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Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE) caused by uncontrolled activation of the complement system. Mesenchymal stem cells (MSCs) exhibit clinical efficacy for severe LN in our previous studies, but the underlying mechanisms of MSCs regulating complement activation remain largely unknown. Here we show that significantly elevated C5a and C5b-9 were found in patients with LN, which were notably correlated with proteinuria and different renal pathological indexes of LN. MSCs suppressed systemic and intrarenal activation of C5, increased the plasma levels of factor H (FH), and ameliorated renal disease in lupus mice. Importantly, MSCs transplantation up-regulated the decreased FH in patients with LN. Mechanistically, interferon-α enhanced the secretion of FH by MSCs. These data demonstrate that MSCs inhibit the activation of pathogenic C5 via up-regulation of FH, which improves our understanding of the immunomodulatory mechanisms of MSCs in the treatment of lupus nephritis., Graphical Abstract Unlabelled Image, Highlights • Extensively activated C5 might contribute to the progression of lupus nephritis. • MSCs ameliorated renal disease in lupus mice through inhibiting systemic and intrarenal activation of C5. • MSCs increased plasma FH in lupus mice and patients, while interferon-α enhanced the secretion of FH from MSCs. Lupus nephritis (LN) is one of the most common manifestations of systemic lupus erythematosus (SLE). Here we show that obviously increased C5a and C5b-9 were found in patients with LN, and which were notably correlated with some clinical parameters of LN. Mesenchymal stem cells (MSCs) reduced renal disease in lupus mice through factor H (FH), one of complement regulatory proteins, suppressing C5 over-activation. Interestingly, enhanced secretion of FH from MSCs could be induced by interferon-α. The findings would expand our understanding of the complement regulatory mechanisms of MSCs in treating lupus nephritis.

Summary Allogeneic mesenchymal stem/stromal cells (MSCs) have been widely studied as an alternative cell source for regenerative medicine. Here, we report a long-term follow-up study of allogeneic bone marrow and/or umbilical cord MSC transplantation (MSCT) in severe and drug-refractory systemic lupus erythematosus (SLE) patients. Eighty-one patients were enrolled, and the 5-year overall survival rate was 84% (68/81) after MSCT. At 5-year follow-up, 27% of patients (22/81) were in complete clinical remission and another 7% (6/81) were in partial clinical remission, with a 5-year disease remission rate of 34% (28/81). In total, 37 patients had achieved clinical remission and then 9 patients subsequently relapsed, with 5-year overall rate of relapse of 24% (9/37). SLE Disease Activity Index scores, serum albumin, complement C3, peripheral white blood cell, and platelet numbers, as well as proteinuria levels, continued to improve during the follow-up. Our results demonstrated that allogeneic MSCT is safe and resulted in long-term clinical remission in SLE patients., Highlights • Mesenchymal stem/stromal cell therapy shows a 5-year survival rate of 84% for lupus • 34% of refractory lupus patients are in clinical remission after cell therapy • Mesenchymal stem/stromal cell treatment ameliorates multi-organ function in lupus, In this article, Sun and colleagues show that allogeneic bone marrow and/or umbilical cord-derived mesenchymal stem/stromal cell transplantation both result in good clinical safety and effect in treating drug-refractory systemic lupus erythematosus patients, by introducing a 5- to 8-year follow-up study for all the 81 enrolled patients.

The identification of putative multi-potential dental stem cell populations, capable of regenerating organized tooth structures, has stimulated interest into the potential use of postnatal stem cell-based therapies to treat the damage caused by trauma, cancer, and caries. Dental pulp tissue is obtained principally from impacted third molars or exfoliated deciduous teeth which are then subjected to enzymatic digestion to generate single cell suspensions. A minor proportion of dental pulp cells demonstrate the capacity to form clonogenic clusters of cells, where the progeny of some of these colonies exhibit similar characteristics attributed to bone marrow-derived mesenchymal stem cells. Xenogeneic transplant studies, assessing the developmental potential of dental pulp-derived stem/progenitors cells, have shown that these cells have the capacity to generate a vascularized dentin-pulp-like tissue in vivo, with distinct odontoblast layers lining the mineralized dentin matrix. Furthermore, ex vivo expanded dental-derived stem/progenitors cells express a heterogeneous assortment of markers associated with mesenchymal stem cells, dentin, bone, smooth muscle, neural tissue, and endothelium. This chapter describes the current evidence that multipotential mesenchymal stem cell-like populations are associated with postnatal dental pulp tissues, and speculates on the future clinical benefits that may arise from these studies.

Tissue engineering is an interdisciplinary field of biomedical research, which combines life, engineering, and materials sciences, to progress the maintenance, repair, and replacement of diseased and damaged tissues. This ever-emerging area of research applies an understanding of normal tissue physiology to develop novel biomaterial and cell-based technologies for clinical and non-clinical applications. As evident in numerous medical disciplines, tissue engineering strategies are now being increasingly developed and evaluated as potential treatments of pathological conditions in dental sciences, particularly periodontology, endodontics, oral and craniofacial surgery, dental implantology, orthodontics and dentofacial orthopedics, organ bioengineering, and transplant medicine. To further understand the concept of oral and craniofacial applications covered in the textbook, this introductory chapter will discuss the emergence of tissue engineering technology and our current understanding of the discipline, the challenges and recent developments within the field, particularly in stem cell-based therapy, and the prospective future application of translational tissue engineering products as routine therapies for tissue repair and regeneration.

