Current Stem Cell Research & Therapy - Volume 14, Issue 2, 2019

This article presents a special issue of "Current Stem Cell Research & Therapy" devoted to exploring and exploiting tissue engineering through the design of multifunctional therapeutic systems. This lead article draws from twelve contributed articles to discuss the most recent advancements in this emerging field. The common theme in the contributed articles is the emerging therapeutic strategies, and a special appeal is made for collaboration between engineers and biologists for the development of multifunctional therapeutic systems for tissue engineering and regenerative medicine.

In the last few years, the stem cell therapy has gained much popularity among researchers and scientists of biomedical field. It became an effective and alternative approach for the treatment of various physiological conditions (like accidental injuries, burn damage, organ failure, bone marrow transfusion, etc.) and chronic disorders (diabetes, cancer, neurodegenerative disorders, periodontal diseases, etc.). Due to the unique ability of cellular differentiation and regeneration, stem cell therapy serves as the last hope for various incurable conditions and severe damages. The amalgamation of stem cell therapy with nanotechnology brings new prospects to the stem cell research, as it improves the specificity of the treatment and controls the stem cell proliferation and differentiation. In this review article, we have discussed various nanocarrier systems such as carbon nanotubes, quantum dots, nanofibers, nanoparticles, nanodiamonds, nanoparticle scaffold, etc. utilized for the delivery of stem cell inside the body.

Biomedical engineering seeks to enhance the quality of life by developing advanced materials and technologies. Chitosan-based biomaterials have attracted significant attention because of having unique chemical structures with desired biocompatibility and biodegradability, which play different roles in membranes, sponges and scaffolds, along with promising biological properties such as biocompatibility, biodegradability and non-toxicity. Therefore, chitosan derivatives have been widely used in a vast variety of uses, chiefly pharmaceuticals and biomedical engineering. It is attempted here to draw a comprehensive overview of chitosan emerging applications in medicine, tissue engineering, drug delivery, gene therapy, cancer therapy, ophthalmology, dentistry, bio-imaging, bio-sensing and diagnosis. The use of Stem Cells (SCs) has given an interesting feature to the use of chitosan so that regenerative medicine and therapeutic methods have benefited from chitosan-based platforms. Plenty of the most recent discussions with stimulating ideas in this field are covered that could hopefully serve as hints for more developed works in biomedical engineering.

Tissue engineering is a multi-disciplinary field such as material science, life science, and bioengineering that are necessary to make artificial tissue or rejuvenate damaged tissue. Numerous tissue repair techniques and substitute now exist even though it has several shortcomings; these shortcomings give a good reason for the continuous research for more acceptable tissue-engineered substitutes. The search for and use of a suitable stem cell in tissue engineering is a promising concept. Stem cells have a distinctive capability to differentiate and self-renew that make more suitable for cell-based therapies in tissue repair and regeneration. This review article focuses on stem cell for tissue engineering and their methods of manufacture with their application in nerve, bone, skin, cartilage, bladder, cardiac, liver tissue repair and regeneration.

Stem cells are the specialized cell population with unique self-renewal ability and act as the precursor of all the body cells. Broadly, stem cells are of two types one is embryonic stem cells while the other is adult or somatic stem cells. Embryonic stem cells are the cells of zygote of the blastocyst which give rise to all kind of body cells including embryonic cells, and it can reconstruct a complete organism. While the adult stem cells have limited differentiation ability in comparison with embryonic stem cells and it proliferates into some specific kind of cells. This unique ability of the stem cell makes it a compelling biomedical and therapeutic tool. Stem cells primarily serve as regenerative medicine for particular tissue regeneration or the whole organ regeneration in any physical injury or disease condition (like diabetes, cancer, periodontal disorder, etc.), tissue grafting and plastic surgery, etc. Along with this, it is also used in various preclinical and clinical investigations, biomedical engineering and as a potential diagnostic tool (such as the development of biomarkers) for non-invasive diagnosis of severe disorders. In this review article, we have summarized the application of stem cell as regenerative medicine and in the treatment of various chronic diseases.

