Hematopoietic stem-cell senescence and myocardial repair - Coronary artery disease genotype/phenotype analysis of post-MI myocardial regeneration response induced by CABG/CD133+ bone marrow hematopoietic stem cell treatment in RCT PERFECT Phase 3.

Background: Bone marrow stem cell clonal dysfunction by somatic mutation is suspected to affect post-infarction myocardial regeneration after coronary bypass surgery (CABG).

Methods: Transcriptome and variant expression analysis was studied in the phase 3 PERFECT trial post myocardial infarction CABG and CD133 bone marrow derived hematopoetic stem cells showing difference in left ventricular ejection fraction (∆LVEF) myocardial regeneration Responders (n=14; ∆LVEF +16% day 180/0) and Non-responders (n=9; ∆LVEF -1.1% day 180/0).

Local transplantation of adipose-derived stem cells has a significant therapeutic effect in a mouse model of rheumatoid arthritis.

Adipose-derived stem cells (ADSCs) have anti-inflammatory and regenerative properties. The purpose of this study was to investigate the effect of locally administered ADSCs in a rheumatoid arthritis (RA) mouse model. In an in vivo experiment, single-cell ADSCs and three dimensionally-cultured ADSC spheroids were injected intra-articularly into the knees of RA model mice and histologically assessed.

Cardiac Regeneration by Statin-Polymer Nanoparticle-Loaded Adipose-Derived Stem Cell Therapy in Myocardial Infarction.

Clinical trials with autologous adipose-derived stem cell (AdSC) therapy for ischemic heart diseases (IHDs) are ongoing. However, little is known about combinational therapeutic effect of AdSCs and statin poly(lactic-co-glycolic) acid (PLGA) nanoparticles on the ischemic myocardium. We investigated the hypothesis that statins, which have pleiotropic effects, augment the therapeutic potential of AdSCs and that AdSCs also act as drug delivery tools.

Sufficient therapeutic effect of cryopreserved frozen adipose-derived regenerative cells on burn wounds.

Introduction: The purpose of this study was to evaluate whether cryopreserved (frozen) adipose-derived regenerative cells (ADRCs) have a therapeutic effect on burn wound healing as well as freshly isolated (fresh) ADRCs.

Methods: Full thickness burns were created on dorsum of nude mice and burn wound was excised. The wound was covered by artificial dermis with; (i) fresh ADRCs, (ii) frozen ADRCs, and (iii) PBS (control).

Establishment of a novel mouse xenograft model of human uterine leiomyoma.

Uterine leiomyoma is the most common benign tumour in women, and an appropriate animal model for leiomyoma would be useful for exploring new therapeutic strategies. Therefore, we have been challenged to develop a new simple mouse model for human leiomyoma. Leiomyoma tissues were harvested from myomas resected by different surgical procedures with or without gonadotropin-releasing hormone agonist (GnRHa) treatment and were subcutaneously implanted into BALB/c nude mice with an estradiol/progesterone-releasing pellet.

Publisher Correction: Anti-inflammatory and anti-fibrotic effects of intravenous adipose-derived stem cell transplantation in a mouse model of bleomycin-induced interstitial pneumonia.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Publisher Correction: Anti-inflammatory and anti-fibrotic effects of intravenous adipose-derived stem cell transplantation in a mouse model of bleomycin-induced interstitial pneumonia.

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

W9 peptide enhanced osteogenic differentiation of human adipose-derived stem cells.

W9 is a peptide that abrogates osteoclast differentiation via blockade of nuclear factor-κB ligand (RANKL)-RANK signaling, which activates bone formation. However, W9 stimulated osteogenesis in osteoblasts and mesenchymal stem cells. The present study demonstrated that the W9 peptide promoted osteogenic differentiation of human adipose-derived stem cells (hAdSCs) even under non-osteogenic differentiation culture conditions.

Anti-inflammatory and anti-fibrotic effects of intravenous adipose-derived stem cell transplantation in a mouse model of bleomycin-induced interstitial pneumonia.

