Enhancing Intrapleural Hyperthermic Chemotherapy for Lung Cancer: Insights from 3D and PDX Models.

: Malignant pleural effusion (MPE) in lung cancer indicates systemically disseminated advanced lung cancer and is associated with poor survival. Intrapleural hyperthermic chemotherapy (IPHC) is a promising treatment for MPE; however, its biological basis is not fully understood. IPHC can enhance anticancer drug efficacy, particularly in drug-resistant cancers.

OCT4-induced oligodendrocyte progenitor cells promote remyelination and ameliorate disease.

The generation of human oligodendrocyte progenitor cells (OPCs) may be therapeutically valuable for human demyelinating diseases such as multiple sclerosis. Here, we report the direct reprogramming of human somatic cells into expandable induced OPCs (iOPCs) using a combination of OCT4 and a small molecule cocktail. This method enables generation of A2B5 (an early marker for OPCs) iOPCs within 2 weeks retaining the ability to differentiate into MBP-positive mature oligodendrocytes.

Activation of CXCL12-CXCR4 signalling induces conversion of immortalised embryonic kidney cells into cancer stem-like cells.

Cancer stem cells (CSCs) have been implicated in the growth and progression of several types of human cancer. The technology to derive and establish CSCs could be a critical tool for understanding cancer and developing new therapeutic targets. In this study, we derived expandable CD15 induced CSCs (iCSCs) from immortalised 293FT human epithelial cells by co-culture with human bone marrow-derived mesenchymal stem cells (BM-MSCs) as feeder cells .

Tissue inhibitor of metalloproteinase proteins inhibit teratoma growth in mice transplanted with pluripotent stem cells.

Pluripotent stem cells (PSCs) can serve as an unlimited cell source for transplantation therapies for treating various devastating diseases, such as cardiovascular diseases, diabetes, and Parkinson's disease. However, PSC transplantation has some associated risks, including teratoma formation from the remaining undifferentiated PSCs. Thus, for successful clinical application, it is essential to ablate the proliferative PSCs before or after transplantation.

Neural stem cells and the secreted proteins TIMPs ameliorate UVB-induced skin photodamage.

UV-induced skin damage is involved in ROS overproduction and the overexpression of matrix metalloproteinases (MMPs), which are inhibited by TIMPs (tissue inhibitor of neural stem cells (NSCs)). These proteins may be associated with skin regeneration through the activation of TIMP proteins, but there have been no reports of treatment of skin photodamage using NSCs and their secreted proteins TIMP-1 and TIMP-2. Here we investigated the photoprotective role of NSCs and their TIMP proteins for the inhibition of UVB-irradiation damage in fibroblasts in SKH-1 mice.

Precise nanoinjection delivery of plasmid DNA into a single fibroblast for direct conversion of astrocyte.

Direct conversion is a powerful approach to safely generate mature neural lineages with potential for treatment of neurological disorders. Astrocytes play a crucial role in neuronal homeostasis and their dysfunctions contribute to several neurodegenerative diseases. Using a single-cell approach for precision, we describe here a robust method using optimized DNA amounts for the direct conversion of mouse fibroblasts to astrocytes.

Stem cell transplantation for Huntington's diseases.

Therapeutic approaches based on stem cells have received considerable attention as potential treatments for Huntington's disease (HD), which is a fatal, inherited neurodegenerative disorder, caused by progressive loss of GABAergic medium spiny neurons (MSNs) in the striatum of the forebrain. Transplantation of stem cells or their derivatives in animal models of HD, efficiently improved functions by replacing the damaged or lost neurons. In particular, neural stem cells (NSCs) for HD treatments have been developed from various sources, such as the brain itself, the pluripotent stem cells (PSCs), and the somatic cells of the HD patients.

Induced neural stem cells as a means of treatment in Huntington's disease.

Huntington's disease (HD) is an inherited neurodegenerative disease characterized by chorea, dementia, and depression caused by progressive nerve cell degeneration, which is triggered by expanded CAG repeats in the huntingtin (Htt) gene. Currently, there is no cure for this disease, nor is there an effective medicine available to delay or improve the physical, mental, and behavioral severities caused by it. Areas covered: In this review, the authors describe the use of induced neural stem cells (iNSCs) by direct conversion technology, which offers great advantages as a therapeutic cell type to treat HD.

A combination of small molecules directly reprograms mouse fibroblasts into neural stem cells.

