Current Stem Cell Research & Therapy - Volume 15, Issue 2, 2020

The retinal pigment epithelium (RPE) is a multifunctional monolayer located at the back of the eye required for the survival and function of the light-sensing photoreceptors. In Age-related Macular Degeneration (AMD), the loss of RPE cells leads to photoreceptor death and permanent blindness. RPE cell transplantation aims to halt or reverse vision loss by preventing the death of photoreceptor cells and is considered one of the most viable applications of stem cell therapy in the field of regenerative medicine. Proof-of-concept of RPE cell transplantation for treating retinal degenerative disease, such as AMD, has long been established in animal models and humans using primary RPE cells, while recent research has focused on the transplantation of RPE cells derived from human pluripotent stem cells (hPSC). Early results from clinical trials indicate that transplantation of hPSC-derived RPE cells is safe and can improve vision in AMD patients. Current hPSC-RPE cell production protocols used in clinical trials are nevertheless inefficient. Treatment of large numbers of AMD patients using stem cellderived products may be dependent on the ability to generate functional cells from multiple hPSC lines using robust and clinically-compliant methods. Transplantation outcomes may be improved by delivering RPE cells on a thin porous membrane for better integration into the retina, and by manipulation of the outcome through control of immune rejection and inflammatory responses.

The stem cell exchange during pregnancy is thought to remain chimeras for life. Few studies recently revealed that maternal transfer of viable stem cells to the offspring continues even after birth during breastfeeding. Some of these stem cells are likely to be integrated into different organs (brain, blood, kidneys, and pancreas) including neurons and insulin-producing cells in the pancreas to become functional cells. This finding opens a new avenue for research on therapeutic uses of breast milk- derived stem cells. Recently Dr. Foteini Hassiotou used glowing mice, which were genetically modified to express a gene called tdTomato that causes cells to appear red under fluorescence light. These mice were mated, and their babies were swapped with the pups of another, unmodified mother mouse. The new pups suckled the modified mouse and, as a result, obtained glowing red stem cells from breast milk. The study has never been replicated in humans, so it is not clear yet if the findings apply to humans as in the case of mice. However, the results of the study are the jumping-off points for future research on human breast milk stem cells and their possible application in stem cell therapies. Additional studies are necessary to understand the passage of human breast milk stem cells through the neonate’s GI tract, and passage to the systemic circulation.

Neurodegenerative diseases are progressive and uncontrolled gradual loss of motor neurons function or death of neuron cells in the central nervous system (CNS) and the mechanisms underlying their progressive nature remain elusive. There is urgent need to investigate therapeutic strategies and novel treatments for neural regeneration in disorders like Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Currently, the development and identification of pluripotent stem cells enabling the acquisition of a large number of neural cells in order to improve cell recovery after neurodegenerative disorders. Pluripotent stem cells which consist of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are characterized by their ability to indefinitely self-renew and the capacity to differentiate into different types of cells. The first human ESC lines were established from donated human embryos; while, because of a limited supply of donor embryos, human ESCs derivation remains ethically and politically controversial. Hence, hiPSCs-based therapies have been shown as an effective replacement for human ESCs without embryo destruction. Compared to the invasive methods for derivation of human ESCs, human iPSCs has opened possible to reprogram patient-specific cells by defined factors and with minimally invasive procedures. Human pluripotent stem cells are a good source for cell-based research, cell replacement therapies and disease modeling. To date, hundreds of human ESC and human iPSC lines have been generated with the aim of treating various neurodegenerative diseases. In this review, we have highlighted the recent potentials, advances, and limitations of human pluripotent stem cells for the treatment of neurodegenerative disorders.

Angiogenesis plays a central role in human physiology from reproduction and fetal development to wound healing and tissue repair/regeneration. Clinically relevant therapies are needed for promoting angiogenesis in order to supply oxygen and nutrients after transplantation, thus relieving the symptoms of ischemia. Increase in angiogenesis can lead to the restoration of damaged tissues, thereby leading the way for successful tissue regeneration. Tissue regeneration is a broad field that has shown the convergence of various interdisciplinary fields, wherein living cells in conjugation with biomaterials have been tried and tested on to the human body. Although there is a prevalence of various approaches that hypothesize enhanced tissue regeneration via angiogenesis, none of them have been successful in gaining clinical relevance. Hence, the current review summarizes the recent cell-based and cell free (exosomes, extracellular vesicles, micro-RNAs) therapies, gene and biomaterial-based approaches that have been used for angiogenesis-mediated tissue regeneration and have been applied in treating disease models like ischemic heart, brain stroke, bone defects and corneal defects. This review also puts forward a concise report of the pre-clinical and clinical studies that have been performed so far; thereby presenting the credible impact of the development of biomaterials and their 3D concepts in the field of tissue engineering and regeneration, which would lead to the probable ways for heralding the successful future of angiogenesis-mediated approaches in the greater perspective of tissue engineering and regenerative medicine.

