Effects Of Stem Cell Treatment Research Articles

Cortical Bone–Derived Stem Cells

Acute myocardial infarction (MI) remains a significant cause of mortality and morbidity worldwide, despite steady advances in our understanding and treatment of coronary heart disease.1 After MI, lost myocardium is replaced with scar tissue, leading to left ventricular (LV) remodeling and ultimately culminating with ischemic cardiomyopathy and congestive heart failure. We now know that the adult heart is not a postmitotic organ lacking capacity for self-renewal after injury. This paradigm shift occurred after identification of stem cell niches in the adult heart and isolation of cardiac progenitor cells, including c-kit+ cardiac stem cells (CSCs), side population cells, and cardiospheres.2–7 However, the endogenous proliferation of cardiac progenitor cells after MI is inadequate for full replacement of the large number of depleted cells.8 To overcome this problem, extensive efforts have been made in developing cell-based therapies to promote tissue repair by introduction of exogenous cells, such as bone marrow–derived mononuclear cells (BM-MNCs), bone marrow–derived mesenchymal stem cells (BM-MSCs), adipose tissue–derived mesenchymal stem cells, CD34+ stem cells, c-kit+ CSCs, and cardiosphere-derived cells, as evidenced by recent clinical trials.9–16 Article, see p 539 For now, the BM-MNCs are the most widely used source of cells in cardiovascular regenerative therapy trials. However, despite some successful early-stage clinical trials, several recent studies involving the use of BM-MNCs have not been overwhelmingly positive. For example, in the placebo-controlled Transplantation in Myocardial Infarction Evaluation (TIME) trial in which investigators assessed whether differential timing of BM-MNCs delivery affected LV ejection fraction (LVEF) after acute MI (3–7 days), no significant differences between the BM-MNCs and placebo groups were observed for either primary or secondary end points.17 In fact, the TIME trial was the third study in a series of studies (Late-TIME,18 Effectiveness of Stem Cell Treatment for …

Effects of Hematopoietic Autologous Stem Cell Transplantation to the Chronically Injured Human Spinal Cord Evaluated by Motor and Somatosensory Evoked Potentials Methods

International standards for stem cell treatment of neurological disorders have not yet been established. In particular, specific quantitative methods have not yet been adopted to assess the effectiveness of stem cell treatment. The aim of this study is to evaluate the functional changes detectable by conventional neurophysiologic methods in an injured spinal cord during stem cell therapy. Twenty adult patients with chronic spinal cord injury at C4-C8 level were examined by somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) methods, the first time prior to the treatment and then regularly during its course (1-4 years). The treatment consisted of repeated intrathecal transplantations of autologous hematopoietic stem cells. After at least 1 year of treatment, four effects were detected: 1) restoration of the initially absent short-latency SEP (three patients); 2. N20P23 interpeak amplitude increase in SEP elicited by median nerve stimulation (four patients); 3) P38 latency reduction in SEP elicited by tibial nerve stimulation (two patients); 4) appearance of MEP (three patients). The nonidentical effects of stem cell transplantation in different patients presumably reflect the variety of the regeneration processes in different pathways of the spinal cord, depending on the extent and nature of lesion of the spinal cord pathways in different patients. The local effects of stem cell treatment at the cervical level were evaluated by median SEP and wrist muscle MEP demonstrate the ability of stem cells to spread within the spinal cord at least from lumbar to the cervical level, home there, and participate in the neurorestoration processes.

Treatment with Autologous Bone Marrow Mononuclear Cells in Patients with Non Reconstructable Critical Lower Limb Ischaemia

Background and Aims: Treatment with autologous, bone marrow mononuclear stem cells has shown effects in patients with chronic limb ischaemia. The aim of the study was to test the potential effect of stem cell treatment in a strict defined group of patients with non reconstructable critical limb ischaemia (CLI). Material: Twenty patients with non recontructable CLI of the lower extremities, who received medical treatment in the form of prostavasine. Methods: Bone marrow cells were harvested from the patient’s iliac crest and, after separation, injected into the calf muscles of the affected leg. Outcome was evaluated by digital subtraction angiography (DSA), visual analogue scale (VAO) one patient was amputated two months after cell injection. Two patients reported relief of pain after four months. Conclusion: This method seems to be a safe option for treating patients with non reconstructable CLI.

