Potential Of Stem Cell-based Therapies Research Articles

Towards Stem/Progenitor Cell-Based Therapies for Retinal Degeneration.

Retinal degeneration (RD) is a leading cause of blindness worldwide and includes conditions such as retinitis pigmentosa (RP), age-related macular degeneration (AMD), and Stargardt's disease (STGD). These diseases result in the permanent loss of vision due to the progressive and irreversible degeneration of retinal cells, including photoreceptors (PR) and the retinal pigment epithelium (RPE). The adult human retina has limited abilities to regenerate and repair itself, making it challenging to achieve complete self-replenishment and functional repair of retinal cells. Currently, there is no effective clinical treatment for RD. Stem cell therapy, which involves transplanting exogenous stem cells such as retinal progenitor cells (RPCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs), or activating endogenous stem cells like Müller Glia (MG) cells, holds great promise for regenerating and repairing retinal cells in the treatment of RD. Several preclinical and clinical studies have shown the potential of stem cell-based therapies for RD. However, the clinical translation of these therapies for the reconstruction of substantial vision still faces significant challenges. This review provides a comprehensive overview of stem/progenitor cell-based therapy strategies for RD, summarizes recent advances in preclinical studies and clinical trials, and highlights the major challenges in using stem/progenitor cell-based therapies for RD.

The potent paracrine effect of umbilical cord mesenchymal stem cells mediates mitochondrial quality control to restore chemotherapy-induced damage in ovarian granulosa cells

The basic principle of chemotherapy is to attack cells with fast growth, and cancer cells are targeted by anticancer drugs because they have a faster growth rate than normal cells. High doses of anticancer drugs may cause an irreversible decline in reproductive capacity, and novel approaches for fertility preservation and/or restoration after anticancer treatment are urgently needed. Here, we provide important insights into the recovery of human reproductive cells damaged by chemotherapy. We performed a detailed screening of the cytokines of various human mesenchymal stem cells (hMSCs) to select superior MSCs. Also, we analyzed the Ovarian granulosa cell (OGC)-)-specific functions for restoring function, apoptosis, and mitochondrial functions to confirm the recovery mechanism in damaged OGCs. As a result, we demonstrated that conditioned media (CM) of Umbilical cord mesenchymal stem cells (UC-MSCs) could restore the functions of damaged OGCs primarily through antiapoptotic and antioxidant effects. Furthermore, CM changed the phenotype of damaged OGCs to an energetic status by restoring mitochondrial function and enhanced the mitochondrial metabolic activity decreased by chemotherapy. Finally, we demonstrated that the restoration of mitochondrial function in damaged OGCs was mediated through mitochondrial autophagy (mitophagy). Our findings offer new insights into the potential of stem cell-based therapy for fertility preservation and/or restoration in female cancer patients.

Overcoming Methodological Challenges for Advancing Stem Cell Therapies in Parkinson's Disease.

The quest for new and improved therapies for Parkinson's disease (PD) remains of paramount importance, despite previous trial failures. There is a current debate regarding the potential of stem cell research as a therapeutic approach for PD. The studies of dopaminergic fetal stem cells for PD treatment, their design, and the results of the initial surgical placebo-controlled trials were reviewed in this study. Some of the fundamental methodological challenges and possible strategies to resolve them were proposed. In this article, we argue that the most important impact lies in the proof-of-principle demonstrated by clinical trials for cell replacement strategies in reconstructing the human brain. While some researchers argue that the considerable technical challenges associated with cell therapies for PD warrant the discontinuation of further development using stem cells, we believe that the opposing viewpoints are instrumental in identifying a series of methodological misunderstandings. Here, we propose to expose key challenges to ensure the advancement of the field and unlock the potential of stem cell therapies in PD treatment. Overall, this review underscores the need for further research and innovation to overcome the hurdles in realizing the potential of stem cell-based therapies for PD.

Advancements and mechanisms of stem cell-based therapies for spinal cord injury in animals.

Spinal cord injury (SCI) is a neurodegenerative disorder of the central nervous system (CNS) that can lead to permanent loss of sensation and voluntary movement beyond the affected area. Extensive preclinical and clinical trials have been conducted to evaluate the safety and effectiveness of stem cells for the treatment of various CNS diseases or disorders, including SCI. However, several challenges hinder nerve cell regeneration in the injured spinal cord, such as extensive cell loss, limited neural cell regeneration capacity, axonal disruption, and the presence of growth-inhibiting molecules, particularly astroglial scarring or glial scars at the injury site in chronic cases. These obstacles pose significant challenges for physicians in restoring normal motor and sensory nerve function in both humans and animals following SCI. This review focuses on SCI pathogenesis, the mechanisms underlying the therapeutic potential of Mesenchymal Stem Cells (MSCs) in SCI, and the potential of stem cell-based therapies as promising avenues for treatment. This review article also included relevant preclinical and clinical data from animal studies.

