Utilizing stem cell-secreted molecules as a versatile toolbox for skin regenerative medicine.

Stem cells are recognized as an important target and tool in regenerative engineering. In this study, we explored the feasibility of engineering amniotic fluid-derived mesenchymal stem cell-secreted molecules (afMSC-SMs) as a versatile bioactive material for skin regenerative medicine applications in a time- and cost-efficient and straightforward manner. afMSC-SMs, obtained in powder form through ethanol precipitation, effectively contributed to preserving the self-renewal capacity and differentiation potential of primary human keratinocytes (pKCs) in a xeno-free environment, offering a potential alternative to traditional culture methods for their long-term in vitro expansion, and allowed them to reconstitute a fully stratified epithelium sheet on human dermal fibroblasts.

Human induced neural stem cells support functional recovery in spinal cord injury models.

Spinal cord injury (SCI) is a clinical condition that leads to permanent and/or progressive disabilities of sensory, motor, and autonomic functions. Unfortunately, no medical standard of care for SCI exists to reverse the damage. Here, we assessed the effects of induced neural stem cells (iNSCs) directly converted from human urine cells (UCs) in SCI rat models.

Establishment of Immortalized Human Endometriotic Stromal Cell Line from Ectopic Lesion of a Patient with Endometriosis.

Endometriosis is an estrogen-dependent inflammatory disease characterized by the growth of endometrial-like tissues containing endometrial stromal cells and glandular epithelium outside the uterine cavity. An insufficient response to progesterone contributes to disease progression and systemic inflammation during the pathogenesis of endometriosis. Patients with endometriosis usually experience painful symptoms, dysmenorrhea, and infertility, which contribute to a significant reduction in their quality of life.

Self-replicative mRNA-mediated generation of induced pluripotent stem cell line from a 1-year-old Leigh syndrome patient with mitochondrial DNA cytochrome b mutation.

Leigh syndrome is a progressive neurodegenerative disease due to defects in the mitochondrial genes, including mitochondrial DNA cytochrome b (MTCYB) mutation, that typically begins in infancy or early childhood. Exercise intolerance and fatigue are common symptoms of mitochondrial disorders. Here, we generated induced pluripotent stem cell (iPSC) line from a 1-year-old patient with Leigh syndrome with MTCYB through temporal expression of exogenes, synthetic self-replicative mRNAs which were regulated by B18R protein.

Generation of a WA14 hESC sub-line carrying a hemizygous ABCD1 (C.1696_1710 del) mutation introduced by CRISPR/Cas9 technology.

ATP-binding cassette transporter subfamily D member 1 (ABCD1) gene is a member of ABC transporter super family, which conduct peroxisomal import of very long chain fatty acid and crucial underlying factor that induces X-linked adrenoleukodystrophy (X-ALD) when the gene is defected. Here, we report the generation of a human embryonic stem cell sub-line harboring a hemizygous ABCD1 mutation (C.1696_1710 del) using CRISPR/Cas9 system.

Isolation of mesenchymal stem cells from Pap smear samples.

Objective: Exploiting their ability to differentiate into mesenchymal lineages like cartilage, bone, fat, and muscle, and to elicit paracrine effects, mesenchymal stem cells (MSCs) are widely used in clinical settings to treat tissue injuries and autoimmune disorders. One of accessible sources of MSC is the samples used for Papanicolaou (Pap) test, which is a cervical screening method for detecting potentially pre-cancerous and cancerous alterations in the cervical cells and to diagnose genetic abnormalities in fetuses. This study aimed to identify and isolate the stem cells from Pap smear samples collected from pregnant women, and to trace the origin of these cells to maternal or fetal tissue, and characterize their stem cell properties.

mRNA-Driven Generation of Transgene-Free Neural Stem Cells from Human Urine-Derived Cells.

Human neural stem cells (NSCs) hold enormous promise for neurological disorders, typically requiring their expandable and differentiable properties for regeneration of damaged neural tissues. Despite the therapeutic potential of induced NSCs (iNSCs), a major challenge for clinical feasibility is the presence of integrated transgenes in the host genome, contributing to the risk for undesired genotoxicity and tumorigenesis. Here, we describe the advanced transgene-free generation of iNSCs from human urine-derived cells (HUCs) by combining a cocktail of defined small molecules with self-replicable mRNA delivery.

Overexpression of Nanog in amniotic fluid-derived mesenchymal stem cells accelerates dermal papilla cell activity and promotes hair follicle regeneration.

Alopecia, one of the most common chronic diseases, can seriously affect a patient's psychosocial life. Dermal papilla (DP) cells serve as essential signaling centers in the regulation of hair growth and regeneration and are associated with crosstalk between autocrine/paracrine factors and the surrounding environment. We previously demonstrated that amniotic fluid-derived mesenchymal stem cell-conditioned medium (AF-MSC-CM) accelerates hair regeneration and growth.

