Regeneration after stroke: Stem cell transplantation and trophic factors (original) (raw)
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Stem cell transplantation therapy for multifaceted therapeutic benefits after stroke
Progress in neurobiology, 2017
One of the exciting advances in modern medicine and life science is cell-based neurovascular regeneration of damaged brain tissues and repair of neuronal structures. The progress in stem cell biology and creation of adult induced pluripotent stem (iPS) cells has significantly improved basic and pre-clinical research in disease mechanisms and generated enthusiasm for potential applications in the treatment of central nervous system (CNS) diseases including stroke. Endogenous neural stem cells and cultured stem cells are capable of self-renewal and give rise to virtually all types of cells essential for the makeup of neuronal structures. Meanwhile, stem cells and neural progenitor cells are well-known for their potential for trophic support after transplantation into the ischemic brain. Thus, stem cell-based therapies provide an attractive future for protecting and repairing damaged brain tissues after injury and in various disease states. Moreover, basic research on naïve and differe...
Stem Cell Transplantation for Neuroprotection in Stroke
Brain Sciences, 2013
Stem cell-based therapies for stroke have expanded substantially over the last decade. The diversity of embryonic and adult tissue sources provides researchers with the ability to harvest an ample supply of stem cells. However, the optimal conditions of stem cell use are still being determined. Along this line of the need for optimization studies, we discuss studies that demonstrate effective dose, timing, and route of stem cells. We recognize that stem cell derivations also provide uniquely individual difficulties and limitations in their therapeutic applications. This review will outline the current knowledge, including benefits and challenges, of the many current sources of stem cells for stroke therapy.
Cellular and Molecular Life Sciences, 2009
Recent work has focused on cell transplantation as a therapeutic option following ischemic stroke, based on animal studies showing that cells transplanted to the brain not only survive, but also lead to functional improvement. Neural degeneration after ischemia is not selective but involves different neuronal populations, as well as glial and endothelial cell types. In models of stroke, the principal mecha-nism by which any improvement has been observed, has been attributed to the release of trophic factors, possibly promoting endogenous repair mechanisms, reducing cell death and stimulating neurogenesis and angiogenesis. Initial human studies indicate that stem cell therapy may be technically feasible in stroke patients, however, issues still need to be addressed for use in human subjects.
Cell Transplantation Therapy for Stroke
Stroke, 2007
No treatment currently exists to restore lost neurological function after stroke. A growing number of studies highlight the potential of stem cell transplantation as a novel therapeutic approach for stroke. In this review we summarize these studies, discuss potential mechanisms of action of the transplanted cells, and emphasize the need to determine parameters that are critical for transplantation success. (Stroke. 2007;38[part 2]:817-826.) Key Words: clinical trials Ⅲ neural stem/progenitor cells Ⅲ stroke Ⅲ transplantation parameters H uman stem cell transplantation therapy is well established for treating patients with hematopoietic and lymphoid cancers, other blood diseases, and some autoimmune disorders. Clinical stem cell transplant trials for other cancers, heart disease, diabetes, and pediatric traumatic brain injury are currently under way. Moreover, the first human neural stem cell clinical trial has recently been approved for Batten disease, a pediatric lysosomal storage disease that leads to neuronal loss and death. 1 With such advances it becomes important to answer critical questions about the prospects of cell transplantation for stroke therapy. Human Cells Used in Experimental Models of Stroke Recent studies have highlighted the enormous potential of cell transplantation therapy for stroke. A variety of cell types derived from humans have been tested in experimental stroke models, and in many cases some index of behavioral function has been improved (Table 1). Human cells that have been used in these studies fall into 3 categories: (1) neural stem/progenitor cells (NPCs) cultured from fetal tissue; (2) immortalized neural cell lines; and (3) hematopoietic/endothelial progenitors and stromal cells isolated from bone marrow, umbilical cord blood, peripheral blood, or adipose tissue. Neural Stem/Progenitor Cells NPCs and immortalized NPCs grafted into the parenchyma (intracerebrally) surrounding the lesion or delivered intravenously survive, differentiate, and can enhance functional recovery (Table 1). 2-6 With both routes of delivery, cells were found to home to the site of the lesion; this targeted migration may be mediated by injury-induced chemokines such as stromal-derived factor 1 and monocyte chemoattractant protein 1. 7-9 Different preparations of NPCs give rise to varying proportions of neurons and glia after transplantation, but oligodendrocytes were rarely observed (Table 1). This variability in phenotypic fate is probably attributable to both cell intrinsic factors (the developmental potential of different fetal cell preparations) and extrinsic factors (the graft microenvironment) that can affect the outcome of fetal progenitor transplants. There is no obvious correlation between functional recovery and differentiation fate.
