Enhanced bioactivity of transform growth factor-β1 from sulfated chitosan microspheres for in vitro chondrogenesis of mesenchymal stem cells

2014 ◽  
Vol 86 (12) ◽  
pp. 1885-1895 ◽  
Author(s):  
Feifei Li ◽  
Lie Ma ◽  
Bo Li ◽  
Changyou Gao
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
In Vitro Release ◽  
Transform Growth Factor ◽  
Blank Group ◽  
Chitosan Microspheres ◽  
Tgf Β1

Abstract Transform growth factor-β1 (TGF-β1) is an extremely powerful protein to induce the chondrogenesis of mesenchymal stem cells (MSCs) both in vitro and in vivo. However, due to the short-life of TGF-β1, the direct application of TGF-β1 may deteriorate its bioactivity and thereby the repair effect. In this study, uniform sulfated chitosan microspheres (SCMs) with a mean diameter of ∼ 2 μm were fabricated by membrane emulsification as a carrier for TGF-β1. The in vitro release study showed that TGF-β1 could be sustainedly released from the microspheres up to 16 days. Under the protection of SCMs, about 13 % TGF-β1 was preserved even after stored for 14 days. The microspheres cytotoxicity was evaluated by coculture of MSCs with different concentrations SCMs and no obvious deterioration of cell viability was observed when the concentration of SCMs is lower than 2 μg/1.0 × 104 cells. In comparison with the blank group, the addition of TGF-β1 either in free state or loaded in SCMs inhibited the proliferation trend of MSCs. Quantitative analysis of GAGs production and genes expression of COL II and aggrecan by qRT-PCR revealed that enhanced bioactivity of TGF-β1 was obtained in the group of TGF-β1/SCMs, indicating that SCMs could be functioned as a promising carrier of TGF-β1 for the in vitro chondrogenesis of MSCs.

Combined Effects of Bone Marrow-Derived Mesenchymal Stem Cells and PLGA-PEG-PLGA Scaffolds on Repair of Articular Cartilage Defect

2013 ◽  
Vol 815 ◽  
pp. 345-349 ◽  
Author(s):  
Ching Wen Hsu ◽  
Ping Liu ◽  
Song Song Zhu ◽  
Feng Deng ◽  
Bi Zhang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Growth Factor ◽  
Cartilage Defect ◽  
Cartilage Regeneration ◽  
Tissue Growth ◽  
Cartilage Defects

Here we reported a combined technique for articular cartilage repair, consisting of bone arrow mesenchymal stem cells (BMMSCs) and poly (dl-lactide-co-glycolide-b-ethylene glycol-b-dl-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymers carried with tissue growth factor (TGF-belat1). In the present study, BMMSCs seeded on PLGA-PEG-PLGA with were incubated in vitro, carried or not TGF-belta1, Then the effects of the composite on repair of cartilage defect were evaluated in rabbit knee joints in vivo. Full-thickness cartilage defects (diameter: 5 mm; depth: 3 mm) in the patellar groove were either left empty (n=18), implanted with BMMSCs/PLGA (n=18), TGF-belta1 modified BMMSCs/PLGA-PEG-PLGA. The defect area was examined grossly, histologically at 6, 24 weeks postoperatively. After implantation, the BMMSCs /PLGA-PEG-PLGA with TGF-belta1 group showed successful hyaline-like cartilage regeneration similar to normal cartilage, which was superior to the other groups using gross examination, qualitative and quantitative histology. These findings suggested that a combination of BMMSCs/PLGA-PEG-PLGA carried with tissue growth factor (TGF-belat1) may be an alternative treatment for large osteochondral defects in high loading sites.

Hypoxia promotes tenocyte differentiation of mesenchymal stem cells

2020 ◽  
Author(s):  
Guanyin Chen ◽  
wangqian zhang ◽  
Jintao Gu ◽  
Yuan Gao ◽  
Lei He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Patellar Tendon ◽  
Tendon Repair ◽  
Clinical Results ◽  
Tendon Injury ◽  
Tenogenic Differentiation ◽  
Tgf Β1

