Efficacy of vocal fold injection of dedifferentiated fat cells in treating glottis closure insufficiency: Insights from a rat model of recurrent laryngeal nerve resection.

Glottic insufficiency results from impaired vocal fold contact, leading to a gap between the folds and manifesting as hoarseness and respiratory difficulties. Vocal folds injection is a commonly utilized therapeutic approach to rectify this gap by augmenting vocal folds volume; however, the optimal injectable material remains undetermined. Dedifferentiated fat cells (DFATs), derived from mature adipocytes, exhibit robust proliferative capacity and multipotency, establishing them as potential candidates for treating glottic insufficiency.

Regeneration of Two-Walled Infrabony Periodontal Defects in Swine After Buccal Fat Pad-Derived Dedifferentiated Fat Cell Autologous Transplantation.

Mature adipocyte-derived dedifferentiated fat (DFAT) cells show proliferative capabilities and multipotency. Given that the buccal fat pad (BFP) serves as a readily available resource for DFAT cell isolation, BFP-derived DFAT (BFP-DFAT) cells are a promising candidate in orofacial tissue engineering. In this research, we assessed the regenerative capacity of the periodontium through autologous BFP-DFAT cell transplantation in adult swine (micro-minipigs; MMPs).

C3H10T1/2 Mesenchymal Stem Cell Line as a New In Vitro Tool for Studying Adipocyte Dedifferentiation.

Dedifferentiated fat (DFAT) cells are adipocyte-derived cells that are able to differentiate into multiple cell lineages such as adipocytes, osteoblasts and chondrocytes, similar to mesenchymal stem cells (MSCs). Despite their great potential for developing novel clinical interventions by using their multipotency, the detailed mechanisms of how adipocytes undergo dedifferentiation into DFAT cells are not completely understood, because useful in vitro tools for studying adipocyte dedifferentiation are missing. In this study, we show that mature adipocytes derived from the MSC cell line C3H10T1/2 underwent dedifferentiation into cells with DFAT cell-like characteristics, when they were cultured in an inverted flask.

Muscle regeneration therapy using dedifferentiated fat cell (DFAT) for anal sphincter dysfunction.

Purpose: We investigated the effects of mouse-derived DFAT on the myogenic differentiation of a mouse-derived myoblast cell line (C2C12) and examined the therapeutic effects of rat-derived DFAT on anal sphincter injury using a rat model.

Methods: C2C12 cells were cultured using DMEM and DFAT-conditioned medium (DFAT-CM), evaluating MyoD and Myogenin gene expression via RT-PCR. DFAT was locally administered to model rats with anorectal sphincter dysfunction 3 days post-CTX injection.

2α-Substituted Vitamin D Derivatives Effectively Enhance the Osteoblast Differentiation of Dedifferentiated Fat Cells.

The active form of vitamin D, 1α,25-dihydroxyvitamin D [1,25(OH)D], is a principal regulator of calcium homeostasis through activation of the vitamin D receptor (VDR). Previous studies have shown that 2α-(3-hydroxypropyl)-1,25D (O1C3) and 2α-(3-hydroxypropoxy)-1,25D (O2C3), vitamin D derivatives resistant to inactivation enzymes, can activate VDR, induce leukemic cell differentiation, and increase blood calcium levels in rats more effectively than 1,25(OH)D. In this study, to further investigate the usefulness of 2α-substituted vitamin D derivatives, we examined the effects of O2C3, O1C3, and their derivatives on VDR activity in cells and mouse tissues and on osteoblast differentiation of dedifferentiated fat (DFAT) cells, a cell type with potential therapeutic application in regenerative medicine.

Abnormal epigenetic memory of mesenchymal stem and progenitor cells caused by fetal malnutrition induces hypertension and renal injury in adulthood.

Fetal malnutrition has been reported to induce hypertension and renal injury in adulthood. We hypothesized that this hypertension and renal injury would be associated with abnormal epigenetic memory of stem and progenitor cells contributing to organization in offspring due to fetal malnutrition. We measured blood pressure (BP) for 60 weeks in offspring of pregnant rats fed a normal protein diet (Control), low-protein diet (LP), and LP plus taurine (LPT) in the fetal period.

Therapeutic potential of dedifferentiated fat cells in a rat model of osteoarthritis of the knee.

Introduction: Mature adipocyte-derived dedifferentiated fat cells (DFATs) represent a subtype of multipotent cells that exhibit comparable phenotypic and functional characteristics to adipose-derived stem cells (ASCs). In this study, we assessed the chondroprotective properties of intra-articularly administrated DFATs in a rat model of osteoarthritis (OA). We also investigated in vitro the expression of anti-inflammatory and chondroprotective genes in DFATs prepared from the infrapatellar fat pad (IFP) and subcutaneous adipose-tissue (SC) of human origin.