Spinal cord injury (SCI) as a serious public health issue and neurological insult is one of the most severe cause of long-term disability. To date, a variety of techniques have been widely developed to treat central nervous system injury. Currently, clinical treatments are limited to surgical decompression and pharmacotherapy. Because of their negative effects and inefficiency, novel therapeutic approaches are required in the management of SCI. Improvement and innovation of stem cell-based therapies have a huge potential for biological and future clinical applications. Human pluripotent stem cells (hPSCs) including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are defined by their abilities to divide asymmetrically, self-renew and ultimately differentiate into various cell lineages. There are considerable research efforts to use various types of stem cells, such as ESCs, neural stem cells (NSCs), and mesenchymal stem cells (MSCs) in the treatment of patients with SCI. Moreover, the use of patient-specific iPSCs holds great potential as an unlimited cell source for generating in vivo models of SCI. In this review, we focused on the potential of hPSCs in treating SCI.

The nasal septal cartilage plays an important role in the growth of midface and as a vertical strut preventing the collapse of the nasal bones. The repair of nasal cartilage defects remains a major challenge in reconstructive surgery. The tissue engineering strategy in the development of tissue has opened a new perspective to generate functional tissue for transplantation. Given the poor regenerative properties of cartilage and a limited amount of autologous cartilage availability, intense interest has evoked for tissue engineering approaches for cartilage development to provide better outcomes for patients who require nasal septal reconstruction. Despite numerous attempts to substitute the shapely hyaline cartilage in the nasal cartilages, many significant challenges remained unanswered. The aim of this research was to carry out a critical review of the literature on research work carried out on the development of septal cartilage using a tissue engineering approach, concerning different cell sources, scaffolds and growth factors, as well as its clinical pathway and trials have already been carried out.

Stem cell-based regenerative medicine holds exceptional therapeutic potential and hence the development of efficient techniques to enhance control over the rate of differentiation has been the focus of active research. One of the strategies to achieve this involves delivering siRNA into stem cells and exploiting the RNA interference (RNAi) mechanism. Transport of siRNA across the cell membrane is a challenge due to its anionic property, especially in primary human cells and stem cells. Moreover, naked siRNA incites immune responses, may cause off-target effects, exhibits low stability and is easily degraded by endonucleases in the bloodstream. Although siRNA delivery using viral vectors and electroporation has been used in stem cells, these methods demonstrate low transfection efficiency, cytotoxicity, immunogenicity, events of integration and may involve laborious customization. With the advent of nanotechnology, nanocarriers which act as novel gene delivery vehicles designed to overcome the problems associated with safety and practicality are being developed. The various nanomaterials that are currently being explored and discussed in this review include liposomes, carbon nanotubes, quantum dots, protein and peptide nanocarriers, magnetic nanoparticles, polymeric nanoparticles, etc. These nanodelivery agents exhibit advantages such as low immunogenic response, biocompatibility, design flexibility allowing for surface modification and functionalization, and control over the surface topography for achieving the desired rate of siRNA delivery and improved gene knockdown efficiency. This review also includes discussion on siRNA co-delivery with imaging agents, plasmid DNA, drugs etc. to achieve combined diagnostic and enhanced therapeutic functionality, both for in vitro and in vivo applications.

Background: Infertility is a major problem worldwide. Various strategies are being used to develop better treatments for infertility and The most trending strategy is the stem cell therapy. In this study, the literature on stem cell therapy for ovarian disorders is summarized with analysis of current developments. Objective: Different published studies on stem cell-based therapy for the treatment of various types of ovarian insufficiency and disorders such as Premature Ovarian Insufficiency (POI) in the affected female population in animal or human clinical studies are systematically reviewed. Methods: We monitored five databases, including PubMed, Cochrane, Embase, Scopus, and ProQuest. A comprehensive online search was done using the criteria targeting the application of stem cells in animal models for menopause. Two independent reviewers carefully evaluated titles and abstracts of studies. The stem cell type, source, dosage, route of administration were highlighted in various POI animals models. Non-relevant and review articles were excluded. Outcomes: 648 published studies were identified during the initial comprehensive search process from which 41 were selected according to designed criteria. Based on our analysis, stem cells could accelerate ovarian tissues rejuvenation, regulate systemic sex-related hormones levels and eventually increase fertility rate. Conclusion: The evidence suggests that stem cell-based therapies could be considered as an alternative modality to deal with women undergoing POI.