Abstract Background: Tendon injury is a common but tough medical problem. Unsatisfactory clinical results have been reported in tendon repair using mesenchymal stem cells (MSCs) therapy, creating a need for a better strategy to induce MSCs to tenogenic differentiation. This study was designed to investigate the role of hypoxia in the tenogenic differentiation of MSCs in vitro and in vivo and to compare the tenogenic differentiation capacities of different MSCs under hypoxia condition in vitro. Methods: Adipose tissue-derived MSCs (AMSCs) and bone marrow-derived MSCs (BMSCs) were isolated and characterized by the expression of MSC-specific markers and tri-lineage differentiation. The expression of hypoxia induced factor-1 alpha (Hif-1α) and the proliferation of AMSCs and BMSCs were examined in order to confirm the establishment of hypoxia condition. qRT-PCR, western blot, and immunofluorescence staining were used to evaluate the expression of tendon-associated marker Col-1a1, Col-3a1, Dcn, and Tnmd in AMSCs and BMSCs under hypoxia and/or Tgf-β1 condition. In vivo, a patellar tendon injury model was established. Normoxic and hypoxic BMSCs were cultured and implanted. Histological, biomechanical and transmission electron microscopy analyses were performed to assess the improved healing effect of hypoxic BMSCs on tendon injury. Results: Hypoxia remarkably increased the expression of Hif-1α and the proliferation of AMSCs and BMSCs. Our in vitro results detected that hypoxia not only promoted a significant increase in tenogenic markers in both AMSCs and BMSCs compared with the normoxia group, but also showed higher inductility compared with Tgf-β1. In addition, hypoxic BMSCs exhibited higher potential of tenogenic differentiation than hypoxic AMSCs. Our in vivo results demonstrated that hypoxic BMSCs possessed better histological and biomechanical properties than those of normoxic BMSCs, as evidenced by histological scores, quantitative analysis of immunohistochemical staining for Col-1a1 and Tnmd, the range and average of collagen fibril diameters and patellar tendon biomechanical tests. Conclusions: These findings suggested that hypoxia may be a practical and reliable strategy to induce tenogenic differentiation of BMSCs for tendon repair and could enhance the effectiveness of MSCs therapy in treating tendon injury.

scholarly journals Mesenchymal Stem Cells Desensitize Castration-resistant Prostate Cancer to Docetaxel Chemotherapy via Inducing TGF-β1-mediated Cell Autophagy

2020 ◽  
Author(s):  
Yang Yu ◽  
Wen-tao Zhang ◽  
Fu-han Yang ◽  
Ya-dong Guo ◽  
Lin Ye ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Docetaxel Chemotherapy ◽  
Tgf Β1

Abstract Background: Mesenchymal stem cells (MSCs) have been proved to accelerate prostate cancer (PCa) castration resistance progression. The purpose of this study is to investigate the contribution of MSCs to the development of docetaxel resistance in castration-resistant prostate cancer (CRPC) cells and its potential mechanisms.Methods: The effect of MSCs on CRPC cells resistance to docetaxel was determined using in-vivo and in-vitro approaches. CCK8 and PI/Annexin V-FITC assay were used to examined the cell viability and apoptosis. The concentration of transforming growth factor-β1 was measured by enzyme-linked immunosorbent assay and small interfering RNA was used for functional analyses.Results: MSCs significantly reduced the sensitivity of CRPC cells to docetaxel-induced proliferation inhibition and apoptosis promotion in vivo and in vitro. CRPC cells cocultured with MSCs under docetaxel administration have an increased autophagy activation, while autophagy inhibitor could effectively reversed MSCs-induced resistance to docetaxel. Additionally, MSCs-induced CRPC cell autophagy increase under docetaxel administration depends on MSCs secreting TGF-β1 and inhibition of TGF-β1 secretion in MSCs could consequently increase the sensitivity of CRPC cells to docetaxel.Conclusions: These results suggest that docetaxel administrated CRPC cells may elicit MSCs secreting TGF-β1 increase, which desensitizes CRPC to docetaxel chemotherapy accelerating chemoresistance occurrence via inducing cell autophagy.

scholarly journals Biocompatible PLGA-Mesoporous Silicon Microspheres for the Controlled Release of BMP-2 for Bone Augmentation

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 118 ◽  
Author(s):  
Silvia Minardi ◽  
Joseph S. Fernandez-Moure ◽  
Dongmei Fan ◽  
Matthew B. Murphy ◽  
Iman K. Yazdi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Sustained Release ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Bone Morphogenetic Protein 2 ◽  
Osteogenic Potential ◽  
Bone Augmentation

