New Advances in Stem Cell Therapy for Osteonecrosis of the Femoral Head
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Osteonecrosis of the femoral head (ONFH) is a common refractory orthopedic disease with multiple etiologies that more frequently occurs in middle-aged and young people. ONFH is the main cause of hip replacement in young patients. Since Professor Hernigou first reported the use of stem cells in the treatment of early stage ONFH, a large number of studies have demonstrated the potential of stem cells in the treatment of adult patients with ONFH. With the rise of interdisciplinary stem cell therapy combined with platelet-rich plasma therapy, gene therapy or other methods have gradually attracted the attention of researchers. This article summarizes the current advances in stem cell therapy for ONFH, as well as the problems and challenges, which may provide reference for further research.Keywords:
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Osteonecrosis of the femoral head (ONFH) is a progressive disease with a complex etiology and unclear pathogenesis, resulting in severe hip pain and dysfunction mainly observed in young patients. Although total hip arthroplasty (THA) is the most effective treatment for patients with ONFH in the terminal stage, the results of THA in young patients or active populations are often not favorable, with some complications related to the prosthesis. With the development of biotechnology, an increasing number of studies pay attention to use of stem cells for the treatment of ONFH. Stem cells are characterized by the ability to self-renew and differentiate into multiple cell types, including differentiation into osteoblasts and endothelial cells to mediate bone repair and angiogenesis. Furthermore, stem cells can offer growth factors to promote blood supply in the necrotic regions by paracrine effects. Therefore, stem cell therapy has become one of the hip-preserving alternatives for ONFH. This review summarized the current trends in stem cell therapy for ONFH, from clinical applications to related basic research, and showed that an increasing number of studies have confirmed the effectiveness of stem cell therapy in ONFH. However, many unsolved problems and challenges in practical applications of stem cell therapy still exist, such as patient selection, standardized procedures, safety assessment, and the fate of transplanted cells in the body. Additional studies are required to find ideal cell sources, appropriate transplantation methods, and the optimal number of cells for transplantation.
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Neuronal death is the common final pathologic pathway of various neurodegenerative diseases (NDs). Although central nervous system has little regenerative potential, it is expected that damaged neural tissue can be recovered by exogenous supplementation of stem cells; however, stem cell therapy cannot modulate specific causes of NDs, such as accumulation of extracellular amyloid peptides in Alzheimer's disease. In contrast, gene therapy can deliver therapeutic genes to specific ND targets. Therefore, combining stem cell and gene therapy would have dual treatment mechanisms (regenerating damaged neural tissue and modifying specific causes of NDs) and lead to better clinical outcomes. In this review, we discuss various therapeutic genes that can be used to develop stem cell gene therapy for various NDs and the techniques for how therapeutic genes can be integrated into stem cells. Keywords: Genetic therapy; Neurodegenerative diseases; Stem cells
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Stem cell therapy for acute myocardial infarction is drawing great attention. However,the biological behavior and function mechanism of implanted stem cells remain controversial, as well as their clinical benefits. With the development of imaging probes and devices, molecular imaging enables noninvasive, dynamic tracking of stem cells in vivo. In this review, we summarize the use of various markers,especially the technique of reporter gene labeling, in the field of stem cell therapy, and highlight some recent preclinical and clinical achievements.
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The loss of sight affects approximately 3.4 million people in the United States and is expected to increase in the upcoming years.(1) Recently, gene therapy and stem cell transplantations have become key therapeutic tools for treating blindness resulting from retinal degenerative diseases. Several forms of autologous transplantation for age-related macular degeneration (AMD), such as iris pigment epithelial cell transplantation, have generated encouraging results, and human clinical trials have begun for other forms of gene and stem cell therapies.(2) These include RPE65 gene replacement therapy in patients with Leber's congenital amaurosis and an RPE cell transplantation using human embryonic stem (ES) cells in Stargardt's disease.(3-4) Now that there are gene therapy vectors and stem cells available for treating patients with retinal diseases, it is important to verify these potential therapies in animal models before applying them in human studies. The mouse has become an important scientific model for testing the therapeutic efficacy of gene therapy vectors and stem cell transplantation in the eye.(5-8) In this video article, we present a technique to inject gene therapy vectors or stem cells into the subretinal space of the mouse eye while minimizing damage to the surrounding tissue.
