Mesenchymal stem cells

The tremendous capacity of bone to regenerate is indicative of the presence of stem cells with the capability, by definition, to self-renew as well as to give rise to daughter cells. These primitive progenitors, termed mesenchymal stem cells or bone marrow stromal stem cells, exist postnatally, and are multipotent with the ability to generate cartilage, bone, muscle, tendon, ligament, and fat. Given the demographic challenge of an ageing population, the development of strategies to exploit the potential of stem cells to augment bone formation to replace or restore the function of traumatized, diseased, or degenerated bone is a major clinical and socioeconomic need. Owing to the developmental plasticity of mesenchymal stem cells, there is great interest in their application to replace damaged tissues. Combined with modern advances in gene therapy and tissue engineering, they have the potential to improve the quality of life for many. Critical in the development of this field will be an understanding of the phenotype, plasticity, and potentiality of these cells and the tempering of patients' expectations driven by commercial and media hype to match current laboratory and clinical observations.     

Mesenchymal stem cells cannot affect mRNA expression of toll-like receptors in different tissues during sepsis

Objective and design

Experimental animal models and human clinical studies support a crucial role for TLRs in infectious diseases. The aim of this study was to test the ability of MSCs, which have immunomodulatory effects, of altering the mRNA expression of toll-like receptors during a experimental model of sepsis in different tissues.

Materials and methods

Three experimental groups (male C57BL/6 mice) were formed for the test: control group, untreated septic group and septic group treated with MSCs (1 × 10⁶ cells/animal). Lungs, cortex, kidney, liver and colon tissue were dissected after 12 h of sepsis induction and TLR2/3/4/9 mRNA were evaluated by RT-qPCR.

Results

We observed a decrease of TLR2 and 9 mRNA expression in the liver of the sepsis group, while TLR3 was decreased in the lung and liver. No change was found between the sepsis group and the sepsis + MSC group.

Conclusions

In this model of experimental sepsis the MSCs were unable to modify the mRNA expression of the different toll-like receptors evaluated.

     

Mesenchymal stem cells in tissue engineering

The repair of diseased or damaged cartilage remains one of the most challenging problems of musculoskeletal medicine. Tissue engineering advances in cartilage repair have utilized autologous and allogenic chondrocyte and cartilage grafts, biomaterial scaffolds, growth factors, stem cells, and genetic engineering. The mesenchymal stem cell has specifically attracted much attention because of its accessibility, potential for differentiation, and manipulability to modern molecular, tissue and genetic engineering techniques. Mesenchymal stem cells provide invaluable tools for the study of tissue repair when combined with a carrier vehicle/matrix scaffold, and/or bioactive growth factors. However, an underappreciated source of knowledge lies in the relationship between fetal development and adult tissue repair. The multitude of events that take place during fetal development which lead from stem cell to functional tissue are poorly understood. A more thorough understanding of the events of development as they pertain to cartilage organogenesis may help elucidate some of the unknowns of adult tissue repair.     

Mesenchymal stem cells in autoimmune disease

Autoimmune diseases afflict more than 3% of the U.S. population. Current therapy for mild to moderate cases is symptomatic, however advanced cases suffer high morbidity and mortality. Advanced patients have benefited from stem cell therapy in the form of bone marrow transplantation in conjunction with high-dose cytotoxic therapy. Broader application of stem cell therapy requires better understanding of how adult stem cells affect development and foster treatment of autoimmune pathologies, and of better ways to manipulate the host immune responses. While extensive research documents the role of hematopoietic stem cells (HSCs) in autoimmune disease, few studies have addressed if and how mesenchymal stem cells (MSCs) contribute to their etiopathology. Recent characterization of MSCs and their role in hematopoiesis and immune modulation suggest that their potential for cell therapy extends beyond their traditional accessory function in HSC engraftment. MSCs contribute significantly to tissue restructuring and immune functioning, in addition to facilitating durable, long-lasting stem cell engraftment. MSCs are relatively easy to obtain and expand in in vitro cultures, rendering them a prime candidate for genetic manipulations for stem cell therapy. They have the potential to differentiate into multiple lineages such as osteoblasts, adipose tissue, cartilage, tendon, and stromal cells. The role of MSCs for autoimmune disease therapy could thus be based both on immune function modulation and contribution to hematopoiesis. In this review, we examine the biology of MSCs, and their potential for cell therapy of autoimmune disease.     

