Chondrogenesis of mesenchymal stem cells and dedifferentiated chondrocytes by transfection with SOX Trio genes

Yang, Han Na; Park, Ji Sun; Woo, Dae Gyun; Jeon, Sang Goo; Do, Hyun-Jin; Lim, Hye-Young; Kim, Seung Who; Kim, Jaehwan; Park, Keun-Hong

doi:10.1016/j.biomaterials.2011.06.059

Cited by 43 publications

(41 citation statements)

References 39 publications

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“…Specifically, hMSCs and fibroblast cells could progress through chondrogenic, osteogenic, or adipogenic differentiation in response to the transfection with SOX9, C/EBP-and Runx2 genes complexed with PLGA NPs, respectively. 33 34 50 These studies demonstrated that the PLGA NPs complexed with specific genes improved the efficiency of gene transfection into hMSCs and also enhanced the differentiation of hMSCs into desired cell types. In the present study, we developed a PLGA NPs system, through a simple fabrication of polyplex by coupling the cationic NPs and anionic pDNAs.…”

Section: Discussionmentioning

confidence: 93%

“…29 The Bak-like (BL) protein, which are a pro-apoptotic protein homolog of Bak generated by alternative splicing of the Bak gene, was first identified by Kim et al 30 BL contains BH1 and BH2 (but not BH3) domains and can induce apoptosis as well, though it is less potent than Bak, Cationic polymer-coated NPs one of the most commonly used and extensively studied non-viral gene delivery vehicles. [31][32][33][34] The transfection of specific genes into cancer cells is a highly effective method to induce cell death; however, its inherent instability and low transfection efficiency result in extremely low bioavailability of the protein(s) of interest, which leads to low anticancer activity in vivo. In the present study, we developed biodegradable PLGA NPs coated with PEI polymers, which were then complexed with two apoptosis-inducing genes Bak and BL.…”

Section: Introductionmentioning

confidence: 99%

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Complexation of Apoptotic Genes with Polyethyleneimine (PEI)-Coated Poly-(DL)-Lactic-Co-Glycolic Acid Nanoparticles for Cancer Cell Apoptosis

Lim¹,

Kim²,

Park³

2015

j biomed nanotechnol

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Methods for delivering genes into the nuclei of cancer cells are desired in various clinical and therapeutic usages of non-viral vectors. The present study describes the production of surface-modified poly-(DL)-lactic-co-glycolic acid (PLGA) nanoparticles (NPs), which facilitated the delivery of specific genes into the cancer cell nuclei. Plasmid DNA (pDNA) encoding Bak and Bak-like (BL) apoptotic genes were generated and successfully delivered into cancer cell nuclei, resulting in apoptosis of the cancer cells. The abilities of Bak and BL genes to promote cancer cell (HeLa and 293T cells) apoptosis were compared. In fluorescence-activated cell sorting (FACS) analysis, approximately 61% and 51% of BL pDNAs fused with EGFP complexed PLGA NPs were transfected into 293T cells and HeLa cells, respectively; however, a low transfection efficiency was obtained for lipofectamine-complexed BL pDNAs. In both DePsipher and cytochrome c staining analysis, larger amount of apoptotic 293T and HeLa cells were observed after cell transfection with Bak and BL pDNAs complexed with PLGA NPs as compared with lipofectamine complexed with Bak and BL pDNAs or control groups. The apoptosis of 293T and HeLa cells transfected with Bak and BL against several types of non-viral vectors was detected. Western blotting, and immunohistochemical analyses showed that the complexes of biodegradable PLGA NPs coated with polyethyleneimine (PEI; M w 25,000) Bak and BL can be formed, and used for efficient delivery of the apoptotic genes into the cell nuclei.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Complexation of Apoptotic Genes with Polyethyleneimine (PEI)-Coated Poly-(DL)-Lactic-Co-Glycolic Acid Nanoparticles for Cancer Cell Apoptosis