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The loss of sight affects approximately 3.4 million people in the United States and is expected to increase in the upcoming years.1 Recently, gene therapy and stem cell transplantations have become key therapeutic tools for treating blindness resulting from retinal degenerative diseases. Several forms of autologous transplantation for age-related macular degeneration (AMD), such as iris pigment epithelial cell transplantation, have generated encouraging results, and human clinical trials have begun for other forms of gene and stem cell therapies.2 These include RPE65 gene replacement therapy in patients with Leber's congenital amaurosis and an RPE cell transplantation using human embryonic stem (ES) cells in Stargardt's disease.3-4 Now that there are gene therapy vectors and stem cells available for treating patients with retinal diseases, it is important to verify these potential therapies in animal models before applying them in human studies. The mouse has become an important scientific model for testing the therapeutic efficacy of gene therapy vectors and stem cell transplantation in the eye.5-8 In this video article, we present a technique to inject gene therapy vectors or stem cells into the subretinal space of the mouse eye while minimizing damage to the surrounding tissue.
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Stem Cell-Mediated Gene Delivering for the Treatment of Cerebral Ischemia: Progress and Prospectives
Ischemic stroke is one of the leading causes of death and disability worldwide. There is no effective treatment for ischemic stroke apart from thrombolytic therapy, which has a narrow therapeutic time window. Gene therapy has proven to be effective in experimental stroke, but it suffers from disadvantages that limit its clinical application, such as difficulty in intracranial delivering of therapeutic genes, low efficacy in transfecting host cells and long-term expression of exogenous genes. Delivering therapeutic genes to the ischemic brain via stem cells is an alternative strategy of combined gene and stem cell therapy. There are advantages for stem cell-mediated gene delivery as opposed to direct gene transfer. In recent years, studies used stem cells that over-express different neurotrophic factors, such as BDNF, GDNT, or NT3, and found that the delivery of these genetically-modified stem cells to animal models of ischemic stroke is safe and effective, thus suggesting that stem cell-based gene therapy may be a promising treatment for stroke. This review summarizes the advantages and recent progress of stem cell-based gene therapy for ischemic stroke. We also discuss the relevant strategy for optimizing stem cell-based gene therapy and discuss the potential strategies for its future application. Keywords: Embryonic stem cell, gene therapy, stem cell, ischemic stroke, mesenchymal stem cell, neural stem cell
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Osteonecrosis of the femoral head (ONFH) is a refractory disease that is associated with collapse of the femoral head, with a risk of hip arthroplasty in younger populations. Thus, there has been an increased focus on early interventions for ONFH that aim to preserve the native articulation. Stem cell therapy is a promising treatment, and an increasing number of recent studies have focused on this topic. Many clinical studies have reported positive outcomes of stem cell therapy for the treatment of ONFH. To improve the therapeutic effects of this approach, many related basic research studies have also been performed. However, some issues must be further explored, such as the appropriate patient selection procedure, the optimal stem cell selection protocol, the ideal injection number, and the safety of stem cell therapy. The purpose of this review is to summarize the available clinical studies and basic research related to stem cell therapy for ONFH.
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Stem cell and gene therapy approaches have held out much hope for the development of new tools to treat disease. Therapeutic approaches based on these methods have only rarely found their way into the clinic. The linking of stem cell therapy with selective gene therapy enhances therapeutic options for the regeneration or replacement of diseased or missing cells. This review focuses on the rationale and preliminary results of combining stem cell and gene therapy. Special emphasis is placed on various molecular techniques currently used to genetically engineer stem cells. Viral and nonviral genes delivering technologies are detailed as are techniques for the modulation of gene expression in the context of stem cell recruitment and differentiation. Finally potential clinical applications for this new therapeutic strategy are discussed.
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