This study demonstrated the safety and short-term efficacy of autologous bone marrow-derived mesenchymal stem cell injection in liver cell failure. Further study is necessary to standardize the cell dose, determine the life span of the injected cells, and detect the appearance of long-term complications.
Autologus MSCs may have side effects and may be contraindicated in patients with a history of myelitis. Their utility in treating chronic traumatic SCI needs further study in pre-clinical models and in randomized controlled trials before they should be offered to patients.
Spinal cord injuries (SCI) cause sensory loss and motor paralysis. They are normally treated with physical therapy, but most patients fail to recover due to limited neural regeneration. Here we describe a strategy in which treatment with autologous adherent bone marrow cells is combined with physical therapy to improve motor and sensory functions in early stage chronic SCI patients. In a phase I/II controlled single-blind clinical trial (clinicaltrials.gov identifier: NCT00816803), 70 chronic cervical and thoracic SCI patients with injury durations of at least 12 months were treated with either intrathecal injection(s) of autologous adherent bone marrow cells combined with physical therapy or with physical therapy alone. Patients were evaluated with clinical and neurological examinations using the American Spinal Injury Association (ASIA) Impairment Scale (AIS), electrophysiological somatosensory-evoked potential, magnetic resonance imaging (MRI), and functional independence measurements. Chronic cervical and thoracic SCI patients (15 AIS A and 35 AIS B) treated with autologous adherent bone marrow cells combined with physical therapy showed functional improvements over patients in the control group (10 AIS A and 10 AIS B) treated with physical therapy alone, and there were no long-term cell therapy-related side effects. At 18 months posttreatment, 23 of the 50 cell therapy-treated cases (46%) showed sustained functional improvement. Compared to those patients with cervical injuries, a higher rate of functional improvement was achieved in thoracic SCI patients with shorter durations of injury and smaller cord lesions. Therefore, when combined with physical therapy, autologous adherent bone marrow cell therapy appears to be a safe and promising therapy for patients with chronic SCI of traumatic origin. Randomized controlled multicenter trials are warranted.
IntroductionDoxorubicin (DOX) is a well-known anticancer drug. However its clinical use has been limited due to cardiotoxic effects. One of the major concerns with DOX therapy is its toxicity in patients who are frail, particularly diabetics. Several studies suggest that mesenchymal stem cells (MSCs) have the potential to restore cardiac function after DOX-induced injury. However, limited data are available on the effects of MSC therapy on DOX-induced cardiac dysfunction in diabetics. Our objective was to test the efficacy of bone marrow-derived (BM-MSCs) and adipose-derived MSCs (AT-MSCs) from age-matched humans in a non-immune compromised rat model.MethodsDiabetes mellitus was induced in rats by streptozotocin injection (STZ, 65 mg/kg b.w, i.p.). Diabetic rats were treated with DOX (doxorubicin hydrochloride, 2.5 mg/kg b.w, i.p) 3 times/wk for 2 weeks (DOX group); or with DOX+ GFP labelled BM-MSCs (2x106cells, i.v.) or with DOX + GFP labelled AT-MSCs (2x106cells, i.v.). Echocardiography and Langendorff perfusion analyses were carried out to determine the heart function. Immunostaining and western blot analysis of the heart tissue was carried out for CD31 and to assess inflammation and fibrosis. Statistical analysis was carried out using SPSS and data are expressed as mean ± SD.ResultsGlucose levels in the STZ treated groups were significantly greater than control group. After 4 weeks of intravenous injection, the presence of injected MSCs in the heart was confirmed through fluorescent microscopy and real time PCR for ALU transcripts. Both BM-MSCs and AT-MSCs injection prevented DOX-induced deterioration of %FS, LVDP, dp/dt max and rate pressure product. Staining for CD31 showed a significant increase in the number of capillaries in BM-MSCs and AT-MSCs treated animals in comparison to DOX treated group. Assessment of the inflammation and fibrosis revealed a marked reduction in the DOX-induced increase in immune cell infiltration, collagen deposition and αSMA in the BM-MSCs and AT-MSCs groups.ConclusionsIn conclusion BM-MSCs and AT-MSCs were equally effective in mitigating DOX-induced cardiac damage by promoting angiogenesis, decreasing the infiltration of immune cells and collagen deposition.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0142-x) contains supplementary material, which is available to authorized users.
Introduction:Real-time reverse-transcriptase polymerase chain reaction (RT-PCR) assays were established to detect severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). However, due to the high rate of false negative results, additional tests as computed tomography (CT) scans of the chest and blood chemistry are required to properly diagnose COVID-19 infection. Abnormal morphological changes of peripheral blood cells as granulocytic dysmorphism and abnormal reactive lymphocytes have been described in some cases. The aim of the present study was to investigate the morphological changes affecting all peripheral blood cells of COVID-19 patients, in order to find any specific abnormalities that could help in the early diagnosis and/ or prognosis.Methods: Peripheral blood smears of 113 COVID-19 patients and 50 non-COVID-19 controls were examined for morphological changes in the period between October 2020 and January 2021 (second wave). We set a score value in which every morphological abnormality was given one point in each examined blood smear. Score, neurophil/lymphocyte (N/L) ratio, and blood chemistry were compared to the severity and outcome of the disease.Results: Significant morphological changes were found when compared to control blood smears. Various abnormalities as pyknotic cells, broken cells, pseudo Pelger-Huët, abnormal lymphocytes, abnormal monocytes, and leukoerythroblastic reaction were found. Cases with higher scores had unfavorable outcomes (p = .005). High interleukin-6 (IL-6) levels were correlated to pyknotic cells (p = .003).
Conclusion:The blood picture of COVID-19 patients revealed various morphological changes that are not detected with the same frequency and variability in other viral infections. The prominent morphological changes can be predictive of an undesirable outcome of the disease.
Patients with dystrophic epidermolysis bullosa (DEB) have mutations in type VII collagen gene. Type VII collagen is synthesized by keratinocytes and fibroblasts. Based on the ability of bone marrow non-hematopoeitic stem cells (NHBMSC) to develop into fibroblasts, we decided to investigate the use of NHBMSC in the treatment of recessive DEB (RDEB). This study included fourteen patients with RDEB; the first seven of them were given cyclosporine after the infusion of NHBMSC. As cyclosporine has been used for the treatment of RDEB we decided not to use cyclosporine for the second group of seven patients. Skin biopsies from the lesions were studied by electron microscopy before and after treatment. The number of new blisters decreased significantly after treatment in both groups (p = 0.003 and 0.004 respectively) and the rate of healing of new blisters became significantly faster after treatment in both groups (p < 0.001) with no significant difference between the two groups. Electron microscopic examination revealed increased number of anchoring fibrils after treatment in both groups. No major side effects were reported during the 1-year follow-up period. Our findings highlight the efficacy as well as the safety of NHBMSC in the treatment of RDEB.
In response to increased research being performed in developing countries, many research ethics committees (RECs) have been established, but the quality of their ethics review systems remains unknown. Evaluating the performance of an REC remains a challenging task. Absent an accreditation process, a self-assessment mechanism would provide RECs a way to review their policies and processes against recognized international standards. We describe a self-assessment tool that was developed and reviewed by REC members and researchers from the Middle East. This tool reflects pragmatic aspects of human subjects protection, is based on international standards, is straightforward in its completion, and its items are relevant to the administrative processes that exist in many RECs in the developing world.
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