Cell transplantation for stroke
Annals of Neurology, 2002
Cell transplantation has emerged as an experimental approach to restore brain function after stroke. Various cell types including porcine fetal cells, stem cells, immortalized cell lines, and marrow stromal cells are under investigation in experimental and clinical stroke trials. This review discusses the unique advantages and limitations of the different graft sources and emphasizes the current, limited knowledge about their biology. The survival, integration, and efficacy of neural transplants in stroke patients will depend on the type, severity, chronicity, adequacy of circulation, and location of the stroke lesion.
Induction of pluripotent stem cells transplantation therapy for ischemic stroke
Molecular and Cellular Biochemistry, 2011
Stroke can cause permanent neurological damage, complications, and even death. However, there is no treatment exists to restore its lost function. Human embryonic stems transplantation therapy was a novel and potential therapeutic approach for stroke. However, as we have seen, the ethical controversy pertains to embryonic stem cell research. Human induced pluripotent stem cells (iPSCs) are the latest generation of stem cells that may be a solution to the controversy of using embryonic cells. In our study, we generated iPSCs from adult human fibroblasts by introduction of four defined transcription factors (Oct4, Sox2, Nanog, and Lin-28). And then, we investigated the efficacy of iPSCs transplantation therapy for stroke on the animal models of middle cerebral artery occlusion. Surprisingly, we found that transplanted iPSCs migrated to injured brain areas, and differentiated into neuron-like cells successfully. After 4-16 days iPSCs grafting, sensorimotor function of rats has been improved significantly. In one word, we may prove that iPSCs therapy in stroke to be an effective form of treatment.
Potential of Stem Cell-Based Therapy for Ischemic Stroke
Frontiers in Neurology, 2018
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.
Cell based therapies for ischemic stroke: From basic science to bedside
Progress in Neurobiology, 2014
Cell therapy is emerging as a viable therapy to restore neurological function after stroke. Many types of stem/progenitor cells from different sources have been explored for their feasibility and efficacy for the treatment of stroke. Transplanted cells not only have the potential to replace the lost circuitry, but also produce growth and trophic factors, or stimulate the release of such factors from host brain cells, thereby enhancing endogenous brain repair processes. Although stem/ progenitor cells have shown a promising role in ischemic stroke in experimental studies as well as initial clinical pilot studies, cellular therapy is still at an early stage in humans. Many critical issues need to be addressed including the therapeutic time window, cell type selection, delivery route, and in vivo monitoring of their migration pattern. This review attempts to provide a comprehensive synopsis of preclinical evidence and clinical experience of various donor cell types, their restorative mechanisms, delivery routes, imaging strategies, future prospects and challenges for translating cell therapies as a neurorestorative regimen in clinical applications.
Recent Advances in Mono- and Combined Stem Cell Therapies of Stroke in Animal Models and Humans
International Journal of Molecular Sciences, 2019
Following the failure of acute neuroprotection therapies, major efforts are currently made worldwide to promote neurological recovery and brain plasticity in the subacute and post-acute phases of stroke. Currently, there is hope that stroke recovery might be promoted by cell-based therapies. The field of stem cell therapy for cerebral ischemia has made significant progress in the last five years. A variety of stem cells have been tested in animal models and humans including adipose stem cells, human umbilical cord blood-derived mesenchymal stem cells, human amnion epithelial cells, human placenta amniotic membrane-derived mesenchymal stem cells, adult human pluripotent-like olfactory stem cells, human bone marrow endothelial progenitor cells, electrically-stimulated human neuronal progenitor cells, or induced pluripotent stem cells (iPSCs) of human origin. Combination therapies in animal models include a mix of two or more therapeutic factors consisting of bone marrow stromal cells, exercise and thyroid hormones, endothelial progenitor cells overexpressing the chemokine CXCL12. Mechanisms underlying the beneficial effects of transplanted cells include the “bystander” effects, paracrine mechanisms, or extracellular vesicles-mediated restorative effects. Mitochondria transfer also appears to be a powerful strategy for regenerative processes. Studies in humans are currently limited to a small number of studies using autologous stem cells mainly aimed to assess tolerability and side-effects of human stem cells in the clinic.