Current Stem Cell Research & Therapy - Volume 16, Issue 6, 2021

Development of methods for manipulating and culturing stem cells has enabled the emergence of stem cell therapy as a promising approach in diverse applications, ranging from tissue repair to treatment of intractable diseases such as diabetes, cardiovascular diseases and neurological disorders. Along with technological advances in systemic stem cell delivery, treating multiple injured or pathological sites simultaneously has been made possible. Despite this, most of the works on systemic stem cell transplantation at the moment have focused on the efficiency of tackling local disorders. The prospect of the therapy for enhancing systemic tissue repair, as well as for tackling systemic degenerative disorders, has rarely been seriously considered. The objective of this article is to fill this gap by reviewing the current status of research on systemic stem cell delivery, and by presenting the opportunities and challenges for translating systemic stem cell delivery from the laboratory to the clinic.

Regenerative medicine (RM) is an interdisciplinary field that uses different approaches to accelerate the repair and regeneration or replace damaged or diseased human cells or tissues to achieve normal tissue function. These approaches include the stimulation of the body’s own repair processes, transplantation of progenitor cells, stem cells, or tissues, as well as the use of cells and exosomes as delivery-vehicles for cytokines, genes, or other therapeutic agents. COVID-19 pneumonia is a specific disease consistent with diffuse alveolar damage resulting in severe hypoxemia. Therefore, the most serious cause of death from COVID-19 is lung dysfunction. Here, we consider RM approaches to cure COVID-19 pneumonia based on what RM has so far used to treat lung diseases, injuries, or pneumonia induced by other pathogens. These approaches include stem and progenitor cell transplantation, stem cell-derived exosomes, and microRNAs therapy.

Mesenchymal stromal cells (MSCs) have emerged as a modern development in therapeutics for a wide variety of diseases. Secreted paracrine factors constitute the principal components harboring the restorative promise of MSCs. Recent studies demonstrate that MSC-derived secretomes are composed of several molecules targeting a variety of biological processes that impact tissue repair, growth and immunomodulation. Indeed, secretomes interact with immune cells, activating regulatory anti-inflammatory phenotypes. In this review, we discuss the action of MSC-derived secretomes in promoting tissue regeneration, opposing the inflammatory response in context-specific cases, and treating neurodegenerative diseases, resulting from chronic neuroinflammation.

Oral diseases, such as dental caries, pulpitis, periodontitis, and craniofacial trauma, are common. Some individuals suffer from oral cancer or congenital craniofacial defects. The oral-systemic disease link reveals that a dental disorder is not a minor problem. Tissue loss is an inevitable consequence of most oral diseases, and repairing the tissue loss and restoring craniofacial function are highly expected by patients and are terminal targets of dental treatment. The current clinical approach for tissue loss due to dental caries, pulpitis, periodontitis, oral cancer, trauma, and developmental diseases depends on the filling of corresponding material, allograft, or autograft bone after lesion removal. Repair of the tissue volume is expectedly followed by promising functional restoration using regenerative dental tissue or tissue engineering, which has currently aroused the interest of clinicians and researchers. This review focuses on the ideas and recent findings on newly identified skeletal stem cells (SSCs) as candidates for craniofacial regeneration, signaling regulation of SSCs extended from embryonic development, and signal molecule delivery for the repair of the craniofacial defect, sincerely hoping that the hypothesis of craniofacial self-healing is true in the future.

The E3 ubiquitin ligases Cbl has been found play an important role in regulating cellular proliferation and migration. Whereas, the excessive differentiation of osteoclast and/or its overexpressing of resorptive functions could lead the pathological bone homeostasis by overly bone matrix degradation. Since the first time of the important role of Cbl in the regulating osteoclast differentiation (also named osteoclastogenesis) has been reported in decades ago. The extensively studies have been conducted for in-depth exploring Cbl’s definite role during osteoclastogenesis, as well as its cross talking with other signaling pathways (such as: Src and PI3K signaling) in bone homeostasis. Herein, our current study aims to briefly conclude the current studies of osteoclastogenesis and the regulatory role of Cbl, as well as its cross-talking in bone homeostasis.

Pregnancy and lactation-associated osteoporosis (PLO) is a rare and special form of osteoporosis, which is poorly known with regard to its etiology, pathophysiology and therapy. However, PLO can cause vertebral compression fractures (VCFs) and height loss, which could cause further kyphosis of the spine. Therefore, PLO should be taken into account in the differential diagnosis when a woman presents with severe back pain during or after pregnancy. In our current study, we reviewed the novel literatures that demonstrate the current understanding of and treatment for PLO. In addition, we retrospectively studied four patients who suffered from back pain and VCFs during or after pregnancy. We also examine their clinical medicine treatment methods and outcomes in order to provide evidence for a better understanding of PLO and its relevant medical treatment.