CELL CROSS TALK IN DISEASES: THE INTERPLAY BETWEEN STEM CELLS AND SOME INFECTIOUS DISEASES, THERAPEUTIC PROSPECTS IN LOW-INCOME COUNTRIES

Particularly in low-income nations, infectious illnesses continue to be a significant global health burden. The interaction of stem cells with infectious diseases has become a fascinating field of study with bright therapeutic potential. This review article seeks to give readers an overview of how cells interact with one another in disease, with a particular focus on how stem cells interact with a few specific infectious diseases and their therapeutic potential in low-income nations. The definition and several types of stem cells are introduced at the outset of the review, with a focus on their capacity for regeneration and immunomodulation. The significance of stem cells in tissue repair and regeneration is next discussed, emphasizing their potential to lessen the damaging effects of infectious illnesses on host tissues.The article also examines the behaviour and function of stem cells as well as the direct and indirect effects of pathogens on stem cells. Examining the immune systems function in controlling the interaction between infections and stem cells helps to understand the intricate cellular cross-talk involved. The review examines the therapeutic potential of stem cell-based therapies for infectious diseases in the context of low-income nations. It addresses the potential of stem cell treatments for conditions like HIV, malaria, tuberculosis, and neglected tropical diseases while highlighting the developments and difficulties associated with applying these treatments in settings with limited resources.Overall, this review demonstrates the complex relationship between stem cells and infectious diseases and offers insights into the potential therapeutic applications of stem cell-based therapies in low-income nations. It emphasizes the requirement for additional study, teamwork, and the creation of affordable and widely available stem cell therapies to effectively combat infectious diseases and enhance healthcare outcomes in settings with limited resources.

Exploring the potential of stem cell-based therapy for aesthetic and plastic surgery.

Over the last decade, stem cell-associated therapies are widely used because of their potential in self-renewable and multipotent differentiation ability. Stem cells have become more attractive for aesthetic uses and plastic surgery, including scar reduction, breast augmentation, facial contouring, hand rejuvenation, and anti-aging. The current preclinical and clinical studies of stem cells on aesthetic uses also showed promising outcomes. Adipose-derived stem cells are commonly used for fat grafting that demonstrated scar improvement, anti-aging, skin rejuvenation properties, etc. While stem cell-based products have yet to receive approval from the FDA for aesthetic medicine and plastic surgery. Moving forward, the review on the efficacy and potential of stem cell-based therapy for aesthetic and plastic surgery is limited. In the present review, we discuss the current status and recent advances of using stem cells for aesthetic and plastic surgery. The potential of cell-free therapy and tissue engineering in this field is also highlighted. The clinical applications, advantages, and limitations are also discussed. This review also provides further works that need to be investigated to widely apply stem cells in the clinic, especially in aesthetic and plastic contexts.

Potential of Stem Cell-Based Therapy to Restore Function in Aging Systems: Are We There Yet?

While there is extensive interest in geroscience approaches to health and disease, few basic science discoveries have made their way into clinical trials. Herein, we comment on cell-based therapies, in which supplementing robust stem cell capacity to aged systems theoretically could lead to sustained improvement. This exciting approach has undergone translational development, and we highlight studies targeting a single system and others aimed at treating overall aging frailty by restoring the aged stem cell niches that underly diminished endogenous regenerative capacity.

Stem Cells and Dentofacial Orthodontic Treatment Potential

Background: In recent years, stem cell therapy has become a very promising and advanced scientific research topic. With advanced technology in tissue engineering, the development of this approach has evolved with great expectations.Methods: This article is focused on the discovery of stem cells and their potential application in dentofacial orthodontic treatment. For craniofacial deformities, stem cell-based therapy has been applied as a part of a tissue engineering approach to regenerate bone and tissues to reconstruct the deformities. With a limitation of tissue defects, several stem cells could be great candidates for the treatment.Conclusions: Stem cell-based therapy could be applied for TMJ regeneration with great potential for the development of scaffold regenerative materials. Current evidence demonstrates the potential of stem cellbased therapy for regenerate cementum, collagen and alveolar bone for the benefit of accelerated tooth movement, increased envelope of discrepancy and improved posttreatment stability.Practical implications: However, there is a need for more in vivo and clinical trials for stem cell-based therapy to be used as a standard treatment.