Bone morphogenetic protein-2 (BMP-2) has been demonstrated to be one of the most vital osteogenic factors for bone augmentation. However, its uncontrolled administration has been associated with catastrophic side effects, which compromised its clinical use. To overcome these limitations, we aimed at developing a safer controlled and sustained release of BMP-2, utilizing poly(lactic-co-glycolic acid)-multistage vector composite microspheres (PLGA-MSV). The loading and release of BMP-2 from PLGA-MSV and its osteogenic potential in vitro and in vivo was evaluated. BMP-2 in vitro release kinetics was assessed by ELISA assay. It was found that PLGA-MSV achieved a longer and sustained release of BMP-2. Cell cytotoxicity and differentiation were evaluated in vitro by MTT and alkaline phosphatase (ALP) activity assays, respectively, with rat mesenchymal stem cells. The MTT results confirmed that PLGA-MSVs were not toxic to cells. ALP test demonstrated that the bioactivity of BMP-2 released from the PLGA-MSV was preserved, as it allowed for the osteogenic differentiation of rat mesenchymal stem cells, in vitro. The biocompatible, biodegradable, and osteogenic PLGA-MSVs system could be an ideal candidate for the safe use of BMP-2 in orthopedic tissue engineering applications.

scholarly journals Mesenchymal stem cells desensitize castration-resistant prostate cancer to docetaxel chemotherapy via inducing TGF-β1-mediated cell autophagy

2020 ◽  
Author(s):  
Yang Yu ◽  
Wen-tao Zhang ◽  
Fu-han Yang ◽  
Ya-dong Guo ◽  
Lin Ye ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Docetaxel Chemotherapy ◽  
Tgf Β1

Abstract Background: Mesenchymal stem cells (MSCs) have been proved to accelerate prostate cancer (PCa) castration resistance progression. The purpose of this study is to investigate the contribution of MSCs to the development of docetaxel resistance in castration-resistant prostate cancer (CRPC) cells and its potential mechanisms. Methods: The effect of MSCs on CRPC cells resistance to docetaxel was determined using in-vivo and in-vitro approaches. CCK8 and PI/Annexin V-FITC assay were used to examined the cell viability and apoptosis. The concentration of transforming growth factor-β1 was measured by enzyme-linked immunosorbent assay and small interfering RNA was used for functional analyses. Results: MSCs significantly reduced the sensitivity of CRPC cells to docetaxel-induced proliferation inhibition and apoptosis promotion in vivo and in vitro. CRPC cells cocultured with MSCs under docetaxel administration have an increased autophagy activation, while autophagy inhibitor could effectively reversed MSCs-induced resistance to docetaxel. Additionally, MSCs-induced CRPC cell autophagy increase under docetaxel administration depends on MSCs secreting TGF-β1 and inhibition of TGF-β1 secretion in MSCs could consequently increase the sensitivity of CRPC cells to docetaxel. Conclusions: These results suggest that docetaxel administrated CRPC cells may elicit MSCs secreting TGF-β1 increase, which desensitizes CRPC to docetaxel chemotherapy accelerating chemoresistance occurrence via inducing cell autophagy.

EFFECTS OF SHORT-TERM CYCLIC HYDROSTATIC PRESSURE ON INITIATING AND ENHANCING THE EXPRESSION OF CHONDROGENIC GENES IN HUMAN ADIPOSE-DERIVED MESENCHYMAL STEM CELLS

2014 ◽  
Vol 14 (04) ◽  
pp. 1450054 ◽  
Author(s):  
FARZANEH SAFSHEKAN ◽  
MOHAMMAD TAFAZZOLI SHADPOUR ◽  
MOHAMMAD ALI SHOKRGOZAR ◽  
NOOSHIN HAGHIGHIPOUR ◽  
SEYED HAMED ALAVI
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Hydrostatic Pressure ◽  
Chondrogenic Differentiation ◽  
Negative Control ◽  
Cartilage Tissue ◽  
Control Group

Cartilage tissue engineering is a promising treatment for damaged or diseased cartilage that requires thorough understanding of influential parameters involved in chondrogenic differentiation. This study examined how 4-h application of cyclic hydrostatic pressure (CHP) of 5 MPa at 0.5 Hz could modulate chondroinduction of human adipose-derived mesenchymal stem cells (hAMSCs) in vitro. Four groups were examined including a negative control group, a chemical group treated by growth factor for 10 days, a mechanical group exposed to 4-h loading on the 10th day of pellet culture without any chondrogenic stimulator, and finally a chemical-mechanical group subjected to both growth factor and loading. Application of cyclic hydrostatic pressure increased the expression of chondrogenic genes, including sox9 and aggrecan to higher levels than those of the chemical group. This study indicates that cyclic hydrostatic pressure initiates and enhances the chondrogenic differentiation of mesenchymal stem cells with or without growth factors in vitro and confirms the important role of hydrostatic pressure during chondrogenesis in vivo.