Adipose-derived stem cells (AdSCs) have recently been considered a useful treatment tool for autoimmune disease because of their anti-inflammatory and immunosuppressive effects. We investigated the therapeutic effect of intravenous AdSC transplantation in a mouse model of bleomycin-induced lung injury. AdSCs accumulated in the pulmonary interstitium and inhibited both inflammation and fibrosis in the lung, markedly improving the survival rate of mice with bleomycin-induced lung injury in a cell number-dependent manner.

Curcumin induces therapeutic angiogenesis in a diabetic mouse hindlimb ischemia model via modulating the function of endothelial progenitor cells.

Background: Neovascularization is impaired in diabetes mellitus, which leads to the development of peripheral arterial disease and is mainly attributed to the dysfunction of endothelial progenitor cells (EPCs). Previous studies proved the promotional effect of curcumin on neovascularization in wound healing of diabetes. Thus, we hypothesize that curcumin could promote neovascularization at sites of hindlimb ischemia in diabetes and might take effect via modulating the function of EPCs.

Rosuvastatin as a potential preventive drug for the development of hepatocellular carcinoma associated with non-alcoholic fatty liver disease in mice.

Hepatocellular carcinoma (HCC) represents approximately 85% of all primary liver cancer cases. Non-alcoholic fatty liver disease (NAFLD) is one of the risk factors for HCC. NAFLD occurs in patients with components of metabolic syndrome, such as type 2 diabetes mellitus, obesity, hypertension and hyperlipidemia.

Regulatory roles of interferon-inducible protein 204 on differentiation and vasculogenic activity of endothelial progenitor cells.

Background: Endothelial progenitor cells (EPCs) have shown great potential in angiogenesis either by their differentiation into endothelial cells or by secretion of angiogenic factors. Interferon-inducible protein 204 (Ifi204) has been reported to participate in the regulation of cell growth and differentiation. However, its role in differentiation of EPCs remains unknown.

Bone Marrow-Derived Endothelial Progenitor Cells Reduce Recurrent Miscarriage in Gestation.

Bone marrow-derived endothelial progenitor cells (EPCs) have been shown to contribute to not only angiogenesis in ischemic tissue but also neovascularization in uterine endometrium formation. Reduced neovascularization and elevation of serum soluble Flt1, a functional blockage of VEGF, in the development of placenta is thought to be one of the major causes of repeated miscarriages in gestation. We then examined whether transfusion of VEGF-expressing extrinsic EPCs prevented frequent miscarriage via its promotional effect on neovascularization with a VEGFeNOS signaling pathway in a mouse miscarriage model.

microRNA-145 Mediates the Inhibitory Effect of Adipose Tissue-Derived Stromal Cells on Prostate Cancer.

Adipose-derived stromal cell (ASC), known as one of the mesenchymal stem cells (MSCs), is a promising tool for regenerative medicine; however, the effect of ASCs on tumor growth has not been studied sufficiently. We investigated the hypothesis that ASCs have an inhibitory effect on metastatic tumor progression. To evaluate the in vitro inhibitory effect of ASCs on metastatic prostate cancer (PCa), direct coculture and indirect separate culture experiments with PC3M-luc2 cells and human ASCs were performed, and ASCs were administered to PC3M-luc2 cell-derived tumor-bearing nude mice for in vivo experiment.

Ex vivo expansion of circulating CD34(+) cells enhances the regenerative effect on rat liver cirrhosis.

Ex vivo expansion of autologous cells is indispensable for cell transplantation therapy of patients with liver cirrhosis. The aim of this study was to investigate the efficacy of human ex vivo-expanded CD34(+) cells for treatment of cirrhotic rat liver. Recipient rats were intraperitoneally injected with CCl4 twice weekly for 3 weeks before administration of CD34(+) cells.

Cardiac Adipose-Derived Stem Cells Exhibit High Differentiation Potential to Cardiovascular Cells in C57BL/6 Mice.

Adipose-derived stem cells (AdSCs) have recently been shown to differentiate into cardiovascular lineage cells. However, little is known about the fat tissue origin-dependent differences in AdSC function and differentiation potential. AdSC-rich cells were isolated from subcutaneous, visceral, cardiac (CA), and subscapular adipose tissue from mice and their characteristics analyzed.

