Stem Cell Therapy For Treatment Research Articles

Development of an allogeneic adherent stem cell therapy for treatment of ischemic stroke

To determine the potential for using stem cells in the treatment of ischemic injuries of the central nervous sys- tem, clinically relevant experiments were performed administering human adult adherent bone marrow derived stem cells into a rat model of ischemic stroke. Variables such as the requirement for immunosuppression, route of cell administration, window for therapeutic benefit and optimal cell dosage have all been examined in a series of relevant translational experiments in animals undergoing middle cerebral artery ligation stroke injury. Animals were tested for improvements in locomotor and neurological function at time points as late as 6 months post-cell transplantation and demonstrated sustained statistically significant benefit from a single dose of cells. Following sacrifice, immunohistochemistry was performed on tissues to determine stem cell engraftment and fate, as well as neuroprotection of endogenous tissue at the sites of ischemic injury. The results indicate locomotor and neu- rological improvement correlates with improved neuroprotection and limited retention of the transplanted stem cells, with limited neuronal fate. The observed benefit occurs in a cell dosage dependent fashion suggesting a pharmacological role for the cells when administered intravenously in these injury models.

Development of an allogeneic adherent stem cell therapy for treatment of ischemic stroke

Development of an allogeneic adherent stem cell therapy for treatment of ischemic stroke

Successful Clinical Implementation of Corneal Epithelial Stem Cell Therapy for Treatment of Unilateral Limbal Stem Cell Deficiency

The corneal epithelium is maintained by a population of stem cells known as limbal stem cells (LSCs) due to their location in the basal layer of the outer border of the cornea known as the limbus. Treatment of limbal stem cell deficiency (LSCD) has been achieved with transplantation of ex vivo expanded LSCs taken from a small biopsy of limbus. This is a relatively new technique, and as such, specific national or international guidance has yet to be established. Because of the lack of such specific guidance, our group has sought to minimize any risk to the patient by adopting certain modifications to the research methodologies in use at present. These include the replacement of all non-human animal products from the culture system and the production of all reagents and cultures under Good Manufacturing Practice conditions. In addition, for the first time, a strictly defined uniform group of patients with total unilateral LSCD and no other significant ocular conditions has been used to allow the success or failure of treating LSCD to be attributable directly to the proposed stem cell therapy. A prospectively designed study with strict inclusion and exclusion criteria was used to enroll patients from our database of patients with unilateral LSCD. Eight eyes of eight consecutive patients with unilateral total LSCD treated with ex vivo expanded autologous LSC transplant on human amniotic membrane (HAM) with a mean follow-up of 19 (RANGE) months were included in the study. Postoperatively, satisfactory ocular surface reconstruction with a stable corneal epithelium was obtained in all eyes (100%). At last examination, best corrected visual acuity improved in five eyes and remained unchanged in three eyes. Vision impairment and pain scores improved in all patients (p < .05). This study demonstrates that transplantation of autologous limbal epithelial stem cells cultured on HAM without the use of non-human animal cells or products is a safe and effective method of reconstructing the corneal surface and restoring useful vision in patients with unilateral total LSCD.

Stem cells for ischemic brain injury: A critical review

No effective therapy is currently available to promote recovery following ischemic stroke. Stem cells have been proposed as a potential source of new cells to replace those lost due to central nervous system injury, as well as a source of trophic molecules to minimize damage and promote recovery. We undertook a detailed review of data from recent basic science and preclinical studies to investigate the potential application of endogenous and exogenous stem cell therapies for treatment of cerebral ischemia. To date, spontaneous endogenous neurogenesis has been observed in response to ischemic injury, and can be enhanced via infusion of appropriate cytokines. Exogenous stem cells from multiple sources can generate neural cells that survive and form synaptic connections after transplantation in the stroke-injured brain. Stem cells from multiple sources cells also exhibit neuroprotective properties that may ameliorate stroke deficits. In many cases, functional benefits observed are likely independent of neural differentiation, although the exact mechanisms remain poorly understood. Future studies of neuroregeneration will require the demonstration of function in endogenously born neurons following focal ischemia. Further, methods are currently lacking to demonstrate definitively the therapeutic effect of newly introduced neural cells. Increased plasticity following stroke may facilitate the functional integration of new neurons, but the loss of appropriate guidance cues and supporting architecture in the infarct cavity will likely impede the restoration of lost circuitry. Thus careful investigation of the mechanisms underlying trophic benefits will be essential. Evidence to date suggests that continued development of stem cell therapies may ultimately lead to viable treatment options for ischemic brain injury.

