scholarly journals Methoxy-Poly(ethylene glycol) Modified Poly(L-lactide) Enhanced Cell Affinity of Human Bone Marrow Stromal Cells by the Upregulation of 1-Cadherin and Delta-2-catenin

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Xueli Mao ◽  
Zetao Chen ◽  
Junqi Ling ◽  
Jingjing Quan ◽  
Hui Peng ◽  
...  

Poly(l-lactide) (PLLA), a versatile biodegradable polymer, is one of the most commonly-used materials for tissue engineering applications. To improve cell affinity for PLLA, poly(ethylene glycol) (PEG) was used to develop diblock copolymers. Human bone marrow stromal cells (hBMSCs) were cultured on MPEG-b-PLLA copolymer films to determine the effects of modification on the attachment and proliferation of hBMSC. The mRNA expression of 84 human extracellular matrix (ECM) and adhesion molecules was analyzed using RT-qPCR to understand the underlying mechanisms. It was found that MPEG-b-PLLA copolymer films significantly improved cell adhesion, extension, and proliferation. This was found to be related to the significant upregulation of two adhesion genes, CDH1 and CTNND2, which encode 1-cadherin and delta-2-catenin, respectively, two key components for the cadherin-catenin complex. In summary, MPEG-b-PLLA copolymer surfaces improved initial cell adhesion by stimulation of adhesion molecule gene expression.

2004 ◽  
Vol 5 (1) ◽  
pp. 5-10 ◽  
Author(s):  
Johnna S. Temenoff ◽  
Hansoo Park ◽  
Esmaiel Jabbari ◽  
Daniel E. Conway ◽  
Tiffany L. Sheffield ◽  
...  

Nanomaterials ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 855 ◽  
Author(s):  
Weikun Meng ◽  
Ana Rey-Rico ◽  
Mickaël Claudel ◽  
Gertrud Schmitt ◽  
Susanne Speicher-Mentges ◽  
...  

Scaffold-assisted gene therapy is a highly promising tool to treat articular cartilage lesions upon direct delivery of chondrogenic candidate sequences. The goal of this study was to examine the feasibility and benefits of providing highly chondroreparative agents, the cartilage-specific sex-determining region Y-type high-mobility group 9 (SOX9) transcription factor or the transforming growth factor beta (TGF-β), to human bone marrow-derived mesenchymal stromal cells (hMSCs) via clinically adapted, independent recombinant adeno-associated virus (rAAV) vectors formulated with carbon dots (CDs), a novel class of carbon-dominated nanomaterials. Effective complexation and release of a reporter rAAV-lacZ vector was achieved using four different CDs elaborated from 1-citric acid and pentaethylenehexamine (CD-1); 2-citric acid, poly(ethylene glycol) monomethyl ether (MW 550 Da), and N,N-dimethylethylenediamine (CD-2); 3-citric acid, branched poly(ethylenimine) (MW 600 Da), and poly(ethylene glycol) monomethyl ether (MW 2 kDa) (CD-3); and 4-citric acid and branched poly(ethylenimine) (MW 600 Da) (CD-4), allowing for the genetic modification of hMSCs. Among the nanoparticles, CD-2 showed an optimal ability for rAAV delivery (up to 2.2-fold increase in lacZ expression relative to free vector treatment with 100% cell viability for at least 10 days, the longest time point examined). Administration of therapeutic (SOX9, TGF-β) rAAV vectors in hMSCs via CD-2 led to the effective overexpression of each independent transgene, promoting enhanced cell proliferation (TGF-β) and cartilage matrix deposition (glycosaminoglycans, type-II collagen) for at least 21 days relative to control treatments (CD-2 lacking rAAV or associated to rAAV-lacZ), while advantageously restricting undesirable type-I and -X collagen deposition. These results reveal the potential of CD-guided rAAV gene administration in hMSCs as safe, non-invasive systems for translational strategies to enhance cartilage repair.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5142-5142
Author(s):  
Akio Mori ◽  
Yutaka Tsutsumi ◽  
Satoshi Hashino ◽  
Hiroe Kanamori ◽  
Makoto Ibata ◽  
...  