The generation of induced neural stem cells (iNSCs) from somatic cells using defined factors provides new avenues for basic research and cell therapies for various neurological diseases, such as Parkinson's disease, Huntington's disease, and spinal cord injuries. However, the transcription factors used for direct reprogramming have the potential to cause unexpected genetic modifications, which limits their potential application in cell therapies. Here, we show that a combination of four chemical compounds resulted in cells directly acquiring a NSC identity; we termed these cells chemically-induced NSCs (ciNSCs).

Neural Stem Cells Restore Hair Growth Through Activation of the Hair Follicle Niche.

Several types of hair loss result from the inability of hair follicles to initiate the anagen phase of the hair regeneration cycle. Modulating signaling pathways in the hair follicle niche can stimulate entry into the anagen phase. Despite much effort, stem cell-based or pharmacological therapies to activate the hair follicle niche have not been successful.

Intrathecal Transplantation of Embryonic Stem Cell-Derived Spinal GABAergic Neural Precursor Cells Attenuates Neuropathic Pain in a Spinal Cord Injury Rat Model.

Neuropathic pain following spinal cord injury (SCI) is a devastating disease characterized by spontaneous pain such as hyperalgesia and allodynia. In this study, we investigated the therapeutic potential of ESC-derived spinal GABAergic neurons to treat neuropathic pain in a SCI rat model. Mouse embryonic stem cell-derived neural precursor cells (mESC-NPCs) were cultured in media supplemented with sonic hedgehog (SHH) and retinoic acid (RA) and efficiently differentiated into GABAergic neurons.

Generation of induced pluripotent stem cells without genetic defects by small molecules.

The generation of induced pluripotent stem cells (iPSCs) often causes genetic and epigenetic defects, which may limit their clinical applications. Here, we show that reprogramming in the presence of small molecules preserved the genomic stability of iPSCs by inhibiting DNA double-strand breaks (DSBs) and activating Zscan4 gene. Surprisingly, the small molecules protected normal karyotype by facilitating repair of the DSBs that occurred during the early reprogramming process and long-term culture of iPSCs.

Efficient reprogramming of mouse fibroblasts to neuronal cells including dopaminergic neurons.

Somatic cells were directly converted to functional neurons through the use of a combination of transcription factors, including Ascl1, Brn2, and Myt1l. However, a major limitation is the lack of a reliable source of cell-replacement therapy for neurological diseases. Here, we show that a combination of the transcription factors Ascl1 and Nurr1 (AN) and neurotrophic factors including SHH and FGF8b directly reprogrammed embryonic mouse fibroblasts to induced neuronal (iN) cells: pan-neuronal cells and dopaminergic (DA) neurons under our systematic cell culture conditions.

Stem cell therapy and cellular engineering for treatment of neuronal dysfunction in Huntington's disease.

Huntington's disease (HD) is a fatal inherited neurodegenerative disorder characterized by progressive loss of neurons in the striatum, a sub-cortical region of the forebrain. The sub-cortical region of the forebrain is associated with the control of movement and behavior, thus HD initially presents with coordination difficulty and cognitive decline. Recent reprogramming technologies, including induced pluripotent stem cells (iPSCs) and induced neural stem cells (iNSCs), have created opportunities to understand the pathological cascades that underlie HD and to develop new treatments for this currently incurable neurological disease.

Neural stem cells inhibit melanin production by activation of Wnt inhibitors.

Background: Melanin for skin pigmentation is synthesized from tyrosine via an enzymatic cascade that is controlled by tyrosinase (TYR), tyrosinase-related protein 1 (TRP1), and dopachrome tautomerase/tyrosinase related protein 2 (Dct/TRP2), which are the targets of microphthalmia-associated transcription factor (MITF). MITF is a master regulator of pigmentation and a target of β-catenin in Wnt/β-catenin signaling during melanocyte differentiation. Stem cells have been used in skin pigmentation studies, but the mechanisms were not determined for the conditioned medium (CM)-mediated effects.

Characterization of Oct4-GFP spermatogonial stem cell line and its application in the reprogramming studies.

Establishment of mouse spermatogonial stem cell (SSC) culture systems offers a useful stem cell model for studies of proliferation and self-renewal of mammalian germline stem cells. In addition, spontaneous development of pluripotent stem cells from cultured SSCs emphasizes their possible applications in regenerative medicine as a substitute for embryonic stem cells (ESCs). These pluripotent stem cells termed multipotent germline stem cells (mGSCs) or germline-derived pluripotent stem cells (gPSCs) exhibit almost identical properties in terms of morphology and gene expression patterns to mouse ESCs (mESCs).