The metastatic phenotype shift toward myofibroblast of adipose-derived mesenchymal stem cells promotes ovarian cancer progression

2019 ◽  
Vol 41 (2) ◽  
pp. 182-193 ◽  
Author(s):  
Huijuan Tang ◽  
Yijing Chu ◽  
Zaiju Huang ◽  
Jing Cai ◽  
Zehua Wang
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cancer Metastasis ◽  
Abdominal Cavity ◽  
Ovarian Cancer Cells ◽  
Proliferation And Invasion ◽  
Tgf Β1

Abstract Ovarian cancer metastasizes to organs in the abdominal cavity, such as the omentum that is a rich source of adipose-derived mesenchymal stem cells (ADSCs). In present, ADSCs have received more and more attention for their roles in the development of cancer. In this study, we examined α-smooth muscle actin (α-SMA) expression and carcinoma-associated fibroblast (CAF)-like differentiation capabilities in ADSCs from omentum of different patients. The effects of ADSCs on the proliferation and invasion of epithelial ovarian cancer cells (EOCCs) were also assessed in vitro and in vivo. Our results showed that ADSCs from omentum of ovarian cancer patients, no matter whether metastasis or not, expressed higher levels of α-SMA than ADSCs from patients with benign gynecologic disease. Using direct and indirect co-culture system, we found that EOCCs induced ADSCs to express CAF markers, including α-SMA and fibroblast activation protein, via the transforming growth factor beta 1 (TGF-β1) signaling pathway. Moreover, co-cultured ADSCs exhibited functional properties similar to those of CAFs, including the ability to promote EOCCs proliferation, progression and metastasis both in vitro and in vivo. Furthermore, blocking the TGF-β1 pathway can counteract the CAF-like differentiation and tumor promotion effect of ADSCs. Our results suggest that ADSCs are a source of CAFs and that they participate in the interaction between EOCCs and the omental microenvironment. EOCCs could induce ADSCs in the omentum to differentiate before ovarian cancer metastasis, which participate in the formation of omental metastatic niches and promote the proliferation and invasion of ovarian cancer.

scholarly journals Mesenchymal stem cells desensitize castration-resistant prostate cancer to docetaxel chemotherapy via inducing TGF-β1-mediated cell autophagy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yang Yu ◽  
Fu-han Yang ◽  
Wen-tao Zhang ◽  
Ya-dong Guo ◽  
Lin Ye ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Docetaxel Chemotherapy ◽  
Tgf Β1

Abstract Background Mesenchymal stem cells (MSCs) have been proved to drive castration resistant prostate cancer (CRPC). In this study, we aim to investigate the contribution of MSCs to the development of docetaxel resistance in CRPC cells and its potential mechanisms. Methods The effect of MSCs on CRPC cells resistance to docetaxel was determined using in vivo and in vitro approaches. CCK8 and PI/Annexin V-FITC assay were used to examined the cell viability and apoptosis. The concentration of transforming growth factor-β1 was measured by enzyme-linked immunosorbent assay and small interfering RNA was used for functional analyses. Results MSCs significantly reduced the sensitivity of CRPC cells to docetaxel-induced proliferation inhibition and apoptosis promotion in vivo and in vitro. CRPC cells cocultured with MSCs under docetaxel administration have an increased autophagy activation, while autophagy inhibitor could effectively reversed MSCs-induced resistance to docetaxel. Additionally, MSCs-induced CRPC cell autophagy increase under docetaxel administration depends on MSCs secreting TGF-β1 and inhibition of TGF-β1 secretion in MSCs could consequently increase the sensitivity of CRPC cells to docetaxel. Conclusions These results suggest that docetaxel administrated CRPC cells may elicit MSCs secreting TGF-β1 increase, which desensitizes CRPC to docetaxel chemotherapy accelerating chemoresistance occurrence via inducing cell autophagy.

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