The use of stem cells in cell therapies has shown promising results in the treatment of several diseases, including diabetes mellitus, in both humans and animals. Mesenchymal stem cells (MSCs) can be isolated from various locations, including bone marrow, adipose tissues, synovia, muscles, dental pulp, umbilical cords, and the placenta. In vitro, by manipulating the composition of the culture medium or transfection, MSCs can differentiate into several cell lineages, including insulin-producing cells (IPCs). Unlike osteogenic, chondrogenic, and adipogenic differentiation, for which the culture medium and time are similar between studies, studies involving the induction of MSC differentiation in IPCs differ greatly. This divergence is usually evident in relation to the differentiation technique used, the composition of the culture medium, the cultivation time, which can vary from a few hours to several months, and the number of steps to complete differentiation. However, although there is no “gold standard” differentiation medium composition, most prominent studies mention the use of nicotinamide, exedin-4, mercaptoethanol, fibroblast growth factor b (FGFb), and glucose in the culture medium to promote the differentiation of MSCs into IPCs. Therefore, the purpose of this review is to investigate the stages of MSC differentiation into IPCs both in vivo and in vitro, as well as address differentiation techniques and molecular actions and mechanisms by which some substances, such as nicotinamide, exedin-4, mercaptoethanol, FGFb, and glucose, participate in the differentiation process.

Retinal degenerative diseases (RDDs) are irreversible ocular damages categorized as retinopathies. RDDs affect about 0.05% of individuals worldwide. The degenerations of RPE cells are involved in inherited and age-related RDDs. After the invention of induced pluripotent stem cells (iPSC) by Yamanaka, a promising avenue has been opened to regenerative medicine and disease modeling. Retinal pigment epithelium (RPE) degeneration related-RDDs are also affected by iPSCs. IPSC-derived RPE cells created a novel method for treating the RPE degeneration related- RDDs and retinal diseases modeling to find a new therapeutic approach or drug development. There are various studies based on iPSC-derived RPE cells reporting the investigation of the role of a specific mutation, protein, signaling pathway, etc., responsible for a type of RDD. Furthermore, iPSC-based RPE therapy is expanded to include some clinical trials. Despite the incredible growth rate in iPSC-based studies on RPE-related diseases, there are some challenges, i.e., teratoma formation potential of iPSCs, an expensive procedure of iPSC-based regeneration of RPEs, lack of a universal protocol or cellular product applicable in all patients, etc. This article reviews the iPSC-based RPE generation and their therapeutic applications, studies on RPE-related molecular and cellular pathophysiologic features of RDD in the iPSC-based models, future perspectives, and the challenges ahead.

Temperature is a fundamental factor that affects many functions and structural aspects of physiological systems. Despite its importance, few studies have been performed so far for investigating the compartments and mechanisms engaged in the response of cellular systems to temperature perturbation. In this review, focusing on stem cells, we tried to perform a literature review for investigating the possible ways through which the temperature reduction (hypothermia) affects stem cell function and behavior. Besides, using the obtained results of this investigation, the possible mechanisms are proposed. The survey indicates that profound hypothermia enhances cell adhesion by increasing the stability of E-cadherins. Furthermore, mild hypothermia increases stem cell survival by reducing oxidative stress and prevents apoptosis via the overexpression of anti-apoptotic heat shock proteins. Mild-hypothermia also promotes cell proliferation by affecting gene expression in several ways. Even though it seems that hypothermia generally reduced stem cell differentiation, some inconsistencies are observed between obtained results from the literature. Based on the obtained results, mechanisms responsible for the temperature effect of hypothermia in profound and mild ranges are given that might help the researcher in real experiments.

The potential use of growth factors in stem cell-based therapies for the repair and regeneration of tissues and organs offers a paradigm shift in regenerative medicine. Growth factors are critical signalling molecules that play an important role in tissue development and remodelling. Plasma rich in growth factor (PRGF) is a biotechnological strategy for the harvesting of the active substances of platelets, including growth factors, from the patient’s blood. Because of their tremendous essential growth factor and bioactive agents, as well as their paracrine mechanisms, PRGF has been used as an efficacious option and adjuvant biological therapy in the repair and replacement of damaged organs. This article provides an overview of PRGF extraction and its properties and critically reviewed its clinical benefit and clinical trials in the treatment and regeneration of human organs. Regenerative medicine is a multi-billion-dollar industry with huge interest to clinicians, academics and industries, being considered as an emerging technology.

The past decade has evidenced numerous developments in the treatment of heart diseases; however many patients with chronic heart failure suffer from low quality of life. Therapeutic methods, including drug-delivery as well as heart transplantation, have been used to improve quality of life. Cell therapy and tissue engineering have been recently introduced to the field of medicine as a novel therapeutic approach. Treatment of heart diseases has seen novel development through the introduction of cell therapy approaches. Based on the evidence, cell therapy has emerged as a promising therapeutic strategy for the treatment of cardiac diseases. Since the first cell transplant to patients, different types of (stem) cells have been studied. This study aims to provide a comprehensive review of different types of cells and their roles in cardiac cell-based therapy.