Adipose-derived stem cells (ADSCs) are pluripotent stem cells isolated from the adipose tissue and have the potential for self-renewal and multi-directional differentiation into neurogenic cells, smooth muscle cells, endothelial cells, and so on. Erectile dysfunction (ED) is a common male sexual dysfunction that has a negative impact on the lives of the patients and their partners. Current treatments of ED include surgery and medication, with oral 5-phosphodiesterase inhibitors as the first-line drugs. However, a small number of the patients are not sensitive to these therapies and cannot be improved or cured pathologically. So far, animal experiments and preclinical trials have confirmed the safety and efficacy of ADSCs, which act on ED though paracrine mechanisms. This review summarizes the advances in the recent 5 years in the studies of ADSCs for the treatment of ED.
Adipocytes ; transplantation ; Adipose Tissue ; cytology ; Animals ; Cell Differentiation ; Erectile Dysfunction ; surgery ; Humans ; Male ; Stem Cell Transplantation ; methods ; trends

Regenerative medicine is an emerging discipline. Adipose tissue is a rich source of fat cells and mesenchymal stem cells, and autologous fat grafting has increasingly been applied in plastic surgeries and dermatological treatments. This paper reviews the latest advances in autologous fat grafting in scar revision.
Adipocytes ; transplantation ; Adipose Tissue ; cytology ; Cicatrix ; surgery ; Humans ; Mesenchymal Stem Cell Transplantation ; Reconstructive Surgical Procedures

Adipocytes ; cytology ; Humans ; Stem Cell Transplantation ; methods ; Stroke ; therapy

Traditional adipose tissue transplantation has unpredictable viability and poor absorption rates. Recent studies have reported that treatment with platelet-rich plasma (PRP), adipose-derived stem cells (ASCs), and stromal vascular fraction (SVF) are related to increased survival of grafted adipose tissue. This study was the first simultaneous comparison of graft survival in combination with PRP, ASCs, and SVF. Adipose tissues were mixed with each other, injected subcutaneously into the back of nude mice, and evaluated at 4, 8, and 12 weeks. Human adipocytes were grossly maintained in the ASCs and SVF mixtures. Survival of the adipose tissues with PRP was observed at 4 weeks and with SVF at 8 and 12 weeks. At 12 weeks, volume reduction in the ASCs and SVF mixtures were 36.9% and 32.1%, respectively, which were significantly different from that of the control group without adjuvant treatment, 51.0%. Neovascular structures were rarely observed in any of the groups. Our results suggest that the technique of adding ASCs or SVF to transplanted adipose tissue might be more effective than the conventional grafting method. An autologous adipose tissue graft in combination with ASCs or SVF may potentially contribute to stabilization of engraftment.
Adipocytes/*transplantation ; Adipose Tissue/cytology/*transplantation ; Adult ; Animals ; Female ; *Graft Survival ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; *Platelet-Rich Plasma ; Stem Cells ; Stromal Cells/*transplantation ; Transplantation, Heterologous

Soft tissue augmentation is a process of implanting tissues or materials to treat wrinkles or soft tissue defects in the body. Over the years, various materials have evolved to correct soft tissue defects, including a number of tissues and polymers. Autogenous dermis, autogenous fat, autogenous dermis-fat, allogenic dermis, synthetic implants, and fillers have been widely accepted for soft tissue augmentations. Tissue engineering technology has also been introduced and opened a new venue of opportunities in this field. In particular, a long-lasting filler consisting of hyaluronic acid filler and living human mesenchymal cells called "injectable tissue-engineered soft tissue" has been created and applied clinically, as this strategy has many advantages over conventional methods. Fibroblasts and adipose-derived stromal vascular fraction cells can be clinically used as injectable tissue-engineered soft tissue at present. In this review, information on the soft tissue augmentation method using the injectable tissue-engineered soft tissue is provided.
Adipocytes/transplantation ; Adipose Tissue/cytology ; Biocompatible Materials ; Connective Tissue/*surgery ; Dermatologic Surgical Procedures/*methods ; Face ; Fibroblasts/transplantation ; Humans ; Hyaluronic Acid/therapeutic use ; Injections, Intradermal ; Mesenchymal Stem Cell Transplantation/*methods ; Mesenchymal Stromal Cells ; Skin ; Skin Aging ; Tissue Engineering/*methods

