Roles of adipocytes and adipose-derived stem cells in the lipophilic metastasis of ovarian cancer / 中国肿瘤临床

Ovarian cancer is the most common cause of cancer-associated deaths among the gynecological malignancies. The 5-year survival rate of the patients is less than 30%. This high mortality rate is mainly due to the metastasis. Adipose-rich omentum is the main site of metastasis, suggesting that ovarian cancer may have the characteristic of "lipophilic" metastasis. Adipocytes and adipose-derived stem cells are the most important components of the omentum. These cell ssecrete cytokines and adipokines and modify glucose and lipid metabolism to induce migration of ovarian cancer cells to the omentum. Simultaneously, they create a suitable microenvironment for the metastasis and colonization of these cancer cells by interacting with vascular endothelial cells, tumor-associated macrophages, and cancer-associated fibroblasts. This article reviews the recent advances in the role of adipocytes and adipose-derived stem cells in the "lipophilic" metastasis of ovarian cancer, aiming at providing new ideas for preventing ovarian cancer metastases and improving the survival rate of patients with ovarian cancer.

Research progress in immunoregulatory effects of adipose mesenchymal stem cells / 中华微生物学和免疫学杂志

Adipose derived mesenchymal stromal cells (ADSC) are pluripotent stem cells isolated from adipose tissue and have great application potential in regenerative medicine for their rich sources of derivation, relatively less trauma when sampling and few ethical problems. ADSC have preferable immunomodulatory capacity, and can regulate the immunologic functions of dendritic cells, macrophages, NK cells, NKT cells, B lymphocytes and T lymphocytes. In order to better understand the role of ADSC in immunoregulation, this paper systematically reviewed the immunomodulatory effects of ADSC on several representative immune cells.

Research progress in immunoregulatory effects of adipose mesenchymal stem cells / 中华微生物学和免疫学杂志

Adipose derived mesenchymal stromal cells (ADSC) are pluripotent stem cells isolated from adipose tissue and have great application potential in regenerative medicine for their rich sources of derivation, relatively less trauma when sampling and few ethical problems. ADSC have preferable immunomodulatory capacity, and can regulate the immunologic functions of dendritic cells, macrophages, NK cells, NKT cells, B lymphocytes and T lymphocytes. In order to better understand the role of ADSC in immunoregulation, this paper systematically reviewed the immunomodulatory effects of ADSC on several representative immune cells.

Adipose-Derived Stem Cell Transplantation Inhibits Vascular Inflammatory Responses and Endothelial Dysfunction in Rats with Atherosclerosis

PURPOSE: This study aimed to investigate the effect of adipose-derived stem cell (ADSC) transplantation on atherosclerosis (AS) and its underlying mechanisms. MATERIALS AND METHODS: In our study, rat AS model was established, and ADSCs were isolated and cultured. Atherosclerotic plaque and pathological symptoms of thoracic aorta were measured by Oil Red O staining and Hematoxylin-Eosin staining, respectively. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured by an automatic biochemical analyzer. Expressions of vascular endothelial growth factor (VEGF), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), aortic endothelin-1 (ET-1), interleukin-6 (IL-6), c-reactive protein (CRP), and tumor necrosis factor α (TNF-α) were measured by enzyme linked immunosorbent assay, VEGF, VCAM-1, ICAM-1, ET-1, respectively, and NF-κB p65 mRNA expressions were detected by quantitative real-time polymerase chain reaction. Protein expressions of VEGF, VCAM-1, ICAM-1, ET-1, NF-κB p65, p-NF-κB p65, and IκBα were measured by western blot. Moreover, NF-κB p65 expression was measured by immunofluorescence staining. RESULTS: ADSC transplantation alleviated the pathological symptoms of aortic AS. ADSC transplantation decreased the levels of TC, TG, and LDL-C and increased serum HDL-C level. Meanwhile, ADSC transplantation decreased the levels of IL-6, CRP, and TNF-α in AS rats. Moreover, the expressions of VEGF, ET-1, VCAM-1, and ICAM-1 were decreased by ADSC transplantation. ADSC transplantation inhibited phosphorylation of NF-κB p65 and promoted IκBα expression in AS rats. CONCLUSION: Our study demonstrated that ADSC transplantation could inhibit vascular inflammatory responses and endothelial dysfunction by suppressing NF-κB pathway in AS rats.