Smart graphene-based hydrogel promotes recruitment and neural-like differentiation of bone marrow derived mesenchymal stem cells in rat skin.

Strategies to direct the differentiation of endogenous bone marrow derived mesenchymal stem cells (BMSCs) in vivo following recruitment to the injured site are critical to realizing the potential of stem cell-based therapies. But the differentiation efficiency of BMSCs remains limited without direction. Here we demonstrated a novel strategy to promote neuronal differentiation of BMSCs using cross-linked polyethylenimine (PEI) grafted graphene oxide (GO) as the enzyme responsive vector for delivering active genes to BMSCs. In vivo, a core-shell microfiber arrayed hydrogel with a chemokine (SDF-1α) and the cross-linked GO-PEI/pDNAs-bFGF microparticles incorporated into the shell and core, respectively, were constructed. The arrayed hydrogel was shown to recruit and stimulate the neural-like differentiation of BMSCs effectively by delivering the CXCL12 and GO-PEI/pDNAs-bFGF in a self-controlled manner. With this strategy, both in vitro and in vivo neuronal differentiation of BMSCs with function were accelerated significantly. The cross-linked GO-PEI mediated gene transfection together with a multi-functional microfiber arrayed hydrogel provide a translatable approach for endogenous stem cell-based regenerative therapy.

Mesenchymal stromal/stem cells: historical perspective and ongoing challenges

The potential of stem cell-based therapy was accompanied by high expectations and led, consequently, to an increase in clinical translational investments. Mesenchymal stem/stromal cells (MSCs) became the cell-based product most experimentally studied worldwide. However, uncertainties about the mechanisms and the in vivo identity of MSCs impose concerns about their large-scale use in regenerative medicine. This review comprises a historical summary on MSC, a critical discussion about their identity and function, and the ongoing challenges for their use in therapy and tissue bioengineering.

CORR Synthesis: What Is the Evidence for the Clinical Use of Stem Cell-based Therapy in the Treatment of Osteoarthritis of the Knee?

CORR Synthesis: What Is the Evidence for the Clinical Use of Stem Cell-based Therapy in the Treatment of Osteoarthritis of the Knee?

Cost-Effective, Safe, and Personalized Cell Therapy for Critical Limb Ischemia in Type 2 Diabetes Mellitus.

Cell therapy is a progressively growing field that is rapidly moving from preclinical model development to clinical application. Outcomes obtained from clinical trials reveal the therapeutic potential of stem cell-based therapy to deal with unmet medical treatment needs for several disorders with no therapeutic options. Among adult stem cells, mesenchymal stem cells (MSCs) are the leading cell type used in advanced therapies for the treatment of autoimmune, inflammatory and vascular diseases. To date, the safety and feasibility of autologous MSC-based therapy has been established; however, their indiscriminate use has resulted in mixed outcomes in preclinical and clinical studies. While MSCs derived from diverse tissues share common properties depending on the type of clinical application, they markedly differ within clinical trials in terms of efficacy, resulting in many unanswered questions regarding the application of MSCs. Additionally, our experience in clinical trials related to critical limb ischemia pathology (CLI) shows that the therapeutic efficacy of these cells in different animal models has only been partially reproduced in humans through clinical trials. Therefore, it is crucial to develop new research to identify pitfalls, to optimize procedures and to clarify the repair mechanisms used by these cells, as well as to be able to offer a next generation of stem cell that can be routinely used in a cost-effective and safe manner in stem cell-based therapies targeting CLI.

Concise Review: Intercellular Communication Via Organelle Transfer in the Biology and Therapeutic Applications of Stem Cells.

The therapeutic potential of stem cell-based therapies may be largely dependent on the ability of stem cells to modulate host cells rather than on their differentiation into host tissues. Within the last decade, there has been considerable interest in the intercellular communication mediated by the transfer of cytoplasmic material and organelles between cells. Numerous studies have shown that mitochondria and lysosomes are transported between cells by various mechanisms, such as tunneling nanotubes, microvesicles, and cellular fusion. This review will focus on the known instances of organelle transfer between stem cells and differentiated cells, what effects it has on recipient cells and how organelle transfer is regulated. Stem Cells 2019;37:14-25.