Bone marrow stromal cells isolated from the infarcted region of the postischemic brain secrete neuroprotective and angiogenic factors

Although the therapeutic potential of bone marrow stromal cells (BMSC) has been demonstrated in stroke, there is limited information about the neuroprotective factors secreted by BMSC in the infarcted brain. The objective of this study was to compare the expression of genes for extracellular (EXC) factors produced by BMSC infiltrating brain tissue vs their naïve counterparts. Ischemic stroke was induced in C57BL/6 mice by middle cerebral artery occlusion for 1 h, followed by 24 h reperfusion. BMSC were isolated from H‐2Kb‐tsA58 mice (cells can grow at 33°C), and were administered (i.v.) at 24 h of reperfusion. Infarcted hemispheres were cultured at 33°C for BMSC isolation. Microarray analysis and RT‐PCR were performed to compare gene expression patterns between the BMSC populations in 9 mice. Z‐scoring revealed a robust change in the extracellular region of analyzed cells. Pair‐wise analysis detected 163 extracellular factor genes that were upregulated (≥ 2 fold, P<0.05) between naïve and infiltrated BMSC. Fibroblast growth factors, bone morphogenetic protein, angiopoietins, neural and vascular growth factors were among the expressed genes detected. Our findings indicate that extracellular factors secreted by BMSC infiltrating the postischemic brain may explain the beneficial therapeutic effects of stem cell treatment and reveal potential therapeutic agents for treatment of ischemic stroke. (HL26411)

Treatment with Autologous Bone Marrow Mononuclear Cells in Patients with Critical Lower Limb Ischaemia. A Pilot Study

Treatment with autologous, bone marrow mononuclear stem cells has shown effects in patients with chronic limb ischaemia in one randomized clinical study. The aim of the study was to test the potential effect of stem cell treatment in a strict defined group of patients with stable critical limb ischaemia (CLI). A prospective, combined-centre pilot study. Eight patients with CLI of the lower extremities, and without any other treatment options. Bone marrow cells were harvested from the patient's iliac crest and, after separation, injected into the calf muscles of the affected leg. Outcome was evaluated by digital subtraction angiography (DSA), visual analogue scale (VAS) and several non-invasive circulatory physiological tests. There were no complications from the procedures. Two patients were amputated two months after cell injection. Five patients reported pain relief after four months. Five patients could be evaluated at eight months. According to VAS and physiological tests, they were all either stable or showed improvement. This method seems to be a safe option for treating patients with CLI. Inclusion of patients took a long time, mainly because many patients with CLI are offered endovascular treatment in our institution. While symptomatic improvement was found in individual patients, larger trials are required to investigate efficacy. This will probably require multi-centre participation.

Healing time, long-term result and effects of stem cell treatment in acute tympanic membrane perforation

The incidence of otitis media in children between the age of 2 and 6 years is well documented. Repeated attacks may cause acute and chronic perforations. The surgical treatment for repairing chronic perforation is quite uncomfortable for the patients of this age group because of the invasiveness of this treatment. The aim of this study was to determine the long-term influence of embryonic stem cells on acute perforations and the effect of gelatin as a vehicle for applied stem cells. The possibility of teratogenic effects of the stem cells was also observed. Bilateral laser myringotomy was performed in 17 adult Sprague-Dawley rats, divided into two groups. Gelatin, a substance suitable as vehicle for bioactive material was used bilaterally around the perforation in group A, to serve as a scaffold for repairing tissue. The stem cells were used in the right tympanic membrane perforation leaving the left tympanic membrane as a control. The animals in group B received the same treatment except for the use of gelatin and in addition received an immuno-suppressive agent. After half a year of observation the mechanical stiffness of the tympanic membrane was measured by moiré interferometry for group B and the morphological study was performed by light microscopy for both groups A and B and electron microscopy for group A. Stem cell treated ears did not show any enhanced healing of the perforation although a marked thickening of the lamina propria was observed compared with control group. After half a year the strength and the stiffness of the tympanic membrane was almost the same for both treated and untreated ears. No evidence of teratoma was found after half a year. This study suggests that the stem cells stimulate the proliferation of connective tissue and fibers in the lamina propria, possibly mediated by secreted substances, although the stiffness properties do not seem to be altered. The use of gelatin does not seem to enhance the healing process of the tympanic membrane perforation.