Expression patterns of mesenchymal stem cell-specific proteins in adipose tissue-derived cells: possible immunosuppressing agent in partial allograft for restoring the urinary bladder in rabbits / Padrão de expressão de proteínas específicas das células-tronco mesenquimais derivadas de tecido adiposo: possível agente imunossupressor em aloenxerto parcial para restauração de vesícula urinária de coelhos

Adipose tissue-derived stem cells (ADSCs) are an attractive source of mesenchymal stem cells (MSCs) for use in tissue engineering and clinical applications. This paper focuses on the characterization of ADSCs used as immunosuppressive agent in rabbits undergoing partial allograft for urine bladder restorage. For this study highlighted the characterization of the ADSCs used as immunosuppressive agents in rabbits submitted to partial allograft for restoration of the urinary vesicle, using 25 animals, six months old, New Zealand. ADSCs at the third peal were characterized by the MSC-specific CD105, CD73 and CD90 expression and by the absence of the hematopoietic marker CD45, as revealed by flow cytometry analysis. Moreover, ADSCs were efficient in preventing allograft rejection from the urinary bladder, as judged by biochemical, clinical and ultrasonography analysis. Together, these results compose characterization of protein expression profiles and immunosuppressive functionality of ADSCs in rabbits, which had undergone partial allografts of the urinary bladder, foreseeing future applications in clinical practice.(AU)

As células mesenquimais derivadas de tecido adiposo (ADSCs) são uma fonte atraente de células-tronco mesenquimais (MSCs) para uso na engenharia de tecidos e suas aplicações clínicas. Este trabalho destacou a caracterização das ADSCs utilizadas como agentes imunossupressores em coelhos submetidos a aloenxerto parcial para restauração da vesícula urinária, sendo utilizados 25 animais, de seis meses de idade, Nova Zelândia. As ADSCs, após o terceiro repique, foram caracterizadas pela expressão específica de MSC CD105, CD73 e CD90 e pela ausência do marcador hematopoiético CD45, tal como revelado por análise de citometria de fluxo. Além disso, os ADSCs foram eficientes na prevenção da rejeição de aloenxertos da vesícula urinária, conforme avaliado por análises clínica, bioquímica e ultrassonográfica. Juntos, esses resultados compõem a caracterização dos perfis de expressão proteica e a funcionalidade imunossupressora de ADSCs em coelhos, que sofreram aloenxertos parciais da bexiga, prevendo futuras aplicações na prática clínica.(AU)

Nanotechnology-assisted adipose-derived stem cell (ADSC) therapy for erectile dysfunction of cavernous nerve injury: In vivo cell tracking, optimized injection dosage, and functional evaluation / 亚洲男科学杂志(英文版)

Stem cell therapy is a potentially promising option for erectile dysfunction; however, its risk of tumorigenicity is a clinical hurdle and the risk is positively related to the number of injected cells. Our previous study showed that nanotechnology improved adipose-derived stem cell (ADSC) therapy for erectile dysfunction of cavernous nerve injury (CNI) by attracting cells in the corpus cavernosum. These results indicated the possibility of using a reduced dosage of ADSCs for intracavernous injection. In this exploratory study, we used lower dosage (2 × 105 cells) of ADSCs for intracavernous injection (ICI) and the nanotechnology approach. Intracavernous pressure and mean arterial pressure were measured at day 28 to assess erectile function. The low-dose ADSC therapy group showed favorable treatment effects, and nanotechnology further improved these effects. In vivo imaging of ICI cells revealed that the fluorescein signals of NanoShuttle-bound ADSCs (NanoADSCs) were much stronger than those of ADSCs at days 0, 1, and 3. Both immunofluorescence and Western blot analysis showed a significant increase in smooth muscle, endothelium, and nerve tissue in the ADSC group compared to that in the CNI group; further improvement was achieved with assisted nanotechnology. These findings demonstrate that nanotechnology can be used to further improve the effect of small dosage of ADSCs to improve erectile function. Abundant NanoADSCs remain in the corpus cavernosum in vivo for at least 3 days. The mechanism of erectile function improvement may be related to the regeneration of the smooth muscle, endothelium, and nerve tissues.

