Trophic Factors in the Therapeutic Challenge Against ALS: Current Research Directions

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, which up to date remains incurable. Multiple experimental approaches toward finding an effective way of reducing ALS progression and improving patients’ condition have been proposed but none of them brought significant desired effects. In recent years, studies focused on stem cells (SCs) have proven that not only cells themselves but also trophic factors, which they secrete, may cause positive effects on neural tissue environment. Crucial issues that have to be considered in any study implementing SC’s secreted trophic factors are administration route and type of administered cells. Furthermore, the understanding of trophic factor function, secretion manner, and their potential influence on damaged cells may be immensely beneficial. This chapter focuses on recent studies exploiting trophic factors to improve ALS patients and animal ALS models’ condition

Nieembrionalne komórki macierzyste a regeneracja układu nerwowego

Strategie lecznicze oparte na wykorzystaniu komórek macierzystych stwarzają nadzieję na opracowanie efektywnych metod terapeutycznych dla wielu, do tej pory nieuleczalnych, schorzeń. Nowoczesna dziedzina nauk medycznych, jaką jest medycyna regeneracyjna, rozwija się w kierunku wykorzystywania komórek macierzystych w leczeniu między innymi udaru niedokrwiennego mózgu, uszkodzeń rdzenia kręgowego czy chorób neurodegeneracyjnych. Duże nadzieje wiąże się z wykorzystaniem komórek pochodzących z tkanek dorosłych osobników. Opisana ostatnio populacja komórek macierzystych (VSEL SC, very small embryonic-like stem cells), wyizolowana między innymi z ludzkiej krwi pępowinowej, posiada wiele cech charakterystycznych dla wczesnych komórek embrionalnych. Uważa się, że komórki te mogą stać się źródłem najwcześniejszych rozwojowo komórek pluripotencjalnych wykorzystywanych w medycynie regeneracyjnej. Polski Przegląd Neurologiczny 2008; 4 (1): 15-1

Bone marrow morphology during haematopoietic stem cell mobilisation with cyclophosphamide in mice

The aim of the study was to examine the morphology of the bone marrow of mice after stimulation with cyclophosphamide (Cy). The experimental mice were given a single intraperitoneal injection with 250 mg/kg bw cyclophosphamide. After 2, 4 and 6 days of experiment the femurs were obtained for morphological study. On the 2nd day after the mobilisation of the mice with Cy destruction of the bone marrow was observed with a decrease in the haematopoietic compartment and an increase in the area occupied by sinusoids filled with erythrocytes. Erythrocytes were located among the haematopoietic cells, which indicated that the endothelial barrier had been disrupted. On the 4th day after treating the mice with Cy, repair processes in the bone marrow were conducted, including macrophages. The cells filled with haemosiderin migrated from the extravascular compartment of the bone marrow into the lumen of the sinusoids. There were proliferating cells among the haematopoietic cells. On the 6th day the morphology of the bone marrow was similar to the morphology of that in the control mice. However, more haematopoietic cells were visible compared to the control bone marrow. The presence of an increased number of leucocytes in the sinusoid lumen in comparison with the control suggested that at that time the migration of haematopoietic cells from the bone marrow had been initiated

Risk Factors and Symptoms of Meibomian Gland Loss in a Healthy Population

Purpose. The aim of this study was to investigate the relationships between MGL and ocular symptoms, several systemic conditions, and key markers of ocular surface health. Methods. We included into the study 91 healthy volunteers between the ages of 20 and 77 years. We analyzed meibomian gland morphology, function, and lid margin alterations. We correlated our findings with self-reported ocular symptoms, systemic medical history, lifestyle factors, and tear film abnormalities. Results. We observed that a high ocular surface disease index, a history of either chalazion or hordeolum, experience of puffy eyelids upon waking, and foreign body sensation all appeared to be predictors of an abnormal meiboscore after adjusting for age and sex (p=0.0007; p=0.001; p=0.02; p=0.001, resp.). Multivariate logistic regression model including age and sex showed that there were three independent predictors of abnormal meiboscore: older age (OR = 1.03, 95% CI = 1.01–1.04 per year, p=0.006), postmenopausal hormone therapy (OR = 4.98, 95% CI = 1.52–16.30, p=0.007), and the use of antiallergy drugs (OR = 5.85, 95% CI = 2.18–15.72, p=0.0004). Conclusion. Our findings extend current knowledge on the pathophysiology of MGL

Bone marrow morphology during haematopoietic stem cell mobilization with G-CSF in mice