Abstract Thalidomide (Thal) alone or in combination with steroids achieves responses even in the setting of refractory multiple myeloma (MM), however, responses are still limited. The precise mechanism of Thal action is unknown, further, no distinct marker, which could prognosticate the efficacy of Thal, is known. Therefore, we evaluated the correlation between the efficacy of Thal and the potent prognostic factors in patients with refractory MM. Ten patients with refractory MM received Thal at doses of 50 or 100 mg per day and steroids, either dexamethasone (Dex) or prednisolone (PSL). Dex was administrated 20 mg per day, 4 days every 28 days, and PSL was administrated 10 mg per day. The median age was 71.5 years (range, 62–79 years) and 20 % were man, and all patients were diagnosed as clinical stage IIIA based on the Durie and Salmon classification. The therapeutic response was assessed according to the modified criteria of Southwest Oncology Group (SWOG). Among 10 patients, 7 patients were the responders; 2 had complete remission, 3 had partial remission, and 2 had minimal remission. There were no differences in the pretreatment characteristics of responders and nonresponders (age, sex, type and concentration of serum and/or urine monoclonal component, international prognostic index, presence of bone lesion, and chromosomal abnormalities). However, flow cytometric evaluation of the myeloma cells revealed that CD56, which is one of the adhesion molecules N-CAM, expressed more than 45 % in all responders, while those expressed less than 5 % in all nonresponders (84 ± 19 (±SD) % v/s 4 ± 2 %, P=0.017). Furthermore, CD56 expression of the myeloma cells was reduced from 84% to 70 ± 32 % after Thal therapy in all evaluated responders (P =0.048). These results suggest that CD56 expression of the myeloma cells could be the potent prognostic marker of the Thal efficacy. Moreover, it was reported that Thal reduced the expression of cell adhesion molecules, such as LFA-1 and ICAM-1, and abrogated the binding of MM cells to bone marrow stromal cells, that triggered the secretion of interleukin-6 and vascular endothelial growth factor. Taken together, it was suggested that Thal reduced the expression of CD56 and altered the MM cell adhesion to bone marrow stromal cells, and that could be one of the pathogenesis of anti-MM activity of Thal.


2014 ◽  
Vol 168 (1) ◽  
pp. 139-142 ◽  
Author(s):  
Sandrine T. Lafarge ◽  
Hongzhao Li ◽  
Samantha D. Pauls ◽  
Sen Hou ◽  
James B. Johnston ◽  
...  

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4836-4836
Author(s):  
Satoki Nakamura ◽  
Miki Kobayashi ◽  
Kiyoshi Shibata ◽  
Naohi Sahara ◽  
Kazuyuki Shigeno ◽  
...  

Abstract Cyclooxygenase-2 (COX-2) is reported to regulate apoptosis and to be an important cellular target for therapy. In this study, we demonstrated that etodolac, a COX-2 inhibitor, inhibited proliferation and induced apoptosis in myeloma cell lines (RPMI 8226 and MC/CAR cells), expressing the COX-2 enzyme. In both cell lines, etodolac more strongly induced apoptosis compared with thalidomide or meloxicam. Etodolac induced down-regulation of bcl-2 protein and mRNA, activation of caspase-9, -7 and -3, down-regulation of caspase inhibitors, cIAP-1 and survivin, and loss of mitochondrial membrane potential in a dose-dependent manner. In addition, our data demonstrated that when myeloma cells were coincubated with 50 mM etodolac on bone marrow stromal cells (BMSC), myeloma cell adhesion to BMSC was significantly inhibited compared with thalidomide or meloxicam coincubation, and the adhesion molecules VLA-4, LFA-1 (CD11a), CXCX4, and CD44 were suppressed on myeloma cells treated with etodolac. Moreover, we found that 100 mM R-etodolac, S-etodolac, and the combination of R- and S-etodolac, which are the stereoisomers of etodolac, slightly inhibited the proliferation of myeloma cells, while 50 to 100 mM etodolac significantly inhibited the proliferation of myeloma cells. In conclusion, our findings indicate that etodolac induced apoptosis via a bcl-2 dependent pathway, suppressed the expression of adhesion molecules, and inhibited myeloma cell adhesion to BMSC compared with thalidomide or meloxicam. Thus, the activities of etodolac potentially extend to the treatment of patients with myeloma resistant to standard chemotherapy, including thalidomide.