Introduction to Cellular Therapy

Cell therapy represents a new frontier in the development of therapeutics for stroke. Aside from physical rehabilitation, few options exist to enhance recovery from stroke. Prior studies in the 1990s provided precedence for considering a cellular approach to treat neurological disorders with the pioneering work on transplantation in Parkinson disease. These trials furnished preliminary evidence for a modest benefit in young patients with a neurodegenerative disorder who underwent neural transplantation. From those initial studies, pilot work emerged on the application of cellular replacement in Huntington disease and other neurological disorders. In an entirely different area of medicine, stem cell transplantation in oncology provided support for the idea that stem cells could be administered intravenously for a range of disorders including stroke. Over the past decade, investigators accordingly began showing that intravenously injected stem cells from the bone marrow and umbilical cord could promote recovery in animal stroke models. Thus began a new area of investigation in which adult stem cells from other sources, rather than the brain, could be tested for therapeutic applications in stroke. As transplantation studies have been growing, it has also now clearly been established that the adult brain undergoes neurogenesis. Elegant work from Lindvall and Parent and others have shown that …

Bone Marrow Stem Cell Therapy for Myocardial Angiogenesis

Despite the recent advances in medical therapy and coronary revascularization procedures, coronary artery disease (CAD) remains the major cause of morbidity and mortality in the developing countries. In patients with severe CAD, persistent myocardial ischemia in hibernated myocardium resulted in progressive loss of cardiomyocytes with development of heart failure. As a result, therapeutic approaches to enhance neovascularization are being underwent intensive investigation. Recent experimental studies have demonstrated adult bone marrow (BM) can induce neovascularization in ischemic myocardium can improve heart function. These findings have prompted the development of different cellular transplantation approaches for heart diseases refractory to conventional therapy after myocardial infarction. Although the initial pilot clinical trials have shown potential clinical benefit of BM therapy for therapeutic angiogenesis, the long-term safety, the optimal timing and treatment strategy remains unclear. Furthermore, in order to acquire more optimized quality and quantity of BM derived stem cell for myocardial regeneration, several issues remain to be addressed, such as the development of a more efficient method of stem cells identification, purification and expansion. Emerging, rationally designed, randomized clinical trials are required to assess the clinical implication of BM derived stem cells therapy in treatment of CAD.

Stem cells for repair of the heart

Stem cell therapy for treatment of cardiac disease has shown therapeutic potential. A number of stem and progenitor populations have been identified for potential use in cardiac repair. Each possesses a unique potency that justifies consideration for use. Autologous, unfractionated bone marrow cells or skeletal myoblasts were used in early clinical trails to evaluate reparative effects on recent or record infarcts. In each case, evidence of limited improvement in cardiac function was obtained. Myoblast grafts were unexpectedly correlated with arrhythmias, thereby identifying a safety issue. The small number of patients and the lack of randomized control groups preclude conclusions regarding efficacy. Randomized controlled, intermediate-sized, double-blind clinical trials must be undertaken to this end. Cellular therapy may be useful in the treatment of cardiac disease in adults. Appropriate adaptations to meet unique requirements for treatment of pediatric cardiovascular disease may be required. Bone marrow and skeletal myoblasts do not promote true tissue regeneration in spite of observed functional improvement. Trials using cells possessing true potential for (trans)differentiation may elucidate the potential and value of this therapy as a reparative modality. Development of optimal strategies for targeted delivery consistent with pathobiology is of exception clinical relevance.

Left ventricular assist devices: evolving devices and indications for use in ischemic heart disease

The mortality with end-stage heart failure is extremely high, especially when patients become refractory to conventional medical therapy and require frequent hospitalization. Ischemic heart disease remains the primary cause of advanced heart failure. Mechanical pumps or devices have been developed called ventricular assist devices and are being used to support an increasing number of patients with refractory heart failure. The use of ventricular assist devices has evolved from initially only support of patients unable to be weaned from a heart-lung machine after cardiac surgery to use now as a bridge to a heart transplant, including patients with acute myocardial infarction and shock and severe pulmonary hypertension. More recently, they have been proven as a definitive alternative for patients not eligible for heart transplantation. There are new devices being examined in clinical trials, including a change from pusher-plate to devices with axial flow technology that are much smaller and easier to implant. Outcomes with their use are improving rapidly as the devices become more reliable and more is learned about the importance of candidate selection. This review describes current indications for the use of these devices, the types of pumps now available, criteria for initiating ventricular assist device support, complications of their use, and new applications such as a platform for stem cell therapy for treatment of end-stage heart failure.

486: Stem Cell Therapy in Treatment of Urinary Incontinence: First Clinical Results

486: Stem Cell Therapy in Treatment of Urinary Incontinence: First Clinical Results

184 Stem cell therapy in treatment of urinary incontinence: First clinical results

184 Stem cell therapy in treatment of urinary incontinence: First clinical results

Autologous stem cell therapy for treatment of severe inflammatory autoimmune diseases

Autologous stem cell therapy for treatment of severe inflammatory autoimmune diseases