Stem Cell Biology and Tissue Engineering in Dental Sciences bridges the gap left by many tissue engineering and stem cell biology titles to highlight the significance of translational research in this field in the medical sciences. It compiles basic developmental biology with keen focus on cell and matrix biology, stem cells with relevance to tissue engineering biomaterials including nanotechnology and current applications in various disciplines of dental sciences; viz., periodontology, endodontics, oral & craniofacial surgery, dental implantology, orthodontics & dentofacial orthopedics, organ engineering and transplant medicine. In addition, it covers research ethics, laws and industrial pitfalls that are of particular importance for the future production of tissue constructs. Tissue Engineering is an interdisciplinary field of biomedical research, which combines life, engineering and materials sciences, to progress the maintenance, repair and replacement of diseased and damaged tissues. This ever-emerging area of research applies an understanding of normal tissue physiology to develop novel biomaterial, acellular and cell-based technologies for clinical and non-clinical applications. As evident in numerous medical disciplines, tissue engineering strategies are now being increasingly developed and evaluated as potential routine therapies for oral and craniofacial tissue repair and regeneration. . Diligently covers all the aspects related to stem cell biology and tissue engineering in dental sciences: basic science, research, clinical application and commercialization. . Provides detailed descriptions of new, modern technologies, fabrication techniques employed in the fields of stem cells, biomaterials and tissue engineering research including details of latest advances in nanotechnology. . Includes a description of stem cell biology with details focused on oral and craniofacial stem cells and their potential research application throughout medicine. . Print book is available and black and white, and the ebook is in full color

Periodontitis leading to the progressive destruction of tooth-supporting tissues (including periodontal ligament, alveolar bone and cementum) is the major cause of tooth loss in adults. Currently available therapies for periodontal morbidities are clearly inadequate, with significant limitations in the predictable regeneration of the multiple lost/damaged periodontal tissues and the reconstruction of their complex structures. Recent scientific advances, however, have facilitated the identification of a wide variety of stem cells that may serve as novel ‘tools’ for cellular replenishment and tissue regeneration. Meanwhile, great progress has been made in developing biomaterials to support transplanted cells and to act as templates for the growth of new tissue. Furthermore, these biomaterials are routinely being designed to display and deliver regulatory signals in a precise and near-physiological fashion, which may orchestrate wound healing and regeneration. The concept of tissue engineering has been integrated into research and applications which attempt to regenerate the damaged periodontium by selective combination of stem cells, growth factors and such materials systems. This chapter provides an overview of the components involved in the established and proposed periodontal bioengineering strategies. Certain fundamental issues and design endeavors in relation to the cell-free and cell-based approaches that are being actively pursued to address specific demands are evaluated and illustrated. Future development highlights the importance of translational research to create a clinically feasible treatment regimen that may improve health care for patients.

Postnatal stem cells have been isolated from a variety of tissues. These stem cells are thought to possess great therapeutic potential for repairing damaged and/or defective tissues. Clinically, hematopoietic stem cells have been successfully used for decades in the treatment of various diseases and disorders. However, the therapeutic potential of other postnatal stem cell populations has yet to be realized, because of the lack of detailed understanding of their stem cell characteristics at the cellular and molecular levels. Furthermore, there is limited knowledge of their therapeutic value at the preclinical level. Therefore, it is necessary to develop optimal strategies and approaches to overcome the substantial challenges currently faced by researchers examining the clinical efficacy of different postnatal stem cell populations. In this review, we introduce methodologies for isolating postnatal stem cells from human dental pulp and discuss their potential role in tissue regeneration.

Postnatal stem cells have been isolated from a variety of tissues and they are highly expected to have potentiality to be utilized for cell-based clinical therapies. Bone marrow stromal stem cells (BMSSCs) derived from bone marrow stromal tissue have been identified as a population of multipotent mesenchymal stem cells that are capable of differentiating into osteoblasts, adipocytes, chondrocytes, muscle cells, and neural cells. The most significant tissue regeneration trait of BMSSCs is their in vivo bone regeneration capability, which has been widely studied for understanding molecular and cellular mechanisms of osteogenesis, and, more importantly, developing into a stem-cell-based therapy. Recent studies further demonstrated that BMSSC-mediated bone regeneration is a promising approach for regenerative medicine in clinical trials. However, there are some fundamental questions that remain to be answered prior to successful utilization of BMSSCs in clinical therapy. For instance, how to maintain stemness of BMSSCs will be a critical issue for developing methodologies to propagate multi-potential stem cells in vitro, in order to allow the development of effective clinical therapies.