Nanotechnology-assisted adipose-derived stem cell (ADSC) therapy for erectile dysfunction of cavernous nerve injury: In vivo cell tracking, optimized injection dosage, and functional evaluation / 亚洲男科学杂志(英文版)

Stem cell therapy is a potentially promising option for erectile dysfunction; however, its risk of tumorigenicity is a clinical hurdle and the risk is positively related to the number of injected cells. Our previous study showed that nanotechnology improved adipose-derived stem cell (ADSC) therapy for erectile dysfunction of cavernous nerve injury (CNI) by attracting cells in the corpus cavernosum. These results indicated the possibility of using a reduced dosage of ADSCs for intracavernous injection. In this exploratory study, we used lower dosage (2 × 105 cells) of ADSCs for intracavernous injection (ICI) and the nanotechnology approach. Intracavernous pressure and mean arterial pressure were measured at day 28 to assess erectile function. The low-dose ADSC therapy group showed favorable treatment effects, and nanotechnology further improved these effects. In vivo imaging of ICI cells revealed that the fluorescein signals of NanoShuttle-bound ADSCs (NanoADSCs) were much stronger than those of ADSCs at days 0, 1, and 3. Both immunofluorescence and Western blot analysis showed a significant increase in smooth muscle, endothelium, and nerve tissue in the ADSC group compared to that in the CNI group; further improvement was achieved with assisted nanotechnology. These findings demonstrate that nanotechnology can be used to further improve the effect of small dosage of ADSCs to improve erectile function. Abundant NanoADSCs remain in the corpus cavernosum in vivo for at least 3 days. The mechanism of erectile function improvement may be related to the regeneration of the smooth muscle, endothelium, and nerve tissues.

Priming stem cells with protein kinase C activator enhances early stem cell-chondrocyte interaction by increasing adhesion molecules

BACKGROUND: Osteoarthritis (OA) can be defined as degradation of articular cartilage of the joint, and is the most common degenerative disease. To regenerate the damaged cartilage, different experimental approaches including stem cell therapy have been tried. One of the major limitations of stem cell therapy is the poor post-transplantation survival of the stem cells. Anoikis, where insufficient matrix support and adhesion to extracellular matrix causes apoptotic cell death, is one of the main causes of the low post-transplantation survival rate of stem cells. Therefore, enhancing the initial interaction of the transplanted stem cells with chondrocytes could improve the therapeutic efficacy of stem cell therapy for OA. Previously, protein kinase C activator phorbol 12-myristate 13-acetate (PMA)- induced increase of mesenchymal stem cell adhesion via activation of focal adhesion kinase (FAK) has been reported. In the present study, we examine the effect PMA on the adipose-derived stem cells (ADSCs) adhesion and spreading to culture substrates, and further on the initial interaction between ADSC and chondrocytes. RESULTS: PMA treatment increased the initial adhesion of ADSC to culture substrate and cellular spreading with increased expression of adhesion molecules, such as FAK, vinculin, talin, and paxillin, at both RNA and protein level. Priming of ADSC with PMA increased the number of ADSCs attached to confluent layer of cultured chondrocytes compared to that of untreated ADSCs at early time point (4 h after seeding). CONCLUSION: Taken together, the results of this study suggest that priming ADSCs with PMA can increase the initial interaction with chondrocytes, and this proof of concept can be used to develop a non-invasive therapeutic approach for treating OA. It may also accelerate the regeneration process so that it can relieve the accompanied pain faster in OA patients. Further in vivo studies examining the therapeutic effect of PMA pretreatment of ADSCs for articular cartilage damage are required.

