Allogeneic Human Mesenchymal Stem Cells in Patients With Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER): A Phase I Safety Clinical Trial.

Background: Despite Food and Drug Administration approval of 2 new drugs for idiopathic pulmonary fibrosis (IPF), curative therapies remain elusive and mortality remains high. Preclinical and clinical data support the safety of human mesenchymal stem cells as a potential novel therapy for this fatal condition. The Allogeneic Human Cells (hMSC) in patients with Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER) trial was the first study designed to evaluate the safety of a single infusion of bone marrow-derived mesenchymal stem cells in patients with idiopathic pulmonary fibrosis.

Fluorescence in situ hybridization using an old world monkey Y chromosome specific probe combined with immunofluorescence staining on rhesus monkey tissues.

To date, there is no commercially available Y chromosome probe that can be used for fluorescence in situ hybridization (FISH) for the male rhesus monkey. We have recently generated a probe for FISH with high specificity to the short arm of the rhesus monkey Y chromosome. In this study, we further describe a method that keeps the integrity of tissue-specific antigenic structures for immunofluorescence staining subsequent to FISH on paraffin-embedded rhesus monkey tissues.

Potential of mesenchymal stem cells in gene therapy approaches for inherited and acquired diseases.

The intriguing biology of stem cells and their vast clinical potential is emerging rapidly for gene therapy. Bone marrow stem cells, including the pluripotent haematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs) and possibly the multipotent adherent progenitor cells (MAPCs), are being considered as potential targets for cell and gene therapy-based approaches against a variety of different diseases. The MSCs from bone marrow are a promising target population as they are capable of differentiating along multiple lineages and, at least in vitro, have significant expansion capability.

Signal transduction pathways involved in the lineage-differentiation of NSCs: can the knowledge gained from blood be used in the brain?

Neural stem cells (NSC) are capable of differentiating toward neuronal, astrocytic, oligodendrocytic and glial lineages, depending on their spatial location within the central nervous system (CNS). Although, a lot of knowledge has been gained in the understanding of differentiation-specific signaling in hematopoietic (HSC) and mesenchymal (MSC) counterparts, the molecular mechanisms underlying lineage commitment in NSCs are just beginning to be understood. Furthermore, it is not well comprehended as to how the specification of one cell lineage can result in the suppression of parallel pathways in the NSCs.

Transduction of bone-marrow-derived mesenchymal stem cells by using lentivirus vectors pseudotyped with modified RD114 envelope glycoproteins.

Bone-marrow-derived mesenchymal stem cells (MSCs) have attracted considerable attention as tools for the systemic delivery of therapeutic proteins in vivo, and the ability to efficiently transfer genes of interest into such cells would create a number of therapeutic opportunities. We have designed and tested a series of human immunodeficiency virus type 1 (HIV-1)-based vectors and vectors based on the oncogenic murine stem cell virus to deliver and express transgenes in human MSCs. These vectors were pseudotyped with either the vesicular stomatitis virus G (VSV-G) glycoprotein (GP) or the feline endogenous virus RD114 envelope GP.

Neuronal stem cells biology and plasticity.

Recent studies have suggested that stem cells are able to cross primordial tissue barriers. Their ability to respond to unrelated microenvironmental signals strongly suggest that they have greater potential than previously imagined especially for their future clinical use for the regeneration of tissues or even perhaps organ systems. In particular there is an intriguing reciprocal relationship between the hematopoietic and neuronal stem cell systems.

Imatinib (ST1571) provides only limited selectivity for CML cells and treatment might be complicated by silent BCR-ABL genes.

Very promising results have been obtained in clinical trials on chronic-phase chronic myeloid leukemia (CP-CML) patients treated with imatinib mesylate (IM; Gleevecr, STI571), a BCR-ABL tyrosine kinase inhibitor. However, we found that IM caused considerable inhibition of normal hematopoietic progenitor cells upon treating control bone marrow (BM) cultures. In vitro IM treatment gave a decrease in the yield and size of colonies from BM of untreated CP-CML patients that was only two to three times that from the normal samples.

Suppression of clonogenic potential of human bone marrow mesenchymal stem cells by HIV type 1: putative role of HIV type 1 tat protein and inflammatory cytokines.

Bone marrow abnormalities are frequently observed in HIV-1-infected individuals. Infection of marrow mesenchymal stem cells (MSCs) may abrogate their growth properties and hematopoietic supportive functions. To delineate the cell type infected, and factors responsible for the deleterious effects, human bone marrow cells were exposed to HIV-1 in vitro.

Lentiviral vectors for sustained transgene expression in human bone marrow-derived stromal cells.

Bone marrow-derived mesenchymal stromal cells (MSCs) have attracted attention as potential platforms for the systemic delivery of therapeutic proteins in vivo following gene transfer using oncogenic retroviruses. However, the major limitations of this strategy include low levels of gene transfer and a general lack of long-term transgene expression. We have investigated the expression of several transgenes in MSCs following HIV-1 lentiviral vector-mediated gene transfer.

Blood vascular system of the sea cucumber, Stichopus moebii.

Stichopus moebii, a sea cucumber, has a closed circulatory system which is unique in its degree of development for the phylum Echinodermata. The gross anatomy, histology and fine structure of the system were studied. Blood vessels consist of a coelomic surface of ciliated epithelium, a layer of muscle and nerve cells, followed by connective tissue and luminal lining of endothelium.