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1.
Nanomedicine ; 24: 102141, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31830613

RESUMO

Lysyl oxidase (LOX) is a cell-secreted amine oxidase that crosslinks collagen and elastin in extracellular microenvironment. LOX-traceable nanoparticles (LOXab-NPs) consisting of LOX antibodies (LOXab) and paclitaxel, can accumulate at high concentrations at radiation-treated target sites, as a tumor-targeting drug carrier for chemotherapy. Tumor-targeting and anticancer effects of PLGA based LOXab-NPs in vitro and in vivo were evaluated at radiation-targeted site. In the in vivo A549 lung carcinoma xenograft model, we showed highly specific tumor targeting (above 7.0 times higher) of LOXab-NPs on irradiated tumors. Notably, systemically administered NPs delayed tumor growth, reducing tumor volumes by more than 2 times compared with non-irradiated groups (222% vs. >500%) over 2 weeks. Radiotropic LOXab-NPs can serve as chemotherapeutic vehicles for combined targeted chemo-radiotherapy in clinical oncology.


Assuntos
Apoptose/efeitos da radiação , Nanopartículas/química , Nanopartículas/uso terapêutico , Proteína-Lisina 6-Oxidase/metabolismo , Radiação Ionizante , Células A549 , Animais , Western Blotting , Células Cultivadas , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Proteína-Lisina 6-Oxidase/química , Ensaios Antitumorais Modelo de Xenoenxerto
2.
J Tissue Eng Regen Med ; 12(4): 890-896, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28478656

RESUMO

Clinical irradiation therapy for cancer could increase the risk of localized wound complications. This study was conducted to evaluate the potential use of a chitosan microparticle-pluronic F127 (CSMP-PF) hydrogel complex containing bioactive molecules, substance P and transforming growth factor-ß1, to regeneratively repair skin damaged by local ionizing radiation (IR). The BALB/c/bkl mice were locally irradiated to their limbs with a single 40 Gy dose of Co-60 γ rays to induce a skin injury. The morphological characteristics of the chitosan microparticles were analysed by scanning electron microscopy. The amounts of bioactive molecules taken up and released by the CSMP-PF hydrogel complex were measured. Haematoxylin and eosin staining of IR-damaged skin showed acanthosis and hyperkeratosis in the epidermis; and damage to hair follicles/skin appendages and adipose tissue, as well as panniculus carnosus, in the dermis. Injection of the CSMP-PF hydrogel complex into IR-damaged skin resulted in skin repair, suggesting that the complex has potential for use in the regenerative repair of IR-damaged skin.


Assuntos
Quitosana , Raios gama/efeitos adversos , Hidrogéis , Lesões Experimentais por Radiação , Substância P , Fator de Crescimento Transformador beta , Cicatrização/efeitos dos fármacos , Animais , Quitosana/química , Quitosana/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Lesões Experimentais por Radiação/tratamento farmacológico , Lesões Experimentais por Radiação/patologia , Pele/lesões , Pele/metabolismo , Pele/patologia , Substância P/química , Substância P/farmacologia , Fator de Crescimento Transformador beta/química , Fator de Crescimento Transformador beta/farmacologia
3.
Tissue Eng Regen Med ; 14(4): 421-432, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30603498

RESUMO

Mesenchymal stem cells (MSCs), which are multipotent and have self-renewal ability, support the regeneration of damaged normal tissue. A number of external stimuli promote migration of MSCs into peripheral blood and support their participation in wound healing. In an attempt to harness the potential beneficial effects of such external stimuli, we exposed human MSCs (hMSCs) to one such stimulus-low-dose ionizing radiation (LDIR)-and examined their biological properties. To this end, we evaluated differences in proliferation, cell cycle, DNA damage, expression of surface markers (CD29, CD34, CD90, and CD105), and differentiation potential of hMSCs before and after irradiation with γ-rays generated using a 137CS irradiator. At doses less than 50 mGy, LDIR had no significant effect on the viability or apoptosis of hMSCs. Interestingly, 10 mGy of LDIR increased hMSC viability by 8% (p < 0.001) compared with non-irradiated hMSCs. At doses less than 50 mGy, LDIR did not induce DNA damage, including DNA strand breaks, or cause cellular senescence or cell-cycle arrest. Surface marker expression and in vitro differentiation potential of hMSCs were maintained after two exposures to LDIR at 10 mGy per dose. In conclusion, a two-dose exposure to LDIR at 10 mGy per dose not only facilitates proliferation of hMSCs, it also maintains the stem cell characteristics of hMSCs without affecting their viability. These results provide evidence for the potential of LDIR as an external stimulus for in vitro expansion of hMSCs and application in tissue engineering and regenerative medicine.