The aim of the work was to examine the morphology of the bone marrow of mice during stimulation with G-CSF. Experimental Balb C mice were daily injected subcutaneously with 250 μg/kg b.w. G-CSF (Neupogen). After 2, 4 and 6 days of the experiment femurs were obtained for morphological study. On day 2 of the mobilization the amount of haematopoietic cells in the bone marrow increased and dilatation of the sinusoids was observed. Only single leukocytes were observed in the lumen of the vessels. There were numerous leukocytes in the lumen of the sinusoids on day 4 of the mobilization. The morphology of the bone marrow on day 6 was similar to that of the control. Mobilization of mice with G-CSF resulted in migration of haematopoietic cells from the bone marrow and the process is most pronounced on day 4

Komórki macierzyste w klinicznych badaniach kardiologicznych

Stem cell-based therapy is a novel therapeutic strategy introduced into cardiology, although there are not any established standards within the stem/progenitor cell type employed, their preparation, rout of administration as well as methods controlling the pathophysiological and clinical parameters after the cell application. The aim of the present work was a complex metaanalysis of the clinical trials carried out in this field. Over 1000 patients with myocardial infarction as well as circulatory failure have been treated with stem cell-based therapy so far, but the obtained results are not concordant. Progress within cell biology and biotechnology give hopes for development of more effective therapeutic approaches. Identification and isolation of cardiac- -specific stem/progenitor cells may deliver new perspectives for such therapy in the nearest future. Kardiol Pol 2011; 69, 6: 601–60

Morphology of the bone marrow, spleen and liver during hematopoietic cell mobilization with cyclophosphamide in mice.

Cyclophosphamide (CY), the agent with cytoreductive activity, is widely exploited in cancer chemotherapy, and can be used alone or in combination with various cytokines and growth factors to stimulate the egress of hematopoietic stem/progenitor cells (HSPC) from the BM compartment. The aim of the present study was to exam the morphology and ultrastructure of the bone marrow, spleen and liver of mice injected intraperitoneally with a single dose of cyclophosphamide (200 mg/kg bw) and the localization of cells expressing markers of early hematopoietic cells in studied organs and the peripheral blood. We observed that the CY-induced morphological changes in the BM and spleen were reconstructed on day 4. of experiment, and the spleen was repopulated by HSPC on the 6th day. In this time, the highest number of c-Kit-R-positive cells was determined by flow cytometry in the peripheral blood. The results confirmed, that the egress of HSPC from the bone marrow into the peripheral blood was delayed compared to mice treated with G-CSF or GCS-F plus CY

Safety and feasibility of Lin- cells administration to ALS patients : a novel view on humoral factors and miRNA profiles

Therapeutic options for amyotrophic lateral sclerosis (ALS) are still limited. Great hopes, however, are placed in growth factors that show neuroprotective abilities (e.g., nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor (VEGF)) and in the immune modulating features, in particular, the anti-inflammatory effects. In our study we aimed to investigate whether a bone marrow-derived lineage-negative (Lin-) cells population, after autologous application into cerebrospinal fluid (CSF), is able to produce noticeable concentrations of trophic factors and inflammatory-related proteins and thus influence the clinical course of ALS. To our knowledge, the evaluation of Lin- cells transplantation for ALS treatment has not been previously reported. Early hematopoietic Lin- cells were isolated from twelve ALS patients’ bone marrow, and later, the suspension of cells was administered into the subarachnoid space by lumbar puncture. Concentrations of selected proteins in the CSF and plasma were quantified by multiplex fluorescent bead-based immunoassays at different timepoints post-transplantation. We also chose microRNAs (miRNAs) related to muscle biology (miRNA-1, miRNA-133a, and miRNA-206) and angiogenesis and inflammation (miRNA-155 and miRNA-378) and tested, for the first time, their expression profiles in the CSF and plasma of ALS patients after Lin- cells transplantation. The injection of bone marrow cells resulted in decreased concentration of selected inflammatory proteins (C3) after Lin- cells injection, particularly in patients who had a better clinical outcome. Moreover, several analyzed miRNAs have changed expression levels in the CSF and plasma of ALS patients subsequent to Lin- cells administration. Interestingly, the expression of miR-206 increased in ALS patients, while miR-378 decreased both in the CSF and plasma one month after the cells’ injection. We propose that autologous lineage-negative early hematopoietic cells injected intrathecally may be a safe and feasible source of material for transplantations to the central nervous system (CNS) environment aimed at anti-inflammatory support provision for ALS adjuvant treatment strategies. Further research is needed to evaluate whether the observed effects could significantly influence the ALS progression