Efficacy and Safety of Human Retinal Progenitor Cells.

Purpose: We assessed the long-term efficacy and safety of human retinal progenitor cells (hRPC) using established rodent models.

Methods: Efficacy of hRPC was tested initially in Royal College of Surgeons (RCS) dystrophic rats immunosuppressed with cyclosporine/dexamethasone. Due to adverse effects of dexamethasone, this drug was omitted from a subsequent dose-ranging study, where different hRPC doses were tested for their ability to preserve visual function (measured by optokinetic head tracking) and retinal structure in RCS rats at 3 to 6 months after grafting.

Multipotent human stromal cells isolated from cord blood, term placenta and adult bone marrow show distinct differences in gene expression pattern.

Multipotent mesenchymal stromal cells derived from human placenta (pMSCs), and unrestricted somatic stem cells (USSCs) derived from cord blood share many properties with human bone marrow-derived mesenchymal stromal cells (bmMSCs) and are currently in clinical trials for a wide range of clinical settings. Here we present gene expression profiles of human cord blood-derived unrestricted somatic stem cells (USSCs), human placental-derived mesenchymal stem cells (hpMSCs), and human bone marrow-derived mesenchymal stromal cells (bmMSCs), all derived from four different donors. The microarray data are available on the ArrayExpress database (www.

Engraftment Outcomes after HPC Co-Culture with Mesenchymal Stromal Cells and Osteoblasts.

Haematopoietic stem cell (HSC) transplantation is an established cell-based therapy for a number of haematological diseases. To enhance this therapy, there is considerable interest in expanding HSCs in artificial niches prior to transplantation. This study compared murine HSC expansion supported through co-culture on monolayers of either undifferentiated mesenchymal stromal cells (MSCs) or osteoblasts.

Comprehensive transcriptome and immunophenotype analysis of renal and cardiac MSC-like populations supports strong congruence with bone marrow MSC despite maintenance of distinct identities.

Cells resembling bone marrow mesenchymal stem cells (MSC) have been isolated from many organs but their functional relationships have not been thoroughly examined. Here we compared the immunophenotype, gene expression, multipotency and immunosuppressive potential of MSC-like colony-forming cells from adult murine bone marrow (bmMSC), kidney (kCFU-F) and heart (cCFU-F), cultured under uniform conditions. All populations showed classic MSC morphology and in vitro mesodermal multipotency.

Micromarrows--three-dimensional coculture of hematopoietic stem cells and mesenchymal stromal cells.

Hematopoietic stem cell (HSC) transplant is a well established curative therapy for some hematological malignancies. However, achieving adequate supply of HSC from some donor tissues can limit both its application and ultimate efficacy. The theory that this limitation could be overcome by expanding the HSC population before transplantation has motivated numerous laboratories to develop ex vivo expansion processes.

Development of myocardial constructs using modulus-matched acrylated polypropylene glycol triol substrate and different nonmyocyte cell populations.

Tissue engineering approaches are currently being investigated for the restoration of myocardial function in heart failure patients, most commonly by combining cells with a substrate to form myocardial-like constructs (MCs). The final properties of these constructs are dependant on the characteristics of both the substrate and the cells used for fabrication. To create a construct with the appropriate mechanical properties required for any future therapeutic, we tailored an acrylated polypropylene glycol triol (aPPGT) substrate to the elastic modulus of heart tissue and then investigated the fabrication of MCs.

Manufacture of clinical grade human placenta-derived multipotent mesenchymal stromal cells.

Clinical grade human mesenchymal stem cells (MSC) are manufactured and used in clinical trials for a range of regenerative and inflammatory diseases. Human MSC have now been derived from tissues other than bone marrow, such as placenta, as described in this laboratory protocol. It provides instructions for clinical grade MSC manufacturing according to the Code of Good Manufacturing Practice (cGMP) principles and according to policies and procedures of our internal Quality Management System (QMS), which is based on the International Organization for Standardization (ISO) standard requirements.

A synthetic elastomer based on acrylated polypropylene glycol triol with tunable modulus for tissue engineering applications.