It is next-to-impossible not to accept that cancer takes a position as the main cause of the global burden of disease, for it is hard to ignore the outnumbered people dying from cancer. Looking at the statistics proves that progress in cancer therapy is always beyond cancer in a race of pessimism about the future; for various kinds of cancers yearly cause death in the world, whereas the conventional and even modern therapies often exhibit lack of reliability in the treatment of cancer. In principle, various reasons are identified for cancer resistance and recurrence. Recognizing the cells/tissue from which cancer takes origin enables its early detection, and optimistically saying, protection of patients against death. It has been recognized that cancer stem cells are responsible for cancer cell proliferation and metastasis. Conventional therapies cannot eradicate the cancer stem cell; therefore, cancer recurrence is unavoidable. In this regards, designing smart platforms with specific properties is an essential step in cancer treatment. Theranostic platforms have facilitated the cancer diagnosis and treatment, simultaneously. In this respect, several types of smart materials have been designed to detect and cure cancer. Cancer stem cell as a root of the cancerous tumor should be eradicated to achieve the complete treatment; hence, cancer stem cell mechanism must be known precisely to design an appropriate platform making possible to encounter with cancer stem cell. In this review paper, various therapeutic and diagnostic techniques of cancerous stem cell are discussed to pave a way for designing proper platforms for cancer eradication.

Diabetes and its complications are a significant health concern throughout the globe. There are physiological differences in the mechanism of type-I and type-II diabetes and the conventional drug therapy as well as insulin administration seem to be insufficient to address the problem at large successfully. Hypoglycemic swings, frequent dose adjustments and resistance to the drug are major problems associated with drug therapy. Cellular approaches through stem cell based therapeutic interventions offer a promising solution to the problem. The need for pancreatic transplants in case of Type- I diabetes can also be by-passed/reduced due to the formation of insulin producing β cells via stem cells. Embryonic Stem Cells (ESCs) and induced Pluripotent Stem Cells (iPSCs), successfully used for generating insulin producing β cells. Although many experiments have shown promising results with stem cells in vitro, their clinical testing still needs more exploration. The review attempts to bring into light the clinical studies favoring the transplantation of stem cells in diabetic patients with an objective of improving insulin secretion and improving degeneration of different tissues in response to diabetes. It also focuses on the problems associated with successful implementation of the technique and possible directions for future research.

Diabetes mellitus is an autoimmune disease which causes loss of insulin secretion producing hyperglycemia by promoting progressive destruction of pancreatic β cells. An ideal therapeutic approach to manage diabetes mellitus is pancreatic β cells replacement. The aim of this review article was to evaluate the role of nanofibrous scaffolds and stem cells in the treatment of diabetes mellitus. Various studies have pointed out that application of electrospun biomaterials has considerably attracted researchers in the field of tissue engineering. The principles of cell therapy for diabetes have been reviewed in the first part of this article, while the usability of tissue engineering as a new therapeutic approach is discussed in the second part.

Background: The pH variation of the injury site is an important factor in the failure of styptic and its structural damage. In this study, the behaviour of a gelatin-silica hybrid in severe bleeding was evaluated under different pH values. On the other hand, the effect of the hybrid particle size, which is one of the key physical properties of the hybrid, has been studied in rapid control of haemostasis. Method: The hybrid haemostatic behaviour varied drastically by changing the particle size, so that the hybrid containing SiO2 with the average particle size of about 1 micro-meter (Hyb Gel-MSiO2) demonstrated very poor ability in platelet adhesion in neutral pH, about 24%. Also, the aPTT was not shorter than the normal time, whereas reduction of the particle size beyond a certain limit (with nanometer SiO2 for Hyb Gel-NSiO2) led to both increasing platelet adhesion to 32% and very considerable reduction of aPTT. Results: Alignment of all results showed that the particle size reduction improves the haemostatic behaviour of the hybrid toward its best performance by controlling excessive bleeding. By changing the pH for a certain particle size, structural integrity, and thereby the hybrid haemostatic behaviour changed dramatically. Therefore, the nano-hybrid showed the most blood absorption (around 470%) in natural pH and acceded to a coherent structure. The results demonstrated that in alkaline or acidic environment, the hybrid haemostatic behaviour was limited. Based on the results of this study, it was found that changes in the hybrid behaviour in acidic pH were much more drastic than in alkaline pH, and also the hybrid with the optimum particle size (Hyb Gel-NSiO2) can maintain the structural integrity with rapid haemostasis (<3 seconds). Conclusion: Based on the objective that the pH at the injury site change to the alkaline side, the resulting hybrid has an excellent ability to control excessive bleeding and can be proposed for further in vivo studies as a novel styptic.

