Evaluation of Safety and Efficacy of Cell Therapy Based on Osteoblasts Derived from Umbilical Cord Mesenchymal Stem Cells for Osteonecrosis of the Femoral Head: Study Protocol for a Single-Center, Open-Label, Phase I Clinical Trial.

Although mesenchymal stem cells (MSCs) insertion has gained recent attention as a joint-preserving procedure, no study has conducted direct intralesional implantation of human umbilical cord-derived MSCs (hUCMSCs) in patients with ONFH. This is a protocol for a phase 1 clinical trial designed to assess the safety and exploratory efficacy of human umbilical cord-derived osteoblasts (hUC-Os), osteogenic differentiation-induced cells from hUCMSCs, in patients with early-stage ONFH. Nine patients with Association Research Circulation Osseous (ARCO) stage 1 or 2 will be assigned to a low-dose (1 × 10 hUC-O cells, = 3), medium-dose (2 × 10 cells, = 3), and high-dose group (4 × 10 cells, = 3) in the order of their arrival at the facility, and, depending on the occurrence of dose-limiting toxicity, up to 18 patients can be enrolled by applying the 3 + 3 escalation method.

Whitening and moisturizing enhancing effects of three-dimensional human adipose-derived mesenchymal stem cell-conditioned medium-containing cream.

Background: High-functional cosmetic products combined with the concept of "treatment" cosmetics are being introduced to the market. Cosmetic products containing a skin-derived microbiome, a three-dimensional (3D) stem cell culture medium, and low-molecular-weight collagen are being introduced, and these products are leading the cosmeceutical market. We aimed to confirm the potential of a 3D stem cell culture medium-containing cream as a skin-whitening and moisturizing product.

In Vitro Tracking of Human Umbilical Vein Endothelial Cells Using Ultra-Sensitive Quantum Dot-Embedded Silica Nanoparticles.

The nanoscale spatiotemporal resolution of single-particle tracking (SPT) renders it a powerful method for exploring single-molecule dynamics in living cells or tissues, despite the disadvantages of using traditional organic fluorescence probes, such as the weak fluorescent signal against the strong cellular autofluorescence background coupled with a fast-photobleaching rate. Quantum dots (QDs), which enable tracking targets in multiple colors, have been proposed as an alternative to traditional organic fluorescence dyes; however, they are not ideally suitable for applying SPT due to their hydrophobicity, cytotoxicity, and blinking problems. This study reports an improved SPT method using silica-coated QD-embedded silica nanoparticles (QD), which represent brighter fluorescence and are less toxic than single QDs.

Comparison of guidelines for biological ancillary materials used for the manufacture of gene and cellular therapy products in Asia.

Background Aims: Although biologiocal ancillay materials (AMs) have specific risk associated with their derivations, it plays key role to manufature cell and gene therapy (CGT) products. It is important to understand the regulation relevant to AMs for developers.

Methods: The authors investigated the guidelines and pharmacopeia (hereinafter referred to as "guidelines") for biological AMs used for the manufacture of CGT products in Asia (China, India, Japan, Korea and Taiwan).

Medroxyprogesterone Reverses Tolerable Dose Metformin-Induced Inhibition of Invasion via Matrix Metallopeptidase-9 and Transforming Growth Factor-β1 in KLE Endometrial Cancer Cells.

This study was performed to evaluate the anticancer effects of tolerable doses of metformin with or without medroxyprogesterone (MPA) in endometrial cancer cells. Cell viability, cell invasion, and levels of matrix metallopeptidase (MMP) and transforming growth factor (TGF)-β1 were analyzed using three human endometrial adenocarcinoma cell lines (Ishikawa, KLE, and uterine serous papillary cancer (USPC)) after treatment with different dose combinations of MPA and metformin. Combining metformin (0, 100, 1000 µM) and 10 µM MPA induced significantly decreased cell viability in a time- and dose-dependent manner in Ishikawa cells, but not in KLE and USPC cells.

Development of a three-dimensional in vitro co-culture model to increase drug selectivity for humans.

Aim: Insulin resistance is a metabolic state where insulin sensitivity is lower than normal condition and strongly related to type 2 diabetes. However, an in vitro model mimicking insulin resistance is rare and thus screening drugs for insulin resistance severely depends on an in vivo model. Here, to increase anti-diabetic drug selectivity for humans, 3D ADMSCs and macrophages were co-cultured with in-house fabricated co-culture plates.

Establishment of stably expandable induced myogenic stem cells by four transcription factors.

Life-long regeneration of healthy muscle by cell transplantation is an ideal therapy for patients with degenerative muscle diseases. Yet, obtaining muscle stem cells from patients is very limited due to their exhaustion in disease condition. Thus, development of a method to obtain healthy myogenic stem cells is required.

Dipeptide-functionalized polyamidoamine dendrimer-mediated apoptin gene delivery facilitates apoptosis of human primary glioma cells.

