Regulatory Oversight of Cell, Tissue, and Gene Therapy Products in Singapore.

The Health Sciences Authority of Singapore has implemented a fit-for-purpose regulatory framework for Cell, Tissue, and Gene Therapy Products (CTGTPs) on 1 March 2021. A total of 11 pieces of subsidiary legislation for CTGTP are gazetted under the Health Products Act as Health Products (CTGTP) Regulations 2021. The CTGTPs are stratified into lower-risk Class 1 CTGTP or moderate- to higher-risk Class 2 CTGTP based on their degree of manipulation, intended use, and if they are combined or used with therapeutic products or medical devices.

Regulatory Oversight of Cell- and Tissue-Based Therapeutic Products and Gene Therapy Products in Singapore.

The regulatory environment for cell- and tissue-based therapeutic products and gene therapy products is rapidly evolving and drug regulatory agencies are working towards establishing a risk-based system in the regulatory framework. Similarly in Singapore, a risk-based tiered approach has been applied whereby clinical trials and product licence of high-risk cell- and tissue-based therapeutic products (substantially manipulated products, products intended for nonhomologous use or combined products) and gene therapy products are regulated as medicinal products under the Medicines Act. There is no legal definition for cell- and tissue-based therapeutic and gene therapy products.

Cell origin of human mesenchymal stem cells determines a different healing performance in cardiac regeneration.

The possible different therapeutic efficacy of human mesenchymal stem cells (hMSC) derived from umbilical cord blood (CB), adipose tissue (AT) or bone marrow (BM) for the treatment of myocardial infarction (MI) remains unexplored. This study was to assess the regenerative potential of hMSC from different origins and to evaluate the role of CD105 in cardiac regeneration. Male SCID mice underwent LAD-ligation and received the respective cell type (400.

Retraction: Mesenchymal Stem Cells: Are They Suitable for Systemic Injection? An In Vitro Study.

This article is being retracted because another article was published using the same data, but under a different title, in Microvascular Research.

Intracardiac injection of erythropoietin induces stem cell recruitment and improves cardiac functions in a rat myocardial infarction model.

Erythropoietin (EPO) protects the myocardium from ischaemic injury and promotes beneficial remodelling. We assessed the therapeutic efficacy of intracardiac EPO injection and EPO-mediated stem cell homing in a rat myocardial infarction (MI) model. Following MI, EPO (3000 U/kg) or saline was delivered by intracardiac injection.

Localized SDF-1alpha gene release mediated by collagen substrate induces CD117 stem cells homing.

Stromal cell-derived factor-1alpha (SDF-1alpha) mediated mobilization and homing of stem cells showed promising potential in stem cell based tissue engineering and regenerative medicine. However local and sustained release of SDF-1alpha is indispensable for stem cell mediated regenerative process due to its short half-life under inflammatory conditions. In this study, a gene activated collagen substrate (GAC) was formed via assembly of plasmid encoding SDF-1alpha into a collagen substrate to create a microenvironment favoring stem cell homing.

Is the intravascular administration of mesenchymal stem cells safe? Mesenchymal stem cells and intravital microscopy.

We investigated the kinetics of human mesenchymal stem cells (MSCs) after intravascular administration into SCID mouse cremaster vasculature by intravital microscopy. MSCs were injected into abdominal aorta through left femoral artery at two different concentrations (1 x 10(6) or 0.2 x 10(6) cell).

Efficacy of remote ischaemic preconditioning for spinal cord protection against ischaemic injury: association with heat shock protein expression.

Introduction: We aimed to determine the efficacy of remote ischaemic preconditioning in the hind limb of rats for ischaemic damage of the spinal cord through neurological and histological investigation and examination of heat shock proteins (HSP).

Material And Methods: Thirty male Sprague-Dawley rats were divided into three groups as Group 1 (control group, n=10), Group 2 (ischaemia control group, n=10), and Group 3 (remote ischaemia preconditioning group, n=10). The right lower limb of the rats in the study group was compressed with a tourniquet for three cycles of ten-minute ischaemia followed by ten-minute reperfusion.

Enhanced thoracic gene delivery by magnetic nanobead-mediated vector.

Background: Systemic gene delivery is limited by the adverse hydrodynamic conditions on the collection of gene carrier particles to the specific area. In the present study, a magnetic field was employed to guide magnetic nanobead (MNB)/polymer/DNA complexes after systemic administration to the left side of the mouse thorax in order to induce localized gene expression.

Methods: Nonviral polymer (poly ethyleneimine, PEI) vector-gene complexes were conjugated to MNBs with the Sulfo-NHS-LC-Biotin linker.

Endothelial NOS is required for SDF-1alpha/CXCR4-mediated peripheral endothelial adhesion of c-kit+ bone marrow stem cells.

In the era of intravascular approaches for regenerative cell therapy, the underlying mechanisms of stem cell migration to non-marrow tissue have not been clarified. We hypothesized that next to a local inflammatory response implying adhesion molecule expression, endothelial nitric oxide synthase (eNOS)-dependent signaling is required for stromal- cell-derived factor-1 alpha (SDF-1alpha)-induced adhesion of c-kit+ cells to the vascular endothelium. SDF-1alpha/tumor necrosis factor-alpha (TNF-alpha)-induced c-kit+-cell shape change and migration capacity was studied in vitro using immunohistochemistry and Boyden chamber assays.

Bcl-2 engineered MSCs inhibited apoptosis and improved heart function.

Engraftment of mesenchymal stem cells (MSCs) derived from adult bone marrow has been proposed as a potential therapeutic approach for postinfarction left ventricular dysfunction. However, limited cell viability after transplantation into the myocardium has restricted its regenerative capacity. In this study, we genetically modified MSCs with an antiapoptotic Bcl-2 gene and evaluated cell survival, engraftment, revascularization, and functional improvement in a rat left anterior descending ligation model via intracardiac injection.

Kinectin-dependent assembly of translation elongation factor-1 complex on endoplasmic reticulum regulates protein synthesis.

Kinectin is an integral membrane protein with many isoforms primarily found on the endoplasmic reticulum. It has been found to bind kinesin, Rho GTPase, and translation elongation factor-1delta. None of the existing models for the quaternary organization of the elongation factor-1 complex in higher eukaryotes involves kinectin.

Distribution and functions of kinectin isoforms.

Kinectin is an integral transmembrane protein on the endoplasmic reticulum, binding to kinesin, interacting with Rho GTPase and anchoring the translation elongation factor-1 complex. There has been debate on the specific role(s) of kinectin in different species and cell types. Here we identified 15 novel kinectin isoforms in the mouse nervous system, constituting a family of alternatively spliced carboxyl-terminal variants.

Cloning of rat telomerase catalytic subunit functional domains, reconstitution of telomerase activity and enzymatic profile of pig and chicken tissues.

Telomerase is a ribonucleoprotein polymerase which adds TTAGGG repeats to telomeric ends. Recent studies reported the reverse transcription enzyme activity mostly from the catalytic subunit (TERT) of the enzyme complex. Both human telomerase catalytic subunit (hTERT) and mouse telomerase catalytic subunit (mTERT) had been previously cloned but not rat telomerase catalytic subunit rTERT.

Kinectin anchors the translation elongation factor-1 delta to the endoplasmic reticulum.

Kinectin has been proposed to be a membrane anchor for kinesin on intracellular organelles. A kinectin isoform that lacks a major portion of the kinesin-binding domain does not bind kinesin but interacts with another resident of the endoplasmic reticulum, the translation elongation factor-1 delta (EF-1 delta). This was shown by yeast two-hybrid analysis and a number of in vitro and in vivo assays.