Introduction: One of the serious complications of stroke is memory impairment, which is considered as one of the complications of reperfusion of tissue. The present study was designed to compare the effect of administration of Trolox, carnosic acid and Human Chorionic Gonadotropin (HCG) immediately after reperfusion of the stroke tissue on the memory and hippocampal histology. Method: Ischemia-Reperfusion Model (IRI) was created by bilateral occlusion of the common carotid artery for 15 minutes and the first dose was administered immediately after reperfusion. 10 days after ischemia, passive avoidance memory test and apoptotic protein levels were evaluated. Results: Cerebral Ischemia perfusion reduced the time of latency in entering the dark box in the ischemic group. Administration of Trolox and HCG increased this latency time, while treatment with carnosic acid had no effect. Also, IRI significantly reduced the number of healthy cells in the hippocampus. Administration of Trolox, carnosic acid and HCG increased the number of healthy cells and decreased the expression of Caspase-3 and Bax, but significantly increased the expression of Bcl-2 compared to the ischemic group. Conclusion: Findings indicate the beneficial effects of HCG and Trolox on the improvement of memory and the number of healthy cells in the hippocampal region. It is worth noting that the amount of apoptosis in the hippocampus was significantly reduced by Trolox, HCG and Carnosic acid.

Background and Objective: Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder with consequent cognitive impairment and behavioral deficits. AD is characterized by loss of cholinergic neurons and the presence of beta-amyloid protein deposits. Stem cell transplantation seems to be a promising strategy for regeneration of defects in the brain. Method: One of the suitable type of stem cells originated from fetal membrane is Chorion-derived Mesenchymal Stem Cells (C-MSCs). MSCs were isolated from chorion and characterized by Flowcytometric analysis. Then C-MSCs labeled with DiI were transplanted into the STZ induced Alzheimer disease model in rat. Results: Nissl staining and behavior test were used to assess the efficacy of the transplanted cells. Phenotypic and Flowcytometric studies showed that isolated cells were positive for mesenchymal stem cell marker panel with spindle like morphology. Conclusion: Learning and memory abilities were not improved after stem cell transplantation. C-MSCs transplantation can successfully engraft in injured site but the efficacy and function of transplanted cells were not clinically satisfied.

Background: Cell therapy is an important strategy for the treatment of incurable diseases including those that occur in the Central Nervous System (CNS). Among different strategies, the method of delivering or transplantation of cells into the brain has shown significant effects on regeneration. In this study, a new protocol has been developed for the transplantation of adipose tissuederived stem cells into the brain through Cerebrospinal Fluid (CSF) in rat models. Methods: For this purpose, a wide range of ages (7-30 days old) of male neonates of Wistar rats was used. Moreover, human adipose tissue was obtained from a superficial layer of abdomen through liposuction surgery. The size of the inserted part of needle to access middle cranial fossa and subarachnoid space in animals with an average weight of 10-80 g was determined. In addition, to confirm the entrance of needle into the subarachnoid space, CSF was aspirated slowly and then injection was done within two minutes. Results: The findings showed the presence of transplanted human Adipose-Derived Stem Cells (hADSC) in the cerebellum and basal ganglia following three days and also after two months that confirmed the entrance of transplanted cells into the cerebrospinal fluid and migration of them into the brain tissue. All the animals survived after the transplantation process, with the lowest side effects compared to the available conventional methods. Conclusion: It can be concluded that the cells could be efficiently transplanted into CSF through subarachnoid space by injection via superior orbital fissure with a minimally invasive technique.

Background: Bioactive glasses with different compositions have been extensively used as bone tissue engineering. Preparation, development and characterization of alginate pastes containing bioglass for bone repair applications were the purposes of this study. Objective: The injectable bone pastes were produced from sol-gel derived bioactive glass nanoparticles with various CaO/P2O5 ratios of 19, 9.5 and 4.75 and sodium alginate solutions with different concentrations of 1, 2 and 4 wt.%. The effect of CaO/P2O5 and powder to liquid (P/L) ratios and alginate concentration on injectability, biodegradation, rheological properties, bioactivity and cellular behavior of the pastes have been studied. The behavior of human mesenchymal stem cells (hMSCs) in the presence of the pastes was assessed by MTT assay, biomineralization assay, ALP activity, Acridine orange staining and Alizarin red staining tests. Results: By adding sodium alginate, the pastes exhibited a thixotropy behavior. The storage modulus of all pastes was larger than the loss modulus in the frequency range of 0.1-100 s-1. Cytotoxicity evaluation results revealed that there was a critical amount of bioactive glass in pastes which are above the limit; the viability of hMSCs will be at risk. The pastes made of bioactive glass nanoparticles with CaO/P2O5 = 9.5 and sodium alginate 1% with P/L ratio of 0.8 showed optimum behavior in terms of mineral carrying capacity, injectability characteristics, accellular bioactivity in SBF, loss weight and wash out behavior, proliferation and differentiation of hMSCs. Conclusion: According to the results, the pastes prepared with sodium alginate solution and bioactive glass nanoparticles can be beneficial in bone tissue engineering.