Avaliações clínica, ecográfica e anatomofisiológica do alotransplante parcial de vesícula urinária com células-tronco mesenquimais alogênicas derivadas do tecido adiposo em coelhos / Clinical, sonographic, anatomic and physiological assessments of partial allotransplant urinary bladder with allogeneic mesenchymal stem cells derived from adipose tissue in rabbits

Os problemas relacionados ao armazenamento vesical são muitos e relevantes. Eles, além de influírem de forma efetiva na qualidade de vida, podem eventualmente evoluir para falência renal. Existem vários trabalhos, os quais descrevem as propriedades imunomoduladoras e imunossupressoras das células-tronco mesenquimais derivadas do tecido adiposo (ADSCs). Objetiva-se com o presente avaliar clínica, ecográfica e anatomofisiologicamente o alotransplante parcial de bexiga a fresco em coelhos, utilizando como agente imunomodulador ADSCs alogênicas. Para isso foram utilizados 25 coelhos, sendo um deles macho e doador das ADSCs, e os outros 24 eram fêmeas, submetidas a alotransplante parcial de bexiga, sendo tratadas com ciclosporina (GCi) ou células-tronco mesenquimais (GCe). Conclui-se que as ADSCs foram suficientes para evitar sinais clínicos e ecográficos de rejeição ao alotransplante de vesícula urinária, mantendo a estrutura anatomofisiológica vesical por até 30 dias em coelhos.

The problems related to bladder storage are many and significant. In addition to effectively impacting the quality of life, they can eventually progress to kidney failure. There are several studies which describe the immunomodulatory and immunosuppressive properties of ADSCs. The aim of this study is to clinically, through sonography, anatomically and physiologically evaluate fresh partial allograft bladder from rabbits using allogeneic ADSCs as immunomodulator agents. For such, 25 rabbits were used, one being a male ADSCs donor, and the other 24 females who underwent simultaneous partial allograft bladder, being treated with cyclosporine (GCi) or mesenchymal stem cells (GCe). It was concluded that ADSCs were sufficient to prevent clinical and ultrasound signs of allograft rejection of the urinary bladder. These bladders retained the anatomophysiological structure for 30 days in rabbits.

Effect of Murine Adipose Derived Stem Cell(ADSC) on Bone Induction of Demineralized Bone Matrix(DBM) in a Rat Calvarian Defect Model

PURPOSE: Adipose tissue-derived stem cells(ADSC) has an osteoconductive potential and demineralized bone matrix(DBM) is an osteoinductive material. A combination of DBM and ADSC wound probably create osteoinductive properties. The purpose of this study is to determine the effect of the combination of DBM and ADSC mixture on healing of rat calvarial defect. METHODS: Thirty adult male Sprague-Dawley rats were randomized into 3 groups(n=10) as 1) Control, 2) DBM alone, 3) DBM with ADSC mixture. DBM with ADSC mixture group has had a 3-day preculture of ADSC from groin fat pad. An 6 mm critical size circular calvarial defect was made in each rat. Defect was implanted with DBM alone or DBM with ADSC mixture. Control defect was left unfilled. 6 and 12 weeks after the implantation, the rats were sacrificed and the defects were evaluated by histomorphometric and radiographical studies. RESULTS: Histomorphometric analysis revealed that DBM with ADSC mixture group showed significantly higher bone formation than DBM alone group(p<0.05). Although radiographs from DBM alone group and DBM with ADSC group revealed similar diffuse radiopaque spots dispersed throughout the defect. Densitometric analysis of calvarial defect revealed DBM with ADSC mixture group significantly higher bone formation than DBM alone(p<0.05). There was correlation of densitometry with new bone formation(Spearman's correlation of coefficient=0.804, 6 weeks, 0.802, 12 weeks). CONCLUSION: The DBM with ADSC mixture group showed the best healing response and the osteoinductive properties of DBM were accelerated with ADSC mixture. It will be clinically applicable that DBM and ADSC mixture in plastic and reconstructive surgery, such as alveolar cleft and congenital facial deformities that bone graft should be required.