As strategies for manipulating cellular behaviour in vitro and in vivo become more sophisticated, synthetic biomaterial substrates capable of reproducing critical biochemical and biophysical properties (or cues) of tissue micro-environments will be required. Cytoskeletal tension has been shown to be highly deterministic of cell fate decisions, yet few synthetic biomaterials are capable of modulating cytoskeletal tension of adhered cells through variations in stiffness, at least in the ranges applicable to tissue properties (e.g.

A defined medium and substrate for expansion of human mesenchymal stromal cell progenitors that enriches for osteo- and chondrogenic precursors.

Human mesenchymal stromal cells (hMSCs) have generated significant interest due to their potential use in clinical applications. hMSCs are present at low frequency in vivo, but after isolation can be expanded considerably, generating clinically useful numbers of cells. In this study, we demonstrate the use of a defined embryonic stem cell expansion medium, mTeSR (Stem Cell Technologies), for the expansion of bone-marrow-derived hMSCs.

Molecular mechanisms involved in mesenchymal stem cell migration to the site of acute myocardial infarction.

Mesenchymal stem cells or multipotent mesenchymal stromal cells (both referred to as MSC) have been shown in some studies to have a beneficial effect on myocardial recovery after infarct. Current strategies for MSC delivery to heart involve intravenous, intraarterial, and intramuscular delivery. Different routes of MSC delivery and a lack of knowledge of the mechanisms that MSC utilise to migrate in vivo has most likely led to the marked variations in results that have been found.

Cellular therapy for repair of cardiac damage after acute myocardial infarction.

Cardiovascular diseases, particularly acute myocardial infarction, are the leading causes of death worldwide. Important advances have been made in the secondary treatment for cardiovascular diseases such as heart transplantation and medical and surgical therapies. Although these therapies alleviate symptoms, and may even improve survival, none can reverse the disease process and directly repair the lasting damage.

Enhanced chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells in low oxygen environment micropellet cultures.

Chondrogenesis of mesenchymal stem cells (MSCs) is typically induced when they are condensed into a single aggregate and exposed to transforming growth factor-beta (TGF-beta). Hypoxia, like aggregation and TGF-beta delivery, may be crucial for complete chondrogenesis. However, the pellet dimensions and associated self-induced oxygen gradients of current chondrogenic methods may limit the effectiveness of in vitro differentiation and subsequent therapeutic uses.

Membrane bioreactors enhance microenvironmental conditioning and tissue development.

In membrane bioreactors the cells are isolated from the bulk medium through a semipermeable membrane. This concept, which is analogous to how the circulatory system supplies solid tissues with nutrients, allows the maintenance of cells at much higher densities than is possible in traditional cultures. The membrane-based microbioreactor described herein is easy to operate, requiring only a pipette to load and harvest cells.

Manufacturing of human placenta-derived mesenchymal stem cells for clinical trials.

Mesenchymal stem cells (MSC) are being used increasingly in clinical trials for a range of regenerative and inflammatory diseases. Bone marrow is the traditional source but is relatively inaccessible in large volume. MSC have now been derived from tissues other than bone marrow including placenta and adipose tissue.

Comparison of human placenta- and bone marrow-derived multipotent mesenchymal stem cells.

Bone marrow is the traditional source of human multipotent mesenchymal stem cells (MSCs), but placenta appears to be an alternative and more readily available source. This study comprehensively compared human placenta-derived MSC (hpMSC) and human bone marrow-derived MSC (hbmMSC) in terms of cell characteristics, optimal growth conditions and in vivo safety specifically to determine if hpMSC could represent a source of human MSC for clinical trial. MSC were isolated from human placenta (hpMSC) and human bone marrow (hbmMSC) and expanded ex vivo using good manufacturing practice-compliant reagents.

Molecular trafficking mechanisms of multipotent mesenchymal stem cells derived from human bone marrow and placenta.