Mesenchymal stem cells preconditioned with trimetazidine promote neovascularization of hearts under hypoxia/reoxygenation injury.

Background: Cell-based angiogenesis is a promising treatment for ischemic diseases; however, survival of implanted cells is impaired by the ischemic microenvironment. In this study, mesenchymal stem cells (MSCs) for cell transplantation were preconditioned with trimetazidine (TMZ). We hypothesized that TMZ enhances the survival rate of MSCs under hypoxic stimuli through up-regulation of HIF1-α.

Sitagliptin can inhibit the development of hepatic steatosis in high-fructose diet-fed ob/ob mice.

The beneficial effect of dipeptidyl peptidase-4 inhibition on diet-induced extra-pancreatic effects, especially on liver tissue remains poorly understood. Thus, we made the experimental designs as follows; five-week-old male ob/ob mice, which develop type 2 diabetic mellitus and nonalcoholic fatty liver disease by taking a high-carbohydrate diet (HCD), were divided into a group in which a HCD was given for 8 weeks as control, and another in which a HCD added with 0.0018% sitagliptin was given for 8 weeks.

Preoperative ejection fraction determines early recovery of left ventricular end-diastolic dimension after aortic valve replacement for chronic severe aortic regurgitation.

Background: In patients with chronic severe aortic regurgitation (AR), aortic valve replacement (AVR) has been proved to promote left ventricular (LV) remodeling, especially LV end-diastolic dimension (LVEDD) reduction. However, there is little research whether postoperative LVEDD could return to normal parameter after AVR. The objective of this study was to determine predictors for the recovery of dilated LVEDD early after AVR.

Sonic Hedgehog signaling regulates vascular differentiation and function in human CD34 positive cells: vasculogenic CD34(+) cells with Sonic Hedgehog.

Identification of pivotal factors potentially present in the in situ environment and capable of influencing the function of CD34(+) cells, which can be used for autologous cell therapy, is of paramount interest. SHh is one of the morphogens essential for embryonic vascular development as well as postnatal neovascularization, and the activation of SHh signaling with angiogenic and vascular differentiation responses in CD34(+) cells by SHh treatment differed depending on the G-CSF treatment or the background disease. SHh enhanced the migration, proliferation, adhesion, and EPC colony forming capacities of G-CSF mobilized CD34(+) cells, increasing the vasculogenic/angiogenic potential for neovascularization.

A vascular patch prepared from Thai silk fibroin and gelatin hydrogel incorporating simvastatin-micelles to recruit endothelial progenitor cells.

Delayed re-endothelialization is one of the major disadvantages in synthetic vascular grafts, especially in small-diameter grafts (inner diameter <6 mm), leading to thrombosis and stenosis of the grafts. Simvastatin, a serum cholesterol-lowering drug, has promotional effects on endothelial progenitor cell (EPC) mobilization from bone marrow and recruitment to sites of vascular injury exhibiting acceleration of re-endothelialization. In this study, we prepared double-layer vascular patches from Thai silk fibroin/gelatin with gelatin hydrogel incorporating simvastatin-micelles (SM) for sustained release of simvastatin to recruit circulation EPCs.

SDF-1/CXCR4 axis in Tie2-lineage cells including endothelial progenitor cells contributes to bone fracture healing.

CXC chemokine receptor 4 (CXCR4) is a specific receptor for stromal-derived-factor 1 (SDF-1). SDF-1/CXCR4 interaction is reported to play an important role in vascular development. On the other hand, the therapeutic potential of endothelial progenitor cells (EPCs) in fracture healing has been demonstrated with mechanistic insight of vasculogenesis/angiogenesis and osteogenesis enhancement at sites of fracture.

Superior Potential of CD34-Positive Cells Compared to Total Mononuclear Cells for Healing of Nonunion Following Bone Fracture.

We recently demonstrated that the local transplantation of human peripheral blood (PB) CD34(+) cells, an endothelial/hematopoietic progenitor cell-rich population, contributes to fracture repair via vasculogenesis/angiogenesis and osteogenesis. Human PB mononuclear cells (MNCs) are also considered a potential cell fraction for neovascularization. We have previously shown the feasibility of human PB MNCs to enhance fracture healing.