When mature adipocytes are subjected to an in vitro dedifferentiation strategy referred to as ceiling culture, these mature adipocytes can revert to dedifferentiated fat (DFAT) cells. DFAT cells have many advantages compared with adipose-derived stem cells (ASCs) and bone marrow mesenchymal stem cells (BMSCs). For example, DFAT cells are homogeneous and could be obtained from donors regardless of their age. Furthermore, DFAT cells also have the same multi-lineage potentials and low immunogenicity as ASCs. As an excellent source of seed cells for tissue engineering and stem cell transplantation, DFAT cells have better prospects in the treatment of many clinical diseases, such as bone defects, neurological diseases, ischemic heart disease and kidney disease. It is necessary to make more intensive studies of DFAT cells. This article summarizes progresses in the immunological characteristics, differentiation ability and potential clinical applications of DFAT cells.
Adipocytes ; cytology ; Cell Dedifferentiation ; Cell Differentiation ; Cells, Cultured ; Humans ; Stem Cell Transplantation ; Tissue Engineering

OBJECTIVETo investigate the effects of allogeneic adipose-derived stem cells (ADSCs) of rat on the early neovascularization of autologous fat transplantation.

METHODS(1) Experiment 1. Adipose tissue was collected from both inguinal regions of two SD rats to isolate, culture, and purify ADSCs through collagen enzyme digestion, density gradient centrifugation, and adherence method. The fourth passage of cells were collected for morphologic observation, detection of expressions of surface markers CD34, CD49d, CD106, and CD45 of ADSCs with flow cytometer, identification of adipogenic and osteogenic differentiation, and determination of the cell proliferation ability with thiazolyl blue method. (2) Experiment 2. Another 30 SD rats were divided into allogeneic adipose granule (AG) group (A, n = 6), autologous AG group (B, n = 8), autologous ADSCs+autologous AG group (C, n = 8), and allogeneic ADSCs+autologous AG group (D, n = 8) according to the random number table. The fourth passage of ADSCs were obtained from adipose tissue from one side of inguinal region of SD rats in group C. Adipose tissue obtained from one side of inguinal region of SD rats of the other 3 groups was abandoned. The AG was prepared from another side of inguinal region of SD rats in the 4 groups. The mixture of 0.6 g AG from one rat and 1 mL DMEM/F12 nutrient solution was injected subcutaneously into the back of another rat in group A, and so on. Autologous AG was injected into its own body of the rats in group B. The mixture of 1 mL autologous ADSCs mixture which contains 3.0 × 10⁶ cells per mililitre autologous ADSCs combined with autologous AG was injected into the rats in group C. The mixture of 1 mL allogeneic ADSCs mixture which contains 3.0 × 10⁶ cells per mililitre ADSCs extractived from the former 2 rats in experiment 1 combined with autologous AG was injected into the rats in group D. At 7 days post transplantation, fat transplants were harvested for gross observation, measurement of wet weight, pathological observation, and assessment of cells with positive expression of CD31 with immunohistochemical method. Data were processed with one-way analysis of variance and SNK test.