Development of multifunctional pyrrole-imidazole polyamides that increase hepatocyte growth factor and suppress transforming growth factor-β1.

Purpose: The DNA recognition peptide compounds pyrrole-imidazole (PI) polyamides bind to the minor groove and can block the binding of transcription factors to target sequences. To develop more PI polyamides as potential treatments for fibrotic diseases, including chronic renal failure, we developed multifunctional PI polyamides that increase hepatocyte growth factor (HGF) and decrease transforming growth factor (TGF)-β1.

Methods: We designed seven PI polyamides (HGF-1 to HGF-7) that bind to the chicken ovalbumin upstream promoter transcription factor-1 (COUP-TF1) binding site of the HGF promoter sequence.

Syntheses of 25-Adamantyl-25-alkyl-2-methylidene-1α,25-dihydroxyvitamin D Derivatives with Structure-Function Studies of Antagonistic and Agonistic Active Vitamin D Analogs.

The active form of vitamin D, 1α,25-dihydroxyvitamin D [1,25(OH)D], is a major regulator of calcium homeostasis through activation of the vitamin D receptor (VDR). We have previously synthesized vitamin D derivatives with large adamantane (AD) rings at position 24, 25, or 26 of the side chain to study VDR agonist and/or antagonist properties. One of them-ADTK1, with an AD ring and 23,24-triple bond-shows a high VDR affinity and cell-selective VDR activity.

Dedifferentiated fat cells administration ameliorates abnormal expressions of fatty acids metabolism-related protein expressions and intestinal tissue damage in experimental necrotizing enterocolitis.

Neonatal necrotizing enterocolitis (NEC) is a serious disease of premature infants that necessitates intensive care and frequently results in life-threatening complications and high mortality. Dedifferentiated fat cells (DFATs) are mesenchymal stem cell-like cells derived from mature adipocytes. DFATs were intraperitoneally administrated to a rat NEC model, and the treatment effect and its mechanism were evaluated.

Bone marrow-derived dedifferentiated fat cells exhibit similar phenotype as bone marrow mesenchymal stem cells with high osteogenic differentiation and bone regeneration ability.

Background: Mesenchymal stem cells (MSCs) are known to have different differentiation potential depending on the tissue of origin. Dedifferentiated fat cells (DFATs) are MSC-like multipotent cells that can be prepared from mature adipocytes by ceiling culture method. It is still unknown whether DFATs derived from adipocytes in different tissue showed different phenotype and functional properties.

Development of gene silencer pyrrole-imidazole polyamides targeting GSK3β for treatment of polycystic kidney diseases.

The cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB)-glycogen synthase kinase 3β (GSK3β) signaling pathway was reported to be involved in the progression of autosomal dominant polycystic kidney diseases (ADPKD). We designed and synthesized pyrrole-imidazole (PI) polyamides as novel gene-silencers to prevent binding of CREB on the GSK3β gene promoter and examined the effects of the PI polyamides on proliferation and cyst formation of mouse collecting duct M1 cells. The GSK3β PI polyamides significantly inhibited expression of GSK3β mRNA in M1 cells with forskolin.

Effects of dedifferentiated fat cells on neurogenic differentiation and cell proliferation in neuroblastoma cells.

Purpose: Mesenchymal stem cells (MSCs) can induce differentiation of neuroblastoma (NB) cells. Properties of dedifferentiated fat cells (DFATs) are similar to those of MSCs. Here, we investigated whether DFATs can induce NB cell differentiation and suppress cell proliferation.

Implantation of dedifferentiated fat cells ameliorated antineutrophil cytoplasmic antibody glomerulonephritis by immunosuppression and increases in tumor necrosis factor-stimulated gene-6.

Introduction: The implantation of dedifferentiated fat (DFAT) cells has been shown to exert immunosuppressive effects. To develop DFAT cell therapy for antineutrophil cytoplasmic antibody (ANCA) glomerulonephritis, the effects of the implantation of DFAT cells on ANCA glomerulonephritis were investigated in mice.

Methods: PKH26-labeled DFAT cells (10) were infused through the posterior orbital venous plexus to investigate delivery of DFAT cells in ICR mice.

Transplantation of Mature Adipocyte-Derived Dedifferentiated Fat Cells Facilitates Periodontal Tissue Regeneration of Class II Furcation Defects in Miniature Pigs.

Adipose tissue is composed mostly of adipocytes that are in contact with capillaries. By using a ceiling culture method based on buoyancy, lipid-free fibroblast-like cells, also known as dedifferentiated fat (DFAT) cells, can be separated from mature adipocytes with a large single lipid droplet. DFAT cells can re-establish their active proliferation ability and transdifferentiate into various cell types under appropriate culture conditions.