间充质干细胞在炎症免疫调节中的作用及应用进展

背景：研究表明,间充质干细胞的主要功能有直接参与损伤修复,分泌生长因子,调节免疫和炎症,抗氧化应激等,可用于治疗多种急、慢性疾病。 目的：综述间充质干细胞在炎症免疫调节中的研究进展。 方法：以“干细胞,间充质干细胞,免疫调节,炎症,免疫细胞,炎症因子,治疗”为中文检索词,以“stem cells,mesenchymal stem cells,immune regulation,inflammation,immune cells,inflammatory factors,treatment”为英文检索词,在万方、中国知网期刊全文数据库和PubMed数据库检索2005年1月至2015年8月有关干细胞参与炎症免疫调节的文献。排除陈旧性和重复性研究,最终纳入40篇文献进行综述。 结果与结论：间充质干细胞因其具有免疫调节及多向分化的特性,越来越受到临床的重视,同时间充质干细胞易于从不同组织中获取并且具有良好的体外扩增能力,使得其在组织损伤炎症与修复的临床运用中具有广阔的前景。作为最有希望进入临床应用阶段的种子细胞,间充质干细胞在许多疾病的治疗中表现出了它的优越性,特别是对于免疫调节失衡导致的炎症性相关疾病的治疗中表现出良好的效果。相信在未来的细胞生物治疗领域,间充质干细胞将占有重要的地位。 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     

Mesenchymal stem cells for vascular regeneration

Mesenchymal stem cells (MSCs) have tremendous potential for regenerative medicine, and have been researched for the treatment of cardiovascular diseases. MSCs are a promising cell type because of their ease of isolation and expansion, their multipotency and their low immunogenicity. However, in order to fully utilize the therapeutic potential of MSCs, it is important to understand the intrinsic property of MSCs and the role of the microenvironment in modulating MSC behavior and function. Microenvironmental factors such as mechanical cues, soluble factors and matrix properties not only regulate MSC differentiation, but also modulate MSC signaling to the surrounding environment. Understanding the properties of MSCs and the role of the microenvironment will be beneficial for developing in vivo therapies for the construction of tissue-engineered vascular grafts and the treatment of ischemic cardiac tissues.     

间充质干细胞与血液系统疾病

近年来间充质干细胞一直是细胞生物学研究领域的热点之一,其自我更新、多向分化能力以及强的免疫调节功能等生物学特性已被广泛认识,有关它在相关疾病治疗中应用的基础与临床研究也取得了一定进展。随着研究的深入,间充质干细胞在一些疾病的发生、发展过程中所起的作用也逐渐被认识。本文就间充质干细胞与一些血液系统疾病之间的关系进行综述。     

Mesenchymal stem cells for cartilage engineering

Injuries to articular cartilage are one of the most challenging issues of musculoskeletal medicine due to the poor intrinsic ability of this tissue for repair. Despite progress in orthopaedic surgery, cell-based surgical therapies such as autologous chondrocyte transplantation (ACT) have been in clinical use for cartilage repair for over a decade but this approach has shown mixed results. Moreover, the lack of efficient modalities of treatment for large chondral defects has prompted research on tissue engineering combining chondrogenic cells, scaffold materials and environmental factors.This paper focuses on the main parameters in tissue engineering and on the potential of mesenchymal stem cells (MSCs) as an alternative to cells derived from patient tissues in autologous transplantation and tissue engineering. Here we discuss the prospects of using autologous chondrocytes or MSCs in regenerative medicine and summarize the advantages and disadvantages of these cells in articular cartilage engineering.     

Mesenchymal stem cells and adipogenesis in hemangioma involution

Hemangioma is a benign tumor of infancy whose hallmark is rapid growth during the first year of life followed by slow regression during early childhood. The proliferating phase is characterized by abundant immature endothelial cells, the involuting phase by prominent endothelial-lined vascular channels and endothelial apoptosis, and the involuted phase by few remaining capillary-like vessels surrounded by loose fibrofatty tissue. Nothing is known about the mechanisms that contribute to the adipogenesis during this spontaneous regression. We postulated that mesenchymal stem cells (MSCs) reside in the tumor and preferentially differentiate into adipocytes. To test this hypothesis, we isolated MSCs from 14 proliferating and five involuting hemangiomas by taking advantage of the well known selective adhesion of MSCs to bacteriologic dishes. These hemangioma-derived MSCs (Hem-MSCs) are similar to MSCs obtained from human bone marrow, expressing the cell surface markers SH2 (CD105), SH3, SH4, CD90, CD29, smooth muscle alpha-actin, and CD133 but not the hematopoietic markers CD45 and CD14 or the hematopoietic/endothelial markers CD34, CD31, and kinase insert domain receptor (KDR). Hem-MSCs exhibited multilineage differentiation with robust adipogenic potential that correlated with the proliferating phase. The numbers of adipogenic Hem-MSCs were higher in proliferating-phase than in involuting-phase tumors and higher than in normal infantile skin. Furthermore, Hem-MSCs exhibited a random pattern of X-chromosomal inactivation, indicating that these cells are not clonally derived. In summary, we have identified MSCs as a novel cellular constituent in infantile hemangioma. These MSCs may contribute to the adipogenesis during hemangioma involution.     