RESULTS(1) The fourth passage of cells proliferated well showing fusiform shape similar to fibroblasts. These cells showed positive expression of CD34 and CD49d and weak positive expression of CD106 and CD45. They were able to differentiate into adipocytes and osteoblasts. These cells were identified as ADSCs. The fourth passage of cells grew faster than that of the tenth passage. (2) At 7 days post transplantation, no liquifying necrosis or infection was observed in the fat transplants of the rats in the 4 groups. Wet weight of the fat transplants in groups A and B was respectively (0.25 ± 0.04) and (0.26 ± 0.03) g, which were less than those of groups C and D [(0.36 ± 0.03) and (0.35 ± 0.04) g, with P values below 0.05]. HE staining showed that there were less fat cells and more fibroblasts in the transplants of group A, visible fibrous tissue around uneven shape of fat cells in the transplants of group B, and almost identical size and shape of fat cells and unobvious fibrous tissues were found in the transplants of groups C and D. The cells with positive expression of CD31 were distributed in fibrous tissues in larger number but less around fat cells in the transplants of group A, while more of these cells were observed surrounding fat cells in the transplants of group B. There were more cells with positive expression of CD31 distributed surrounding fat cells in the transplants of groups C and D than that in group B. The cells with positive expression of CD31 observed under 400 times field were more in number in groups C (20.5 ± 1.1) and D (22.1 ± 1.0) than in groups A (8.0 ± 3.6) and B (10.9 ± 1.7), with P values below 0.05.

CONCLUSIONSAllogeneic ADSCs combined with autologous AG can significantly improve the early vascularization of fat transplantation as well as autologous ADSCs combined with autologous AG.

Adipocytes ; cytology ; transplantation ; Adipose Tissue ; blood supply ; cytology ; Animals ; Burns ; complications ; metabolism ; pathology ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Neovascularization, Physiologic ; physiology ; Osteogenesis ; Rats ; Stem Cell Transplantation ; Stem Cells ; cytology ; physiology ; Transplantation, Autologous ; Wound Healing ; physiology

OBJECTIVETo evaluate the efficacy of cyclosporine A-nanoparticles emulsion (CsA-NP) combined with adipose tissue-derived stem cells (ASCs)transplantation therapy for acute myocardial infarction (AMI) in a miniswine model.

METHODSCsA-NP emulsion was prepared by the high-pressure homogenization method. Models were performed by coronary angioplasty for percutaneous balloon occlusion of left anterior descending artery (LAD). A total of 17 miniswines survived after AMI were divided into four groups: control group (n=5), CsA-NP group (n=4), ASCs group (n=4), and CsA-NP+ASCs group (n=4). ASCs or saline were delivered by intracoronary injection one week after AMI.Before cell transplantation and 8 weeks after cell transplantation, delayed-enhanced magnetic resonance imaging (DE-MRI) was performed to evaluate cardiac function and viability. The infarcted myocardium and implanted cells were histologically studied.

RESULTSEight weeks after treatment, the left ventricular ejection fraction (LVEF)significantly increased in the CsA-NP+ASCs group when compared with the ASCs group [(53.6 ± 2.4)% vs. (48.3 ± 1.8)%, P<0.05]; meanwhile, the infarct size significantly decreased [(6.2 ± 1.7)cm(3) vs.(7.5 ± 0.6) cm(3), P<0.05] and the thickness of the ventricular wall significantly increased (P<0.05). Histology showed that the number of surviving cells increased nearly by three times in the CsA-NP+ASCs group, and the expressions of the cardiomyocyte specific markers (cTnT and α-actin) were detected. Histological samples also showed that CsA-NP+ASCs group reduced fibrotic tissue, and down-regulated the activation of Caspase-3.

CONCLUSIONThe CsA-NP+ASCs combination therapy can enhance the viability of ASCs by improving LVEF and preventing LV expansion, which may be explained that CsA-NP has the anti-apoptotic effect and can promote the survivals and proliferation of ASCs.

Adipocytes ; cytology ; Animals ; Caspase 3 ; metabolism ; Cyclosporine ; therapeutic use ; Disease Models, Animal ; Myocardial Infarction ; therapy ; Nanoparticles ; Random Allocation ; Stem Cell Transplantation ; Swine

OBJECTIVETo explore the method for the isolation, cultivation, and purification of adipose-derived stem cells (ADSCs) and examine the oncogenesis and homing of ADSCs to the liver in vivo.

