Current Stem Cell Research & Therapy - Volume 11, Issue 1, 2016

Ideal scaffolds for tissue engineering should have the same characteristics and morphology as the tissue. However, the microstructure of many native tissues has anisotropic characteristics, and the extracellular matrix has an orderly arrangement. Thus, aligned biomimetic scaffolds, a class of directional scaffolds, were proposed and researched to further mimic the permutations of tissue. This review covers the biomaterials, technology for the aligned biomimetic scaffolds and applications in tissue engineering. The aligned biomimetic scaffolds are extremely promising for tissue engineering because they can align the directions of cell growth, affect gene expression and significantly enhance cell reprogramming efficiency.

Throughout life, different types of stem cells participate in tissue generation, maintenance, plasticity, and repair. Their abilities to secrete growth factors, to proliferate and differentiate into several cell lineages, and to migrate and home into the damaged tissues have made them attractive candidates for cell therapy and tissue engineering applications. Normal stem cell function is tied to the cell-intrinsic mechanisms and extrinsic signals derived from the surrounding microenvironment or circulation. Understanding the regulatory signals that govern stem cell functions is essential in order to have full knowledge about organogenesis, tissue maintenance and tissue plasticity in the physiological condition. It is also important for optimizing tissue engineering and improving the therapeutic efficiency of stem cells in regenerative medicine. A growing body of evidence indicates that hormonal signals can critically influence stem cell functions in fetal, postnatal, and adult tissues. This review focuses on recent studies revealing how growth hormone, insulin, thyroid hormone, parathormone, adrenocorticotropin, glucocorticoids, erythropoietin, and gastrointestinal hormones control stem cell behavior through influencing survival, proliferation, migration, homing, and differentiation of these cells. Moreover, how environmental factors such as exercise, hypoxia, and nutrition might affect stem cell functions through influencing the endocrine system is discussed. Some of the current limitations of cell therapy and how hormones can help overcoming these limitations are briefly outlined.

Bioreactors are pivotal to the emerging field of tissue engineering. The formation of neotissue from pluripotent cell lineages potentially offers a source of tissue for clinical use without the significant donor site morbidity associated with many contemporary surgical reconstructive procedures. Modern bioreactor design is becoming increasingly complex to provide a both an expandable source of readily available pluripotent cells and to facilitate their controlled differentiation into a clinically applicable ligament or tendon like neotissue. This review presents the need for such a method, challenges in the processes to engineer neotissue and the current designs and results of modern bioreactors in the pursuit of engineered tendon and ligament.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder which is characterized by motor neuron (MN) dysfunction, progressive paralysis, and death. Although several therapeutic approaches have been used for treatment of ALS, little success has been achieved. Natural vectors such as mesenchymal stem cells (MSCs) can be a promising tool for overcoming therapeutic problems. MSCs have multipotential characteristics such as the ability to differentiate into variety of cell types, easy access, immunomodulation, tissue repair, exertion of trophic factors, exosome secretion and efficient homing. In this review, we will discuss the characteristics of MSCs and their possible therapeutic mechanisms in ALS patients.

Mesenchymal stem/stromal cells (MSCs), having both multi-potent differentiation potential and prominent immunomodulatory properties, are seen as a very powerful tool for the therapy of diseases characterized by tissue damage and/or unregulated immune responses. Dendritic cells (DCs) are key immunoregulatory cells at the crossroads between immunity and tolerance, able to fine-tune the whole immune response via regulation of adaptive immunity. Therefore, untangling the complex interactions between DCs and MSCs is crucial for understanding various mechanisms involved in the pathogenesis of immune-related diseases and for the discovery of new therapeutic targets for advanced treatment procedures. From this perspective, we reviewed the data that have been obtained to date regarding the complex effects of MSCs on DC development and functions, delineating the abundant mechanisms involved in these interactions. Additionally, we have pointed out to additional mechanisms of MSC/DC cross-talk that have not been directly proven, but that could have a significant role, not only in DC functions and the maintenance of immune homeostasis, but also in migration, differentiation and the functions of MSCs. For now, much more is known about the influence of MSCs on DCs than vice versa, so more studies should be done in order to fully understand this cross-talk.

Introduction: Studies are needed to understand the role of CD34 expressing cells with regard to efficient engraftment, especially in the adjuvant treatment of cancer. Materials and Methods: In this study we have used a modified method in our laboratory for routinely counting CD34+ cells. Unlysed whole blood samples were stained with the DNA-selective and cell membrane-permeant Vibrant DyeCycle Violet stain. Results: CD34+ cells exhibit a consistent and differential Vybrant Dye Cycle Violet staining pattern. Based on their different DCV intensity, we classified these subpopulations as CD34+/DCVhigh and CD34+/DCVlow cells. In general, DCVhigh cells are about 12-times brighter than DCVlow cells. Conclusion: DCV staining may be used to discriminate subsets of CD34+ cells similarly to other methods which have previously defined different functional properties that can be related to the characterization, resolution, and purification of primitive hematopoietic stem cells in combination with specific useful markers for multicolor flow cytometric measurements.

Inflammatory bowel diseases (IBD) are a collection of diseases associated with chronic inflammation in the intestinal mucosa and/or transmural involvement. IBD is divided into two main categories Crohn’s disease (CD) and ulcerative colitis (UC). While there is no cure for IBD, current therapies can only reduce the inflammatory process that causes the signs and symptoms of IBD and hopefully induce long-term remission. Improved treatment modalities for the complex IBD are still evolving. The increased understanding of the underlying immunopathology has helped identify new targeted treatment options in particular the use of stem cell treatments that are capable of modulating the immune system. Haematopoietic stem cells (HSC) and mesenchymal stromal cells (MSC) therapy are both being investigated as a treatment for IBD. MSC therapy is well tolerated and associated with minimal established side-effects compared to HSC therapy, which involves ablative chemotherapy. Currently, such stem cell therapy is not a standard of care regimen for IBD. However, it may potentially become the next generation treatment of choice, especially for severe refractory IBD patients.

In the present era of stem cell biology, various animals such as Mouse, Bovine, Rabbit and Porcine have been tested for the efficiency of their mesenchymal stem cells (MSCs) before their actual use for stem cell based application in humans. Among them pigs have many similarities to humans in the form of organ size, physiology and their functioning, therefore they have been considered as a valuable model system for in vitro studies and preclinical assessments. Easy assessability, few ethical issues, successful MSC isolation from different origins like bone marrow, skin, umbilical cord blood, Wharton’s jelly, endometrium, amniotic fluid and peripheral blood make porcine a good model for stem cell therapy. Porcine derived MSCs (pMSCs) have shown greater in vitro differentiation and transdifferention potential towards mesenchymal lineages and specialized lineages such as cardiomyocytes, neurons, hepatocytes and pancreatic beta cells. Immunomodulatory and low immunogenic profiles as shown by autologous and heterologous MSCs proves them safe and appropriate models for xenotransplantation purposes. Furthermore, tissue engineered stem cell constructs can be of immense importance in relation to various osteochondral defects which are difficult to treat otherwise. Using pMSCs successful treatment of various disorders like Parkinson’s disease, cardiac ischemia, hepatic failure, has been reported by many studies. Here, in this review we highlight current research findings in the area of porcine mesenchymal stem cells dealing with their isolation methods, differentiation ability, transplantation applications and their therapeutic potential towards various diseases.