγ and TNF-α, or toll-like receptor (TLR) ligands. Conversely, different cytokines and/or the stimulation of selective TLR make MSC to become immunostimulatory. Therefore, dissecting the inflammatory environment in autoimmune diseases will identify the best conditions amenable to successful MSC therapy.     

骨髓间充质干细胞与肺间质纤维化

间质性肺疾病（ILD）是由各种不同原因引起的一组疾病,其以肺间质纤维化为共同病理改变,是导致肺功能进行性丧失和呼吸衰竭的主要原因。特发性肺纤维化（IPF）是最常见的一种ILD,其对目前采用的药物治疗几乎无反应,预后差。目前对这类疾病发病机制的研究认为,无论是否有炎症反应,肺纤维化形成都是肺损伤与修复反复失衡的结果。间充质干细胞（MSC）是广泛存在于人体各组织中的一种成体干细胞,具有多向分化潜能。在受损肺,骨髓来源的MSC（BMd-MSC）可以分化为上皮细胞、血管内皮细胞和成纤维细胞。采用MSC疗法有可能是治疗肺纤维化最理想的方法之一。     

间充质干细胞与支气管哮喘

间充质干细胞是一种具有多向分化潜能的成体干细胞,拥有强大的免疫调节能力。它可减轻支气管哮喘（简称哮喘）的气道炎症,有利于哮喘的治疗,又可参与哮喘的气道重塑,加重哮喘病理改变,具有双面性。若能深入探讨、明确其在哮喘中的作用机制,趋利避害,可望给哮喘的治疗开辟更广阔的前景。     

Mesenchymal stem cells in allergic diseases: Current status

Allergic diseases, which include asthma, allergic skin diseases, allergic rhinitis and allergic conjunctivitis, have already garnered worldwide public health attention over recent decades. Mesenchymal stem cells (MSCs) have gradually emerged as a potential method for treating allergic diseases due to their immunosuppressive characteristics, tissue repair ability and secretion of various biological factors. This potential of MSC-based therapy has been confirmed in clinical and preclinical studies, which report the therapeutic benefits of MSCs for various allergic diseases and explore the antiallergic mechanisms. In this review, we focus on the discoveries and biological mechanisms of MSCs as a therapeutic tool in allergic diseases. We discuss the challenges of conducting MSC studies as well as future directions.