METHODSADSCs were isolated from female mice by digestion with 0.075% collagenase I and the morphology of the isolated cells was observed with examination of the cell surface markers and cell cycle. BALB/c mice were injected with 1×10(6) ADSCs on the back to evaluate the oncogenesis of ADSCs or with 1×10(6) ADSCs stained with 5, 6-carboxyfluorescein diacetate-succinimidyl ester (CFSE) via the tail vein to examine the cell homing to the liver.

RESULTSThe isolated ADSCs highly expressed CD29 and CD44 and were negative for CD34, CD45, CD11b and CD14. Cell cycle distribution analysis showed cell percentages in G0/G1, S, and G2/M phases of 80.1%, 7.9%, and 12%, respectively. The ADSCs had a low immunogenicity and did not express CD40, CD80, CD86, MHCI, MHCII or PDL-1. After stimulation with IFN-γ, the expression of CD40, CD80 and PDL-1 were up-regulated slightly in the cells. Dorsal injection of the ADSCs did not result in any tumor formation within 1 month, and ADSCs injected via the tail vein showed cell homing to the liver.

CONCLUSIONMurine ADSCs can be isolated and expanded effectively by collagenase digestion and adherent culture. The isolated ADSCs can successfully reside in the liver after implantation, and thus may serve as a promising candidate cell in stem cell therapy of liver diseases.

Adipocytes ; cytology ; Animals ; Cell Culture Techniques ; Cell Differentiation ; Cell Movement ; Cells, Cultured ; Female ; Liver ; cytology ; Mesenchymal Stromal Cells ; cytology ; Mice ; Mice, Inbred BALB C ; Stem Cell Transplantation

Auto-transplantation of adipose tissue is commonly used for the treatment of tissue defects in plastic surgery. The survival of the transplanted adipose tissue is not always constant, and one of reasons is the accelerated apoptosis of the implanted preadipocytes. We have recently established highly homogeneous preadipocytes, named ccdPAs. The aim of the current study was to evaluate the regulation of the potency of platelet-rich plasma (PRP) on the apoptosis of ccdPAs in vitro. PRP stimulated the proliferation of the preadipocytes in a dose-dependent manner, and the stimulatory activity of 2% PRP was significantly higher than that of 2% FBS or 2% platelet-poor plasma (PPP). The presence of 2% PRP significantly inhibited serum starvation- or TNF-alpha/cycloheximide-induced apoptosis in comparison to 2% FBS or 2% PPP. DAPK1 and Bcl-2-interacting mediator of cell death (BIM) mRNAs were reduced in the preadipocytes cultured with 2% PRP in comparison to those cultured in 2% FBS. The gene expression levels were significantly higher in cells cultured without serum in comparison to cells cultured with 2% FBS, and the levels in the cells with 2% PRP were reduced to 5-10% of those in the cells without serum. These results indicated that ccdPAs exhibit anti-apoptotic activities, in addition to increased proliferation, when cultured in 2% PRP in comparison to the same concentration of FBS, and that this was accompanied with reduced levels of DAPK1 and BIM mRNA expression in in vitro culture. PRP may improve the outcome of transplantation of adipose tissue by enhancing the anti-apoptotic activities of the implanted preadipocytes.
Adipocytes/*cytology ; Adipose Tissue/cytology/metabolism ; Apoptosis/*physiology ; Apoptosis Regulatory Proteins/antagonists & inhibitors/metabolism ; Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors/metabolism ; Cell Culture Techniques/*methods ; *Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Gene Expression Regulation ; Humans ; Membrane Proteins/antagonists & inhibitors/metabolism ; *Platelet-Rich Plasma/metabolism/physiology ; Proto-Oncogene Proteins/antagonists & inhibitors/metabolism ; Tissue Transplantation