Lim¹,

Kim²,

Park³

2015

j biomed nanotechnol

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“…5 In this regard, approaches based on the transfer of sequences coding for chondrogenic and/or chondroreparative factors may offer strong tools to enhance the healing response of the articular cartilage through transplantation of genetically modified isolated or concentrated progenitor cells. 16 While a broad number of therapeutic candidates have been evaluated to target isolated MSCs (cartilage oligomeric matrix protein, COMP; transforming growth factor beta, TGF-b; bone morphogenetic proteins, BMPs; insulinlike growth factor I, IGF-I; basic fibroblast growth factor, FGF-2; Indian hedgehog, IHH; human telomerase, hTERT; small interfering RNA (siRNA) against p53; SOX transcription factors; anti-Runx2/Cbfa1 siRNA; zinc-finger protein 145, ZNF145), [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] relatively few information is available on the feasibility of translating the method to marrow concentrates as a less invasive treatment strategy. Most notably, Pascher et al 34 and Ivkovic et al 35 employed adenoviral gene transfer to transduce marrow aspirates from rabbit and sheep, achieving relatively short-term levels of transgene expression in such samples in vitro (21 days).…”

Section: Introductionmentioning

confidence: 99%

Chondrogenic Differentiation Processes in Human Bone Marrow Aspirates upon rAAV-Mediated Gene Transfer and Overexpression of the Insulin-Like Growth Factor I

Frisch

Rey‐Rico

Venkatesan

et al. 2015

Tissue Engineering Part A

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Direct therapeutic gene transfer in marrow concentrates is an attractive strategy to conveniently enhance the chondrogenic differentiation processes as a means to improve the healing response of damaged articular cartilage upon reimplantation in sites of injury. In the present study, we evaluated the ability of the clinically adapted recombinant adeno-associated virus (rAAV) vectors to mediate overexpression of the insulin-like growth factor I (IGF-I) in human bone marrow aspirates that may modulate the proliferative, anabolic activities, and chondrogenic differentiation potential in such samples in vitro. The results demonstrate that successful, significant rAAV-mediated IGF-I gene transfer and expression were achieved in transduced aspirates (up to 105.9 -35.1 pg rhIGF-I/mg total proteins) over time (21 days) at very high levels (*80% of cells expressing the candidate IGF-I transgene), leading to increased levels of proliferation, matrix synthesis, and chondrogenic differentiation over time compared with the control (lacZ) condition. Treatment with the candidate IGF-I vector also stimulated the hypertrophic and osteogenic differentiation processes in the aspirates, suggesting that the regulation of IGF-I expression through rAAV will be a prerequisite for future translation of the approach in vivo. However, these findings show the possible benefits of this vector class to directly modify marrow concentrates as a convenient tool for strategies that aim at improving the repair of articular cartilage lesions.

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“…For bone formation, studies regarding gene combinations of BMP-2 and VEGF, BMP-2, 212 223,224 and TGF-b3 and collagen I silencing short hairpin RNA. 225 Osteochondral defects have also received particular interest by the combination of BMP-2 and TGF-b1.…”

Section: From Single To Multiple Bioactive Factor Delivery For Skeletmentioning

confidence: 99%

Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

Santo

Gomes²,

Mano³

et al. 2013

Tissue Engineering Part B: Reviews

105

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The development of controlled release systems for the regeneration of bone, cartilage, and osteochondral interface is one of the hot topics in the field of tissue engineering and regenerative medicine. However, the majority of the developed systems consider only the release of a single growth factor, which is a limiting step for the success of the therapy. More recent studies have been focused on the design and tailoring of appropriate combinations of bioactive factors to match the desired goals regarding tissue regeneration. In fact, considering the complexity of extracellular matrix and the diversity of growth factors and cytokines involved in each biological response, it is expected that an appropriate combination of bioactive factors could lead to more successful outcomes in tissue regeneration. In this review, the evolution on the development of dual and multiple bioactive factor release systems for bone, cartilage, and osteochondral interface is overviewed, specifically the relevance of parameters such as dosage and spatiotemporal distribution of bioactive factors. A comprehensive collection of studies focused on the delivery of bioactive factors is also presented while highlighting the increasing impact of platelet-rich plasma as an autologous source of multiple growth factors.

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Chondrogenesis of mesenchymal stem cells and dedifferentiated chondrocytes by transfection with SOX Trio genes

Cited by 43 publications

References 39 publications

Complexation of Apoptotic Genes with Polyethyleneimine (PEI)-Coated Poly-(DL)-Lactic-Co-Glycolic Acid Nanoparticles for Cancer Cell Apoptosis

Complexation of Apoptotic Genes with Polyethyleneimine (PEI)-Coated Poly-(DL)-Lactic-Co-Glycolic Acid Nanoparticles for Cancer Cell Apoptosis

Chondrogenic Differentiation Processes in Human Bone Marrow Aspirates upon rAAV-Mediated Gene Transfer and Overexpression of the Insulin-Like Growth Factor I

Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

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