4.
Int J Mol Sci ; 17(1)2016 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-26751441

RESUMO

The goal to successful wound healing is essentially to immobilize and recruit appropriate numbers of host stem or progenitor cells to the wound area. In this study, we developed a chitosan nanofiber-immobilized neuropeptide substance-P (SP), which mediates stem cell mobilization and migration, onto the surfaces of nanofibers using a peptide-coupling agent, and evaluated its biological effects on stem cells. The amount of immobilized SP on chitosan nanofibers was modulated over the range of 5.89 ± 3.27 to 75.29 ± 24.31 ng when reacted with 10 to 500 ng SP. In vitro migration assays showed that SP-incorporated nanofibers induced more rapid migration of human mesenchymal stem cells on nanofibers compared to pristine samples. Finally, the conjugated SP evoked a minimal foreign body reaction and recruited a larger number of CD29- and CD44-positive stem cells into nanofibers in a mouse subcutaneous pocket model.


Assuntos
Movimento Celular/efeitos dos fármacos , Quitosana/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Nanofibras/química , Neurotransmissores/farmacologia , Substância P/farmacologia , Alicerces Teciduais/química , Animais , Feminino , Humanos , Células-Tronco Mesenquimais/citologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanofibras/ultraestrutura , Neurotransmissores/administração & dosagem , Neurotransmissores/química , Substância P/administração & dosagem , Substância P/química , Engenharia Tecidual/métodos , Cicatrização/efeitos dos fármacos
5.
Stem Cells Transl Med ; 3(11): 1381-91, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25205841

RESUMO

Reconstruction of elastic cartilage requires a source of chondrocytes that display a reliable differentiation tendency. Predetermined tissue progenitor cells are ideal candidates for meeting this need; however, it is difficult to obtain donor elastic cartilage tissue because most elastic cartilage serves important functions or forms external structures, making these tissues indispensable. We found vestigial cartilage tissue in xiphoid processes and characterized it as hyaline cartilage in the proximal region and elastic cartilage in the distal region. Xiphoid process-derived chondrocytes (XCs) showed superb in vitro expansion ability based on colony-forming unit fibroblast assays, cell yield, and cumulative cell growth. On induction of differentiation into mesenchymal lineages, XCs showed a strong tendency toward chondrogenic differentiation. An examination of the tissue-specific regeneration capacity of XCs in a subcutaneous-transplantation model and autologous chondrocyte implantation model confirmed reliable regeneration of elastic cartilage regardless of the implantation environment. On the basis of these observations, we conclude that xiphoid process cartilage, the only elastic cartilage tissue source that can be obtained without destroying external shape or function, is a source of elastic chondrocytes that show superb in vitro expansion and reliable differentiation capacity. These findings indicate that XCs could be a valuable cell source for reconstruction of elastic cartilage.


Assuntos
Diferenciação Celular , Condrócitos , Cartilagem Hialina , Regeneração , Processo Xifoide , Animais , Autoenxertos , Células Cultivadas , Condrócitos/citologia , Condrócitos/metabolismo , Condrócitos/transplante , Cartilagem Hialina/citologia , Cartilagem Hialina/fisiologia , Masculino , Ratos , Ratos Sprague-Dawley , Processo Xifoide/citologia , Processo Xifoide/metabolismo
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