Glioblastoma multiform (GBM) is the most frequent and aggressive form of brain tumors in adults. However, the development of more efficient and safe nonviral vector gene therapy represents a promising therapeutic approach, using a tumor-specific killer gene, named apoptin. In this study, we describe the efficacy of non-viral gene delivery vectors, the amino acid-conjugated PAMAM derivatives (PAMAM-H-R and PAMAM-H-K) in delivering a therapeutic gene, displaying affinity toward human primary glioma cells (GBL-14 cells) and dermal fibroblasts.

Characterization of glycol chitosan grafted with low molecular weight polyethylenimine as a gene carrier for human adipose-derived mesenchymal stem cells.

Mesenchymal stem cells (MSCs) have a great capacity for self-renewal while still maintaining their multipotency, and can differentiate into a variety of cell types. The delivery of genes to a site of injury is a current and interesting field of gene therapy. In the present study, we describe a nonviral gene delivery carrier, glycol chitosan-methyl acrylate-polyethylenimine (GMP) polymer targeted towards human adipose-derived mesenchymal stem cells (AD-MSCs).

Characterization of basic amino acids-conjugated PAMAM dendrimers as gene carriers for human adipose-derived mesenchymal stem cells.

Since mesenchymal stem cells (MSCs) can self-renew and differentiate into multiple cell types, the delivery of genes to this type of cell can be an important tool in the emerging field of tissue regeneration and engineering. However, development of more efficient and safe nonviral vectors for gene delivery to stem cells in particular still remains a great challenge. In this study, we describe a group of nonviral gene delivery vectors, conjugated PAMAM derivatives (PAMAM-H-R, PAMAM-H-K, and PAMAM-H-O), displaying affinity toward human adipose-derived mesenchymal stem cells (AD-MSCs).

Recurrent variations in DNA methylation in human pluripotent stem cells and their differentiated derivatives.

Human pluripotent stem cells (hPSCs) are potential sources of cells for modeling disease and development, drug discovery, and regenerative medicine. However, it is important to identify factors that may impact the utility of hPSCs for these applications. In an unbiased analysis of 205 hPSC and 130 somatic samples, we identified hPSC-specific epigenetic and transcriptional aberrations in genes subject to X chromosome inactivation (XCI) and genomic imprinting, which were not corrected during directed differentiation.

Comparison of mesenchymal-like stem/progenitor cells derived from supernumerary teeth with stem cells from human exfoliated deciduous teeth.

Aims: Dental tissue has been the focus of attention as an easily accessible postnatal tissue source of high-quality stem cells. Since the first report on the dental pulp stem cells (DPSCs) from permanent third molar teeth, stem cells from human exfoliated deciduous teeth (SHED) were identified as a population distinct from DPSCs. In this study, we compared DPSCs from supernumerary teeth and SHED in three age- and sex-matched patients.

The effects of the physical properties of culture substrates on the growth and differentiation of human embryonic stem cells.

The physical factors of cell-culture environment have received little attention despite their anticipated significant role in human embryonic stem cell (hESC) culture optimization. Here we show that hESC culture conditions can be optimized by utilizing polyethylene terephthalate (PET) membranes whose defined pore densities (PDs) determine membrane surface hardness. The PET membranes with 1-4 × 10(6) pores/cm(2) (0.

Dynamic changes in the copy number of pluripotency and cell proliferation genes in human ESCs and iPSCs during reprogramming and time in culture.

Genomic stability is critical for the clinical use of human embryonic and induced pluripotent stem cells. We performed high-resolution SNP (single-nucleotide polymorphism) analysis on 186 pluripotent and 119 nonpluripotent samples. We report a higher frequency of subchromosomal copy number variations in pluripotent samples compared to nonpluripotent samples, with variations enriched in specific genomic regions.

Promyelocytic leukemia is a direct inhibitor of SAPK2/p38 mitogen-activated protein kinase.

The promyelocytic leukemia gene (PML) encodes a growth/tumor suppressor protein that is essential for the induction of apoptosis in response to various apoptotic signals. The mechanism by which PML plays a role in the regulation of cell death is still unknown. In the current study, we demonstrate that PML negatively regulated the SAPK2/p38 signaling pathway by sequestering p38 from its upstream kinases, MKK3, MKK4, and MKK6, whereas PML did not affect the SAPK1/c-Jun NH(2)-terminal kinase pathway.

Human cytomegalovirus inhibits tapasin-dependent peptide loading and optimization of the MHC class I peptide cargo for immune evasion.

The immune evasion protein US3 of human cytomegalovirus binds to and arrests MHC class I molecules in the endoplasmic reticulum (ER). However, substantial amounts of class I molecules still escape US3-mediated ER retention, suggesting that not all class I alleles are affected equally by US3. Here, we identify tapasin inhibition as the mechanism of MHC retention by US3.

Soluble HLA-G generated by proteolytic shedding inhibits NK-mediated cell lysis.

In contrast to the classical HLA class Ia molecules, the nonclassical HLA-G primary transcript is alternatively spliced to generate several mRNAs that encode four membrane-bound and three soluble isoforms. This study demonstrated that the soluble form of HLA-G can also be generated by metalloproteinase-dependent shedding at post-translational level. These soluble HLA-G1 molecules generated by the cleavage of membrane-bound HLA-G1 associate with beta2-microglobulin and contain bound peptides that are stable at physiological conditions.