2010 ◽  
Vol 299 (2) ◽  
pp. C422-C430 ◽  
Author(s):  
Haiyan Li ◽  
Richard Daculsi ◽  
Maritie Grellier ◽  
Reine Bareille ◽  
Chantal Bourget ◽  
...  

In our previous studies, roles of gap junction and vascular endothelial growth factor in the cross-talking of human bone marrow stromal cells (HBMSCs) and human umbilical vein endothelial cells (HUVECs) have been extensively studied. The present study focused on the investigation of the roles of neural (N)-cadherin in early differentiation of HBMSCs in direct-contact cocultures with HUVECs for 24 and 48 h. Quantitative real-time polymerase chain reaction, immunofluorescence, Western blot, as well as functional studies were applied to perform the studies at both protein and gene levels. Results showed that cocultured cells expressed much higher N-cadherin than monocultured cells after 24 and 48 h of culture. We observed that N-cadherin concentrated in the membrane of cocultured HBMSCs (co-HBMSCs) while distributed within the cytoplasm of monocultured HBMSCs, which indicated that the cell-cell adhesion was improved between cocultured cells. In addition, more β-catenin was found to translocate into the cocultured cells nuclei and more T cell factor-1 (TCF-1) were detected in cocultured cells than in the monocultured cells. Moreover, mRNA levels of early osteoblastic markers including alkaline phosphatase (ALP) and type I collagen (Col-I) of co-HBMSCs were significantly upregulated, whereas neutralization of N-cadherin led to a downregulation of ALP and Col-I in both of the HBMSCs and co-HBMSCs compared with untreated cells. Taking our findings together it can be concluded that cocultures of HBMSCs with HUVECs increased N-cadherin expression and improved cell-cell adhesion. Whether this applies only to osteoprogenitor cells or to all the cell types in the culture will need to be determined by further studies. Subsequently, signaling transduction might be induced with the participation of β-catenin and TCF-1. With the N-cadherin-mediated cell-cell adhesion and signaling transductions, the early osteoblastic differentiation of co-HBMSCs was significantly upregulated.


2012 ◽  
Vol 1403 ◽  
Author(s):  
Seyedsina Moeinzadeh ◽  
Danial Barati ◽  
Xuezhong He ◽  
Esmaiel Jabbari

ABSTRACTIn this work, a novel star 4-arm poly(ethylene glycol-co-lactide) acrylate macromonomer (SPELA) is synthesized, and the effect of macromonomer concentration and architecture on modulus, swelling ratio and sol fraction is investigated. The results show that the storage modulus of the hydrogel had an increasing trend with polymer concentration. Changing the polymer architecture from linear to 4-arm increased the storage modulus by 2.2-fold. The water content depended on the hydrophilic segment density as well as the extent of crosslinking and showed a decreasing trend with macromonomer concentration. The sol fractions of the SPELA hydrogels changed from 13% to 5% when concentration increased from 10% to 25%. The star SPELA hydrogel with high modulus, fast gelation time, and low sol fraction is potential useful as a degradable carrier in cell-based therapies. Results show that the SPELA hydrogel supports viability and osteogenic differentiation of the encapsulated bone marrow stromal cells.


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