Current Stem Cell Research & Therapy - Volume 9, Issue 3, 2014

Bone and dental tissues in craniofacial region work as an important aesthetic and functional unit. Reconstruction of craniofacial tissue defects is highly expected to ensure patients to maintain good quality of life. Tissue engineering and regenerative medicine have been developed in the last two decades, and been advanced with the stem cell technology. Bone marrow derived mesenchymal stem cells are one of the most extensively studied post-natal stem cell population, and are widely utilized in cell-based therapy. Dental tissue derived mesenchymal stem cells are a relatively new stem cell population that isolated from various dental tissues. These cells can undergo multilineage differentiation including osteogenic and odontogenic differentiation, thus provide an alternative source of mesenchymal stem cells for tissue engineering. In this review, we discuss the important issues in mesenchymal stem cell biology including the origin and functions of mesenchymal stem cells, compare the properties of these two types of mesenchymal cells, update recent basic research and clinic applications in this field, and address important future challenges.

Tissue engineering has yielded several successes in early clinical trials of regenerative medicine with grafting therapeutic cells seeded into biodegradable scaffolds. However this conventional cell delivery method has limited the field’s progress. In recent decades, we have developed a novel cell transferring method, cell sheet technology that allows for controlled attachment and detachment of cells via simple temperature variations of a surface-intelligent temperatureresponsive polymer:poly (N-isopropylacrylamide). It has been widely applied to create functional tissue sheets with cells derived from various tissues to treat a wide range of diseases. Periodontal cell sheets non-invasively harvested from temperature- responsive culture surfaces have been successfully manufactured, resulting in communicative multilayered constructs. Transplantation of cell sheets onto periodontal defects has improved bone and tissue regeneration in animal models and humans and shows low immunogenicity. In this review, we summarize the recent advances of techniques in cell sheet engineering and its application for periodontal regeneration.

The craniofacial region contains a variety of specified tissues, including bones, muscles, cartilages, teeth, blood vessels and nerves. Infections, traumas, genetic, anatomical, or congenital abnormalities could cause tissue defects in the region. Craniofacial tissue engineering and regeneration remain challenging problems for oral and maxillofacial surgeons and scientists. Stem cells isolated from the bone marrow, adipose tissue, dental pulp, the deciduous tooth, or the periodontium were proven to play an important role in tissue regeneration including craniofacial bone defect regeneration, facial nerve regeneration, TMJ (temporal-mandibular joint) condylar cartilage regeneration, TMJ disc regeneration and teeth regeneration in massive studies. In the review, the animal models for craniofacial engineering and regeneration are discussed. Specifically the modalities of establishing a defect model and treatment of the defect with various stem cells in combination with different cytokines and biomaterials are included. The review could be used to choose an appropriate experimental model for specific tissue defect, or to design innovative, reproducible, discriminative experimental models in the future.

Electrospinning has been employed extensively in tissue engineering to generate nanofibrous scaffolds from either natural or synthetic biodegradable polymers. Three-dimensional electrospun scaffolds can create a multi-scale environment capable of facilitating cell adhesion, proliferation, and differentiation. One such multi-scale scaffold incorporates nanofibrous features to mimic the extracellular matrix along with a porous network for the regeneration of a variety of tissues. This review will discuss nanofibrous scaffolds and their tissue-engineering applications in bone, cartilage, periodontium, tooth, and incorporated drug delivery systems. Combination with other technologies, electrospun scaffolds can contribute to the field of craniofacial regeneration and advance technology for tissue-engineered replacements in many physiological systems in near future.

Recent studies have brought endothelial-mesenchymal transition (EndMT) as a special perspective of epithelial- mesenchymal transition (EMT) into eyes. Traditionally, EndMT is considered as a source for fibroblasts and myofibroblasts, and it is extensively investigated in physiologic cardiac development as well as in pathologic tumor and fibrosis. Recently, new studies have found that EndMT-transformed cells had ‘stemness’, which means they could differentiate into chondroblasts, osteoblasts, and adipoblasts in differential culture, respectively. This gives EndMT a bright application future in tissue engineering and regeneration, especially for the formation of cartilage and bone.

The craniofacial region contains many specified tissues, including bone, cartilage, muscle, blood vessels, fat, skin and neurons. A defect or dysfunction of the craniofacial tissue after post-cancer ablative surgery, trauma, congenital malformations and progressive deforming skeletal diseases has a huge influence on the patient’s life. Therefore, functional reconstruction of damaged tissues is highly sought. The use of cell-based therapies represents one of the most advanced methods for enhancing the regenerative response for craniofacial wound-healing. The recently acquired ability to reprogram human adult somatic cells to induced pluripotent stem cells (iPSCs) in culture may provide a powerful tool for in vitro disease modeling and an unlimited source for cell replacement therapy. This review focuses on the generation, biological characterization and discussion of the potential application of iPSCs for craniofacial tissue-engineering applications.

Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) is a member of the polyhydroxyalkanoate (PHA) family. It is the designation of molecules consisting of random co-polymers of 3-hydroxybutyrate and 3- hydroxyhexanoate. PHBHHx plays a significant role in the field of biomedical materials. It has good physical, chemical and mechanical properties, making it potentially useful for a wide range of biomaterials applications. In addition, it has also shown better biocompatibility with different cell types. This paper will introduce the physical, chemical and biological properties of PHBHHx, including biodegradation, hydrophilicity, surface properties and cytocompatibility. The development of PHBHHx in tissue-engineering applications will be discussed. PHBHHx used to repair bone, cartilage, tendons, nerves and vessels will be the focus of discussion.

Disorders in articular cartilage affect many people, and are one of the leading causes of infirmity and decreased quality of life in adults. Tissue engineering and regenerative medicine related to cartilage include a broad range of settings and approaches that seek to repair, augment, replace or regenerate cartilage tissue. Formation of new tissue by cartilageforming cells (chondrogenic cells) is a central feature of each of these goals. Mesenchymal stem cell (MSC) transplantation has been introduced to avoid some of the side-effects and complications of current techniques. Different mesenchymal stem cell sources possess different abilitties to regenerate cartilage. However, the use of MSCs for cartilage repair is still at the stage of preclinical and phase I studies, and no comparative clinical studies have been reported. Therefore, it is difficult to make conclusions in human studies. The focus of this review is the role of MSCs, from different sources in which animal models were involved, in tissue-engineering cartilage repair, and research findings aimed at exploring a more rational application of animal models as the basis for future research, with clinical transformation providing a context.

Neural stem cells (NSCs) are a small subset of primitive precursors that generate and maintain the main phenotypes of the nervous system. Their ability to undergo long-term proliferation and neural differentiation endows them with great potential in regenerative medicine. Therefore, the mechanisms by which NSCs are regulated have been widely explored to improve their therapeutic efficacy in treating neurologic disorders. Recent progress has highlighted the significance of microRNAs (miRNAs) in the regulation of NSC behavior. Thus, to sketch out a comprehensive image of the regulatory mechanisms of miRNAs in NSCs, we here summarize existing evidence of the regulatory roles of diversified miRNAs in the proliferation and neural differentiation of NSCs during embryonic neurodevelopment and adult brain maintenance.

In 2006, Takahashi and Yamanaka first established induced pluripotent stem cells (iPScs). Since then, numerous improvements have been made in the fields of stem cell research, drug research, modelling of diseases, and the treatment of degenerative diseases. Recently, there has been increasing research involving small molecules for evaluating the efficiency of iPSc generation and reducing the risks of heredity as well as oncogenous problems. However, the molecular mechanisms of iPScs remain to be further explored, to meet the demands of practical applications. With a better understanding of degenerative diseases, more complex treatment strategies for novel regenerative medicine are anticipated, and iPSc technology offers an available pathway. This review focuses on the development and application of iPScs.

Cartilage has poor ability of spontaneous repair. Traditional treatments such as microfracture, bone drilling and autologous osteochondral graft were not fully satisfactory to fulfill the clinical needs. The idea of mesenchymal stem cell (MSCs-based cartilage regeneration has been put forward for decades. Large number of studies have been conducted on the biological properties of MSCs, the factors which might facilitate chondrogenic differentiation of MSCs, as well as the scaffold materials for tissue engineering. Promising results have been reported for cartilage repair in animal models. But before massive clinical application of MSCs, more efforts are needed on: differentiation improvement toward mature cartilage chondrocytes instead of hypertrophic chondrocyes and in vitro/in vivo phenotype maintenance; engineering an ideal biomaterial, which can meet the needs of the cartilage regeneration; and performing more studies on critical defects of large animals.

MicroRNAs (miRNAs) are defined as a group of endogenous single-stranded noncoding RNAs that have the ability to downregulate gene expression. Recent research suggests that microRNAs (miRNAs) have a critical role in regulating the self-renewal and differentiation of mesenchymal stem cells (MSCs). MSCs, isolated from various adult tissue sources, are able to differentiate into multiple lineages, which are regulated by genetic and epigenetic mechanisms. Adipose- derived stem cells (ADSCs), originating from the vasculature of adipose tissue, share many properties of bone marrow mesenchymal stem cells (BMSCs). With advantages in both method and quantity of acquisition, ADSCs have become an alternative source of seeding cells. It has been shown that a complex system including various growth factors, transcription factors and signaling pathways could temporally control and regulate MSC differentiation into certain types of mature cells. This review briefly summarizes the biology of miRNAs and ADSCs. We then provide basic information regarding the molecular mechanisms of miRNA regulation in MSC differentiation and discuss several examples of that regulation in ADSC differentiation. Last, we provide perspectives on the progress in identification of the functions of miRNAs in ADSC differentiation.

Due to the ability to differentiate into numerous cell types, multipotent mesenchymal stem cells (MSCs) are currently researched widely including in the field of craniofacial tissues engineering where always requires a wide variety of cell types and tissues while complete surgical reconstruction of craniofacial tissues is always difficult to achieve based on conventional therapies due to such high complexity. Nowadays, numerous animal model studies have been reported on the effect of MSCs in craniofacial tissue engineering including bone, tendon, cartilage, cutaneous wound and vascularization repair etc. Several clinical trials also have been reported with inspiring results. In this review, we will summarize the recent progress of MSCs in craniofacial tissue engineering and the potential clinical application in future.