Urethral injection of dedifferentiated fat cells ameliorates sphincter damage and voiding dysfunction in a rat model of persistence stress urinary incontinence.

Purpose: Dedifferentiated fat (DFAT) cells are mature adipocyte-derived multipotent cells that can be applicable to cell-based therapy for stress urinary incontinence (SUI). This study developed a persistence SUI model that allows long-term evaluation using a combination of vaginal distention (VD) and bilateral ovariectomy (OVX) in rats. Then, the therapeutic effects of DFAT cell transplantation in the persistence SUI model was examined.

Phenotypic and functional properties of dedifferentiated fat cells derived from infrapatellar fat pad.

Introduction: Mature adipocyte-derived dedifferentiated fat cells (DFATs) are mesenchymal stem cell (MSC)-like cells with high proliferative ability and multilineage differentiation potential. In this study, we first examined whether DFATs can be prepared from infrapatellar fat pad (IFP) and then compared phenotypic and functional properties of IFP-derived DFATs (IFP-DFATs) with those of subcutaneous adipose tissue (SC)-derived DFATs (SC-DFATs).

Methods: Mature adipocytes isolated from IFP and SC in osteoarthritis patients (n = 7) were cultured by ceiling culture method to generate DFATs.

Quantitative Analysis of Factors Regulating Angiogenesis for Stem Cell Therapy.

(1) Background: The control of angiogenesis is essential in disease treatment. We investigated angiogenesis-promoting or -suppressing factors and their molecular mechanisms. (2) Methods: Angiogenesis from HUVECs was quantitatively analyzed using the Angiogenesis Analysis Kit (Kurabo, Osaka, Japan).

Antinuclear antibodies produced in HLA-DR transgenic humanized mice developed chronic graft-versus-host disease.

Background: Chronic graft versus host disease (GVHD) has been reported in humanized mice after the implantation of human hematopoietic stem cells (hu-HSC). As such, humanized mice have been applied to a mouse model of chronic GVHD; however, B-cell activation and autoantibody production did not occur, and the clinical features of chronic GVHD were not sufficiently reproduced. The purpose of this study was to establish an improved humanized mouse model with chronic GVHD using HLA-DR transgenic NOD/Shi-scid, IL-2RγKO (NOG) mice.

Transcriptional Suppression of Diabetic Nephropathy with Novel Gene Silencer Pyrrole-Imidazole Polyamides Preventing USF1 Binding to the TGF-β1 Promoter.

Upstream stimulatory factor 1 (USF1) is a transcription factor that is increased in high-glucose conditions and activates the transforming growth factor (TGF)-β1 promoter. We examined the effects of synthetic pyrrole-imidazole (PI) polyamides in preventing USF1 binding on the TGF-β1 promoter in Wistar rats in which diabetic nephropathy was established by intravenous administration of streptozotocin (STZ). High glucose induced nuclear localization of USF1 in cultured mesangial cells (MCs).

Randomized trial of granulocyte colony-stimulating factor for spinal cord injury.

Attenuation of the secondary injury of spinal cord injury (SCI) can suppress the spread of spinal cord tissue damage, possibly resulting in spinal cord sparing that can improve functional prognoses. Granulocyte colony-stimulating factor (G-CSF) is a haematological cytokine commonly used to treat neutropenia. Previous reports have shown that G-CSF promotes functional recovery in rodent models of SCI.

Umbilical artery tissue contains p75 neurotrophin receptor-positive pericyte-like cells that possess neurosphere formation capacity and neurogenic differentiation potential.

Introduction: The p75 neurotrophin receptor (p75NTR) is known as an efficient marker for the prospective isolation of mesenchymal stem cells (MSCs) and neural crest-derived stem cells (NCSCs). To date, there is quite limited information concerning p75NTR-expressing cells in umbilical cord (UC), although UC is known as a rich source of MSCs. We show for the first time the localization, phenotype, and functional properties of p75NTR cells in UC.

Isolation and characterization of neural crest-like progenitor cells in human umbilical cord blood.

Introduction: Neural crest (NC)-like stem/progenitor cells provide an attractive cell source for regenerative medicine because of their multipotent property and ease of isolation from adult tissue. Although human umbilical cord blood (HUCB) is known to be a rich source of stem cells, the presence of the NC-like stem/progenitor cells in HUCB remains to be elucidated. In this study, we have isolated NC-like progenitor cells using an antibody to p75 neurotrophin receptor (p75NTR) and examined their phenotype and stem cell function in vitro.