Co-Transplant of Parathyroid Gland and Stem Cell-Derived Insulin-Producing Cells Enhances Graft Survival through Release of Pro-Angiogenic and Pro-Survival Factors

Introduction Ischemia dramatically impairs survival and function of islets after transplantation. Human Stem Cell-derived Beta Cells are currently being tested in clinical trials for replacement therapy. Although stem cell technology represents an unlimited source of beta cells, it is paramount to reduce the effects of ischemia to optimize outcome. Parathyroid glands (PTG) are known to engraft in the subcutaneous and intra-muscular sites with high success rate. The objective of this study is to investigate if PTG can protect beta-cell grafts. We hypothesize that PTG protect beta cells by both accelerating neo-vasculogenesis and by producing tropic factors that sustain beta cell viability before revascularization. Methods Stem Cell-derived Beta Cells were produced from a human embryonic stem cell line with a GFP transgene knocked into the insulin locus and a constitutively expressed luciferase transgene. Insulin-producing GFP+ cells were enriched by FACS and reaggregated to form enhanced beta clusters (eBCs). eBC were transplanted under the subcutaneous space (SQ) of NSG mice and graft mass was monitored using bioluminescence imaging. Human PTG were finely cut and co-transplanted with eBC. PTG-derived CD34+ and CD34- cells were FACS purified, cultured for 24 hours and supernatants were assessed for cytokines using Luminex. Effects of PTG-derived factors on eBCs viability after challenges of hypoxia and nutrient deprivation were assessed in vitro. Results and Discussion eBC graft mass decreased by 60% in two weeks after transplant under the SQ. However, when eBC grafts were co-transplanted with PTG, bioluminescent signal increased up to 150% (Figure 1 A and B). We further investigated the mechanisms of PTG protection. We found PTG-derived CD34+ cells produced CCL2, CXCL12, VEGF-A, and PDGF-AA (Figure 2), which have all been previously implicated in neo-vasculogenesis. Consistently, PTG co-transplant led to a dramatic increase in the ingrowth of CD31+ cells. Additionally, PTG secreted parathyroid hormone (PTH), parathyroid hormone-related protein (PTHrP), and γ-aminobutyric acid (GABA). These factors improved eBC survival during in vitro-simulated ischemia challenge using nutrient-deprivation and/or hypoxia (Figure 3). Conclusions Our results show that PTG co-transplantation preserves beta cell graft survival. PTG-derived CD34+ cells promote neovascularization of eBC grafts by producing angiogenic factors. PTG may also have direct cytoprotective effects on eBCs by producing PTH, PTHrP, and GABA. These properties of PTG may be harnessed to minimize ischemic injury to eBC after transplant to realize the therapeutic potential of stem cell-based therapy for diabetes.

Potential of Stem Cell-Based Therapy for Ischemic Stroke.

Ischemic stroke is one of the major health problems worldwide. The only FDA approved anti-thrombotic drug for acute ischemic stroke is the tissue plasminogen activator. Several studies have been devoted to assessing the therapeutic potential of different types of stem cells such as neural stem cells (NSCs), mesenchymal stem cells, embryonic stem cells, and human induced pluripotent stem cell-derived NSCs as treatments for ischemic stroke. The results of these studies are intriguing but many of them have presented conflicting results. Additionally, the mechanism(s) by which engrafted stem/progenitor cells exert their actions are to a large extent unknown. In this review, we will provide a synopsis of different preclinical and clinical studies related to the use of stem cell-based stroke therapy, and explore possible beneficial/detrimental outcomes associated with the use of different types of stem cells. Due to limited/short time window implemented in most of the recorded clinical trials about the use of stem cells as potential therapeutic intervention for stroke, further clinical trials evaluating the efficacy of the intervention in a longer time window after cellular engraftments are still needed.

Ethical and Safety Issues of Stem Cell-Based Therapy.

