Cell Therapy For Stroke Research Articles

Challenges and possibilities of intravascular cell therapy in stroke.

Stroke is the third leading cause of death in Western countries and more importantly a leading cause of adult disability. The recovery process of stroke patients might be enhanced by intensive rehabilitation, which acts through brain plasticity mechanisms. Restorative approaches such as cell-based therapies are clinically appealing as it might be possible to help patients even when treatment is initiated days or weeks after the ischemic insult. An extensive number of experimental transplantation studies have been conducted with cells of different origins (e.g., embryonic stem, fetal neural stem, human umbilical cord blood) with promising results. Noninvasive intravascular administration of cells, which provides a broad distribution of cells to the close proximity of ischemic tissue, has perhaps the most immediate access to clinical applications. However, surprisingly little is known about whole body biodistribution of intravascularly administered cells and mechanisms leading to improved functional recovery. This review examines the recent literature concerning intravascular cell-based therapies in experimental stroke.

Amnion: A Potent Graft Source for Cell Therapy in Stroke

Regenerative medicine is a new field primarily based on the concept of transplanting exogenous or stimulating endogenous stem cells to generate biological substitutes and improve tissue functions. Recently, amnion-derived cells have been reported to have multipotent differentiation ability, and these cells have attracted attention as a novel cell source for cell transplantation therapy. Cells isolated from amniotic membrane can differentiate into all three germ layers, have low immunogenicity and anti-inflammatory function, and do not require the destruction of human embryos for their isolation, thus circumventing the ethical debate commonly associated with the use of human embryonic stem cells. Accumulating evidence now suggests that the amnion, which had been discarded after parturition, is a highly potent transplant material in the field of regenerative medicine. In this report, we review the current progress on the characterization of MSCs derived from the amnion as a remarkable transplantable cell population with therapeutic potential for multiple CNS disorders, especially stroke.

Cell Therapy for Stroke

Stroke remains a significant clinical unmet condition, with only 3% of ischemic patient population benefiting from the thrombolytic drug tissue plasminogen activator largely because of the drug's narrow 3-hour therapeutic window. Extending the stroke therapeutic window will greatly impact on treatment, care, and management of patients. Summary of Review- Cell therapy is appealing in this regard as it widens the stroke treatment opportunity by targeting the neurorestorative phase (ie, several hours to days and even weeks or months after stroke). Although compelling preclinical evidence reveals that transplantation of stem/progenitor cells is safe and effective in animal models of stroke, the laboratory data need to be evaluated on their translational relevance for clinical application. In addressing this issue, I borrow heavily from the conference proceedings of the 2007 STEPS (Stem Cell Therapeutics as an Emerging Paradigm in Stroke). Translational research guidelines are being adapted by academic institutes, industry, National Institutes of Health (NIH), and Food and Drug Administration (FDA), and adhering to these preclinical criteria will provide the basis for advancing cell therapy in stroke from the laboratory to the clinic.

Stem cell therapy in stroke.

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 mechanism 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.

Is there room for regeneration: Spontaneous versus induced neurogenesis

Stroke is a common disorder and one of the leading causes of death and disability in humans. In stroke, occlusion of a cerebral artery leads to focal ischemia in a restricted central nervous system region and death of different types of cells. Treatments to support efficient functional recovery in stroke patients are lacking. Cells from different sources have been tested for their ability to reconstruct the forebrain and improve function after transplantation in animals subjected to stroke. The transplanted cells can survive and partly reverse some behavioral deficits. However, the underlying mechanisms are unclear and there is little evidence for neuronal replacement. Recent findings in rodents that stroke leads to increased generation of neurons endogenous precursors in the subventricular zone, suggest an alternative approach to cell therapy in stroke based on regeneration. Stroke-generated new neurons, as well as neuroblasts probably already formed before the insult, migrate into the partially and severely damaged area of the striatum, where they express markers of developing and mature striatal medium-sized spiny neurons. Thus, the new neurons seem to differentiate into the phenotype of most neurons destroyed by the ischemic lesion. Majority of the new neurons die at early stages of their development most likely through apoptotic mechanism, and they only replace a relatively small fraction of the died mature striatal neurons. However, regeneration and re-establishment even of only a small part of damaged neuronal circuitries could have significant implications and support functional recovery. Several factors can induce or promote adult neurogenesis by stimulating formation and/or improving survival of new neurons, e. g., FGF-2, stem cell factor, erythropoietin, BDNF, caspase inhibitors, and anti-inflammatory drugs. Different hormones, environmental factors and physiological stimuli can also modulate adult neurogenesis. Whether the new neurons formed after stroke establish connections with other neurons is not known, though BDNF-generated new neurons in the intact striatum seem to form afferent and efferent connections. There is no significant formation of new neurons in the cerebral cortex after stroke. However, targeted apoptotic degeneration of cortical neurons in mice, leaving tissue architecture intact, leads to formation of new cortical neurons extending axons to the thalamus. Thus, restricted self-repair capacity in ischemically damaged cortex is probably due to lack of cues necessary to trigger neurogenesis from putative local parenchymalneural stem cells or migration of neuroblasts from subventricular zone. If new stroke-generated striatal neurons are fully integrated in the neuronal circuitry and their formation can be stimulated, this could lead to the development of a novel therapeutic strategy for stroke in humans.

Adult stem cell therapy in stroke

Acute cerebral infarction causes irreversible locally restricted loss of the neuronal circuitry and supporting glial cells with consecutive functional deficits and disabilities. The currently available and effective therapy targets fast vessel recanalization accompanied by symptomatic measures. Research activities focusing on stem cells, which represent a promising source for organotypic cell replacement and functional recovery after stroke, have gained momentum in recent years, making regenerative cell-based therapies a much more feasible realistic approach. This review provides an update about preclinical and clinical cell-based studies in stroke focusing on stem cells derived from the adult central nervous and hematopoetic systems. Endogenous neural stem cells, which have been shown to reside throughout life in the central nervous system, have the capacity to replace lost neurons in models for numerous disorders, including cerebral ischemia. Considering adult neural stem cell transplantation as a regenerative strategy after stroke, progress has been made in isolating human adult neural stem cells and demonstrating the feasibility of autologous neural stem cell transplantation. An increasing number of studies provide evidence that hematopoietic stem cells, either after stimulation of endogenous stem cell pools or after exogenous hematopoietic stem cell application (transplantation), improve functional outcome after ischemic brain lesions. Various underlying mechanisms such as transdifferentiation into neural lineages, neuroprotection through trophic support, and cell fusion have been deciphered. Many preclinical studies employing adult stem cell-based strategies hold great promise. For endogenous approaches the correlate of cell replacement underlying functional improvement needs to be demonstrated. Transplantation approaches on the experimental level need further development before clinical application can be considered.

Cell Therapy for Stroke

Increasing experimental evidence suggests that cell transplantation can enhance recovery from stroke in animal models of focal cerebral ischemia. Clinical trials have been investigating the effects of a human immortalized neuronal cell line and porcine fetal neurons in stroke victims with persistent and stable deficits. Preclinical studies are focusing on the effects of human stem cells from various sources including brain, bone marrow, umbilical cord, and adipose tissue. This review presents an overview of preclinical and clinical studies on cell therapy for stroke. We emphasize the current, limited knowledge about the biology of implant sources and discuss special conditions in stroke that will impact the potential success of neurotransplantation in clinical trials.

Cell therapy for stroke

Cell therapy for stroke