Generation of an induced pluripotent stem cell (iPSC) line from a 42-year-old adult cerebral type X-linked adrenoleukodystrophy (X-ALD) patient.

X-linked Adrenoleukodystrophy (X-ALD) is a neuro-metabolic disorder that is caused by malfunction of a peroxisomal transporter protein, adenosine ATP-binding cassette transporter superfamily D member 1 (ABCD1). We established an induced pluripotent stem cell (iPSC) line from a 42-year-old male X-ALD patient-derived dermal fibroblasts with Sendai virus-mediated reprogramming. Established iPSCs stably expanded, expressed genes of pluripotency, and maintained normal karyotype.

Generation of Anterior Hindbrain-Specific, Glial-Restricted Progenitor-Like Cells from Human Pluripotent Stem Cells.

Engraftment of oligodendrocyte progenitor cells (OPCs), which form myelinating oligodendrocytes, has the potential to treat demyelinating diseases such as multiple sclerosis. However, conventional strategies for generating oligodendrocytes have mainly focused on direct differentiation into forebrain- or spinal cord-restricted oligodendrocytes without establishing or amplifying stem/progenitor cells. Taking advantage of a recently established culture system, we generated expandable EN1- and GBX2-positive glial-restricted progenitor-like cells (GPLCs) near the anterior hindbrain.

Glycine decarboxylase regulates the maintenance and induction of pluripotency via metabolic control.

Reprogramming of 'adult' differentiated somatic cells to 'embryonic' pluripotent stem cells accompanied by increased rate of glycolysis. Conversely, glycolysis triggers accumulation of advanced glycation end products (AGEs), a potential causative factor in aging, by promoting methylglyoxal production. Therefore, it is reasonable that pluripotent stem cells (PSCs) would specifically regulate glycolysis to maintain their embryonic features.

Inhibitory effect of celastrol on adipogenic differentiation of human adipose-derived stem cells.

Control of adipogenesis in mesenchymal stem cells (MSCs) offers enormous potential for management of obesity- and aging-related diseases. Celastrol, the traditional Chinese medicine extracted from Tripterygium wilfordi, exhibits anti-obesity effects in in vitro and in vivo murine models. This study describes how celastrol affects multilineage differentiation potential of human adipose-derived stem cells (hADSCs).

Generation of induced pluripotent stem cell (iPSC) line from a 21-year-old X-linked adrenoleukodystrophy (X-ALD) patient.

X-linked Adrenoleukodystrophy (X-ALD) is a genetic disease that caused by mutations in adenosine triphosphate [ATP]-binding-cassette transporter superfamily D member 1 (ABCD1) gene. We generated an induced pluripotent stem cell (iPSC) line from a 21-year-old male X-ALD patient-derived fibroblasts by Sendai virus mediated reprogramming. Established iPSCs stably expanded while maintaining immunoreactivity for various pluripotency markers and alkaline phosphatase, as well as normal 44+XY karyotype.

Generation of two induced pluripotent stem cell (iPSC) lines from X-linked adrenoleukodystrophy (X-ALD) patients with adrenomyeloneuropathy (AMN).

X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder caused by a mutation in the ATP-binding cassette transporter subfamily D member 1 (ABCD1) gene. We generated two induced pluripotent stem cell (iPSC) lines from X-ALD patients with adrenomyeloneuropathy (AMN) by Sendai virus containing OCT4, SOX2, KLF4 and c-MYC. Established iPSC lines expressed various pluripotency markers, had differentiation potential of three germ layers in vitro, had normal karyotype and retained ABCD1 mutation.

Generation of induced pluripotent stem cell (iPSC) line from Charcot-Marie-Tooth disease patient with MPZ mutation (CMT1B).

Charcot-Marie-Tooth disease (CMT1B) is an inherited neurological disorder caused by mutation of the myelin protein zero (MPZ) gene. We generated an induced pluripotent stem cell (iPSC) line from an 81-year-old patient with CMT1B by electroporating of lymphoblastoid cell lines with episomal plasmids encoding OCT4, SOX2, KLF4, L-MYC, LIN28, and p53-targeting shRNA. The established iPSCs expressed various pluripotency markers, demonstrated the potential to differentiate into cells of the three germ layers in vitro, had a normal karyotype and retained the MPZ mutation.

Generation of induced pluripotent stem cell (iPSC) line from a 36-year-old Charcot-Marie-Tooth disease patient with GJB1 mutation (CMTX).

Charcot-Marie-Tooth disease (CMTX) is inherited neurological disorder caused by gap junction beta 1 gene (GJB1) mutation. We generated induced pluripotent stem cell (iPSC) line from 36-year-old CMTX disease patient by electroporation of skin fibroblasts with episomal vectors encoding OCT4, SOX2, KLF4, L-MYC, LIN28 and shRNA-p53. Established iPSCs expressed various pluripotency markers, had differentiation potential of three germ layers in vitro, had normal karyotype and retained GJB1 mutation.