Results obtained from completed and on-going clinical studies indicate huge therapeutic potential of stem cell-based therapy in the treatment of degenerative, autoimmune and genetic disorders. However, clinical application of stem cells raises numerous ethical and safety concerns.In this review, we provide an overview of the most important ethical issues in stem cell therapy, as a contribution to the controversial debate about their clinical usage in regenerative and transplantation medicine.We describe ethical challenges regarding human embryonic stem cell (hESC) research, emphasizing that ethical dilemma involving the destruction of a human embryo is a major factor that may have limited the development of hESC-based clinical therapies. With previous derivation of induced pluripotent stem cells (iPSCs) this problem has been overcome, however current perspectives regarding clinical translation of iPSCs still remain. Unlimited differentiation potential of iPSCs which can be used in human reproductive cloning, as a risk for generation of genetically engineered human embryos and human-animal chimeras, is major ethical issue, while undesired differentiation and malignant transformation are major safety issues.Although clinical application of mesenchymal stem cells (MSCs) has shown beneficial effects in the therapy of autoimmune and chronic inflammatory diseases, the ability to promote tumor growth and metastasis and overestimated therapeutic potential of MSCs still provide concerns for the field of regenerative medicine.This review offers stem cell scientists, clinicians and patient's useful information and could be used as a starting point for more in-depth analysis of ethical and safety issues related to clinical application of stem cells.

Nanoparticle-mediated transcriptional modification enhances neuronal differentiation of human neural stem cells following transplantation in rat brain

Strategies to enhance survival and direct the differentiation of stem cells in vivo following transplantation in tissue repair site are critical to realizing the potential of stem cell-based therapies. Here we demonstrated an effective approach to promote neuronal differentiation and maturation of human fetal tissue-derived neural stem cells (hNSCs) in a brain lesion site of a rat traumatic brain injury model using biodegradable nanoparticle-mediated transfection method to deliver key transcriptional factor neurogenin-2 to hNSCs when transplanted with a tailored hyaluronic acid (HA) hydrogel, generating larger number of more mature neurons engrafted to the host brain tissue than non-transfected cells. The nanoparticle-mediated transcription activation method together with an HA hydrogel delivery matrix provides a translatable approach for stem cell-based regenerative therapy.

Editorial: Stem cells and progenitor cells in ischemic stroke—fashion or future?

Editorial: Stem cells and progenitor cells in ischemic stroke—fashion or future?

A laser-induced mouse model with long-term intraocular pressure elevation.

PurposeTo develop and characterize a mouse model with intraocular pressure (IOP) elevation after laser photocoagulation on the trabecular meshwork (TM), which may serve as a model to investigate the potential of stem cell-based therapies for glaucoma.MethodsIOP was measured in 281 adult C57BL/6 mice to determine normal IOP range. IOP elevation was induced unilaterally in 50 adult mice, by targeting the TM through the limbus with a 532-nm diode laser. IOP was measured up to 24 weeks post-treatment. The optic nerve damage was detected by electroretinography and assessed by semiautomatic counting of optic nerve axons. Effects of laser treatment on the TM were evaluated by histology, immunofluorescence staining, optical coherence tomography (OCT) and transmission electron microscopy (TEM).ResultsThe average IOP of C57BL/6 mice was 14.5±2.6 mmHg (Mean ±SD). After laser treatment, IOP averaged above 20 mmHg throughout the follow-up period of 24 weeks. At 24 weeks, 57% of treated eyes had elevated IOP with the mean IOP of 22.5±2.5 mmHg (Mean ±SED). The difference of average axon count (59.0%) between laser treated and untreated eyes was statistically significant. Photopic negative response (PhNR) by electroretinography was significantly decreased. CD45+ inflammatory cells invaded the TM within 1 week. The expression of SPARC was increased in the TM from 1 to 12 weeks. Histology showed the anterior chamber angle open after laser treatment. OCT indicated that most of the eyes with laser treatment had no synechia in the anterior chamber angles. TEM demonstrated disorganized and compacted extracellular matrix in the TM.ConclusionsAn experimental murine ocular hypertension model with an open angle and optic nerve axon loss was produced with laser photocoagulation, which could be used to investigate stem cell-based therapies for restoration of the outflow pathway integrity for ocular hypertension or glaucoma.

The potential of stem cell-based therapy for retinal repair.

Like injured neurons in the brain or spinal cord, neurons in the retina are incapable to regenerate following injury and ultimately would lead to irreversible neuronal loss and vision impairment. Over decades, extensive effort has been made to develop strategies to protect retinal neurons from death; however, the outcome is limited (Pettmann and Henderson, 1998; Bahr, 2000; Lagali and Picketts, 2011). Replacing the degenerated retinal neurons by newly generated and functional neurons would be an ideal scenario. The rapid development of stem cell biology has recently demonstrated that stem cells could be a potential source of cells for cell replacement therapy because these cells have the self-renewal capacity and could be differentiated into many cell types. This review will discuss the therapeutic potential of stem cell-based therapy to retinal degenerative diseases.