We compared potential trafficking mechanisms used by human (h) multipotent mesenchymal stem cells (MSC) derived from bone marrow (bm) or placenta (p). Both hbmMSC and hpMSC expressed a broad range of cell surface adhesion molecules including beta1-integrins (CD29) and CD44. Array data showed that both hbmMSC and hpMSC expressed mRNA for the cell adhesion molecules CD54 (ICAM-1), E-cadherin, CD166 (ALCAM), CD56 (NCAM), CD106 (VCAM-1), CD49a, b, c, e and f (integrins alpha1, 2, 3, 4 and 6), integrin alpha11, CD51 (integrin alphaV), and CD29 (integrins beta1).

Spatial field shifts in ocean acoustic environmental sensitivity analysis.

This article examines the effects of spatial field shifts in ocean acoustic environmental sensitivity analysis. Acoustic sensitivity studies are typically based on comparing acoustic fields computed for a reference environmental model and for a perturbed model in which one or more parameters have been changed. The perturbation to the acoustic field due to the perturbed environment generally includes a component representing a spatial shift of the field (i.

Points to Consider in Designing Mesenchymal Stem Cell-Based Clinical Trials.

SUMMARY: Therapeutic applications of cells are likely to increase greatly in the future. Cell and cell-based gene therapy manufacturing facilities need to be purpose-designed and accredited by their national medicinal regulatory body. Production scientists need to work in close tandem with quality assurance and ethics committees to absolutely ensure the safety of new cellular products.

Therapeutic applications of mesenchymal stromal cells.

Mesenchymal stromal cells (MSC) are multipotent cells that can be derived from many different organs and tissues. They have been demonstrated to play a role in tissue repair and regeneration in both preclinical and clinical studies. They also have remarkable immunosuppressive properties.

Clonal isolation and characterization of bone marrow stromal cells from patients with osteoarthritis.

The demand for treatment strategies for damaged musculoskeletal tissue is continuously growing, especially with the increasing number of older people with degenerative diseases of the skeletal system such as osteoarthritis (OA). Because depletion of multipotent cells has been implicated in degenerative joint diseases, cell-based therapies have been proposed for tissue regeneration, especially for cartilage repair. The aim of the present study is to focus on the possibility of deriving and expanding multipotential mesenchymal stem cells (MSCs) from bone marrow samples of patients with OA by characterizing MSCs at the single cell level.

Human lymphocytes interact directly with CD47 through a novel member of the signal regulatory protein (SIRP) family.

Two closely related proteins, signal regulatory protein alpha (SIRPalpha; SHPS-1/CD172) and SIRPbeta, have been described in humans. The existence of a third SIRP protein has been suggested by cDNA sequence only. We show that this third SIRP is a separate gene that is expressed as a protein with unique characteristics from both alpha and beta genes and suggest that this gene should be termed SIRPgamma.

Cutting edge: TREM-like transcript-1, a platelet immunoreceptor tyrosine-based inhibition motif encoding costimulatory immunoreceptor that enhances, rather than inhibits, calcium signaling via SHP-2.

To date, immunoreceptor tyrosine-based inhibition motifs (ITIMs) have been shown to mediate inhibitory properties. We report a novel triggering receptor expressed on myeloid cells (TREM) family member, TREM-like transcript-1 (TLT1), which differs from the activating members because its cytoplasmic tail contains two ITIMs at Y245 and Y281. A TLT1 splice variant (TLT1sp) encodes a different cytoplasmic tail lacking ITIMs.

Characterization of the CD200 receptor family in mice and humans and their interactions with CD200.

CD200 (OX2) is a broadly distributed cell surface glycoprotein that interacts with a structurally related receptor (CD200R) expressed on rodent myeloid cells and is involved in regulation of macrophage function. We report the first characterization of human CD200R (hCD200R) and define its binding characteristics to hCD200. We also report the identification of a closely related gene to hCD200R, designated hCD200RLa, and four mouse CD200R-related genes (termed mCD200RLa-d).

CD200 and membrane protein interactions in the control of myeloid cells.

OX2 (now designated CD200) is a membrane protein expressed by a broad range of cell types. It is the ligand for a receptor restricted to myeloid cells, with the potential to deliver inhibitory signals. This is indicated by the CD200-deficient mouse model, in which myeloid cells are more activated when stimulated immunologically than cells from normal mice.