Mesenchymal stem cells stimulate antibody secretion in human B cells

Mesenchymal stem cells (MSC) have immunomodulatory effects and inhibit T-cell responses to alloantigens and mitogens in vitro and in vivo. We wanted to examine the effect of MSC on human B cells. MSC stimulated IgG production, measured in an enzyme-linked immunospot (ELIspot) assay in blood and spleen lymphocytes. MSC only induced a low proliferation. When a semipermeable membrane separated MSC and mononuclear cells, the IgG production was stimulated in unfractionated lymphocytes. In contrast, enriched B cells required cell contact with MSC to produce IgG. Co-cultures of MSC and lymphocytes increased IFN-gamma production. MSC produce IL-6, and addition of MSC to spleen cells dramatically increased IL-6 levels. After lymphocyte stimulation with lipopolysaccharide (LPS), cytomegalovirus or varicella zoster virus, MSC either stimulated or inhibited IgG response, depending on the level of stimulation by LPS or the viral antigens. Similar results were obtained for enriched B cells. To conclude, MSC stimulate B-cell antibody secretion. The IgG secretion by activated B cells may be stimulated or inhibited by the addition of MSC, depending on the level of stimulation.     

Mesenchymal stem cells: isolation and therapeutics

Mesenchymal stem cells (MSCs) are progenitors of all connective tissue cells. In adults of multiple vertebrate species, MSCs have been isolated from bone marrow (BM) and other tissues, expanded in culture, and differentiated into several tissue-forming cells such as bone, cartilage, fat, muscle, tendon, liver, kidney, heart, and even brain cells. Recent advances in the practical end of application of MSCs toward regeneration of a human-shaped articular condyle of the synovial joint is one example of their functionality and versatility. The present review not only outlines several approaches relevant to the isolation and therapeutic use of MSCs, but also presents several examples of phenotypic and functional characterization of isolated MSCs and their progeny.     

Mesenchymal stem cells in the aging and osteoporotic population

Because of their ability to self-renew and differentiate, mesenchymal stem cells (MSCs) are the in vivo source for replacing lost cells in high-turnover tissues during the life of an organism. MSCs have osteogenic potential and can be eligible for the repair and maintenance of the skeleton, thus they are very attractive for tissue engineering and regenerative medicine approaches. However, many changes in their behavior, caused by aging and bone disease, have been reported in the literature. These changes, which affect MSC self-renewal ability and differentiation potentiality, are related to cell proliferation, differentiation, cell cycle phases (depending on gene modification), and cytokine and growth factor production. This review summarizes the literature related to intrinsic and extrinsic characteristics of human bone marrow or adipose tissue MSCs during aging and osteoporosis. Although some studies reveal contrasting results, the results of this review suggest that the cellular modifications due to aging and osteoporosis should be carefully considered in relation to the use of MSCs for therapeutic application.     

Mesenchymal stem cells can be differentiated into endothelial cells in vitro

Human bone marrow-derived mesenchymal stem cells (MSCs) have the potential to differentiate into mesenchymal tissues like osteocytes, chondrocytes, and adipocytes in vivo and in vitro. The aim of this study was to investigate the in vitro differentiation of MSCs into cells of the endothelial lineage. MSCs were generated out of mononuclear bone marrow cells from healthy donors separated by density gradient centrifugation. Cells were characterized by flow cytometry using a panel of monoclonal antibodies and were tested for their potential to differentiate along different mesenchymal lineages. Isolated MSCs were positive for the markers CD105, CD73, CD166, CD90, and CD44 and negative for typical hematopoietic and endothelial markers. They were able to differentiate into adipocytes and osteocytes after cultivation in respective media. Differentiation into endothelial-like cells was induced by cultivation of confluent cells in the presence of 2% fetal calf serum and 50 ng/ml vascular endothelial growth factor. Laser scanning cytometry analysis of the confluent cells in situ showed a strong increase of expression of endothelial-specific markers like KDR and FLT-1, and immunofluorescence analysis showed typical expression of the von Willebrand factor. The functional behavior of the differentiated cells was tested with an in vitro angiogenesis test kit where cells formed characteristic capillary-like structures. We could show the differentiation of expanded adult human MSCs into cells with phenotypic and functional features of endothelial cells. These predifferentiated cells provide new options for engineering of artificial tissues based on autologous MSCs and vascularized engineered tissues.     

间充质干细胞治疗类风湿性关节炎的研究与应用

背景：目前的研究发现来源于骨髓或脂肪组织的间充质干细胞具有免疫抑制及抗炎的特性,使得其在治疗类风湿性关节炎等自身免疫性疾病方面具有广阔的应用前景。 目的：综述间充质干细胞的生物学特性、特别是免疫抑制及抗炎作用机制及其在治疗类风湿性关节炎方面的研究进展。 方法：检索2005/2011西文生物医学期刊文献数据及CNKI 数据库有关类风湿性关节炎研究、骨髓间充质干细胞生物学特性及其免疫抑制作用、在类风湿性关节炎方面的应用方面的文献,英文检索词为“marrow stem cells,rheumatoid arthritis,immunosuppressive”,中文检索词为“间充质干细胞,类风湿性关节炎,免疫抑制”,纳入近年来起重大影响以及开启和引领新方向的重要研究成果,排除重复性研究,纳入24篇文章进行综述。 结果与结论：间充质干细胞在维持关节组织的内环境稳态,如调控炎症反应及免疫应答、抗纤维化及组织再生方面具有重要的作用,而间充质干细胞在治疗类风湿性关节炎方面疗效的稳定性及安全性方面仍需进一步的研究。