Corneal stroma-derived mesenchymal stem cells(CS-MSCs) are mainly distributed in the anterior part of the corneal stroma near the corneal limbal stem cells(LSCs). CS-MSCs are stem cells with self-renewal and multidire...Corneal stroma-derived mesenchymal stem cells(CS-MSCs) are mainly distributed in the anterior part of the corneal stroma near the corneal limbal stem cells(LSCs). CS-MSCs are stem cells with self-renewal and multidirectional differentiation potential. A large amount of data confirmed that CS-MSCs can be induced to differentiate into functional keratocytes in vitro, which is the motive force for maintaining corneal transparency and producing a normal corneal stroma. CS-MSCs are also an important component of the limbal microenvironment. Furthermore, they are of great significance in the reconstruction of ocular surface tissue and tissue engineering for active biocornea construction. In this paper, the localization and biological characteristics of CS-MSCs, the use of CS-MSCs to reconstruct a tissue-engineered active biocornea, and the repair of the limbal and matrix microenvironment by CS-MSCs are reviewed, and their application prospects are discussed.展开更多
The efficacy of nanoparticle(NP)-based drug delivery technology is hampered by aberrant tumor stromal microenvironments(TSMs)that hinder NP transportation.Therefore,the promotion of NP permeation into deep tumor sites...The efficacy of nanoparticle(NP)-based drug delivery technology is hampered by aberrant tumor stromal microenvironments(TSMs)that hinder NP transportation.Therefore,the promotion of NP permeation into deep tumor sites via the regulation of tumor microenvironments is of critical importance.Herein,we propose a potential solution using a dihydralazine(HDZ)-loaded nanoparticle drug delivery system containing a pH-responsive,cyclic RGD peptide-modified prodrug based on doxorubicin(cRGD-Dex-DOX).With a combined experimental and theoretical approach,we find that the designed NP system can recognize the acid tumor environments and precisely release the encapsulated HDZ into tumor tissues.HDZ can notably downregulate the expression levels of hypoxia-inducible factor 1α(HIF1α),α-smooth muscle actin,and fibronectin through the dilation of tumor blood vessels.These changes in the TSMs enhance the enrichment and penetration of NPs and also unexpectedly promote the infiltration of activated T cells into tumors,suggesting that such a system may offer an effective“multifunctional therapy”through both improving the chemotherapeutic effect and enhancing the immune response to tumors.In vivo experiments on 4T1 breast cancer bearing mice indeed validate that this therapy has the most outstanding antitumor effects over all the other tested control regimens,with the lowest side effects as well.展开更多
基金Supported by the National Key R&D Program of China (No.2016YFC1100100)the Key R&D Program of Shaanxi Province (No.2018ZDXM-SF-056)+2 种基金the Health and Family Planning Research Fund Project of Shaanxi Province (No.2016C004)the Key Research and Development Program of Shaanxi Province (No.2019SF-196)the Research Talent Project of Xi’an Municipal Health Commission (No.J201902037)。
文摘Corneal stroma-derived mesenchymal stem cells(CS-MSCs) are mainly distributed in the anterior part of the corneal stroma near the corneal limbal stem cells(LSCs). CS-MSCs are stem cells with self-renewal and multidirectional differentiation potential. A large amount of data confirmed that CS-MSCs can be induced to differentiate into functional keratocytes in vitro, which is the motive force for maintaining corneal transparency and producing a normal corneal stroma. CS-MSCs are also an important component of the limbal microenvironment. Furthermore, they are of great significance in the reconstruction of ocular surface tissue and tissue engineering for active biocornea construction. In this paper, the localization and biological characteristics of CS-MSCs, the use of CS-MSCs to reconstruct a tissue-engineered active biocornea, and the repair of the limbal and matrix microenvironment by CS-MSCs are reviewed, and their application prospects are discussed.
基金National Key Research and Development Program of China,Grant/Award Numbers:2021YFA1201200,2021YFF1200404National Natural Science Foundation of China,Grant/Award Numbers:U1967217,22176137+5 种基金National Independent Innovation Demonstration Zone Shanghai Zhangjiang Major Projects,Grant/Award Number:ZJZX2020014National Center of Technology Innovation for Biopharmaceuticals,Grant/Award Number:NCTIB2022HS02010Shanghai Artificial Intelligence Lab,Grant/Award Number:P22KN00272Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study,Grant/Award Number:SN-ZJU-SIAS-003Natural Science Foundation of the Jiangsu Higher Education Institutions of China,Grant/Award Number:20KJA150010Natural Science Foundation of Zhejiang Province,Grant/Award Number:2022LQ22H220001。
文摘The efficacy of nanoparticle(NP)-based drug delivery technology is hampered by aberrant tumor stromal microenvironments(TSMs)that hinder NP transportation.Therefore,the promotion of NP permeation into deep tumor sites via the regulation of tumor microenvironments is of critical importance.Herein,we propose a potential solution using a dihydralazine(HDZ)-loaded nanoparticle drug delivery system containing a pH-responsive,cyclic RGD peptide-modified prodrug based on doxorubicin(cRGD-Dex-DOX).With a combined experimental and theoretical approach,we find that the designed NP system can recognize the acid tumor environments and precisely release the encapsulated HDZ into tumor tissues.HDZ can notably downregulate the expression levels of hypoxia-inducible factor 1α(HIF1α),α-smooth muscle actin,and fibronectin through the dilation of tumor blood vessels.These changes in the TSMs enhance the enrichment and penetration of NPs and also unexpectedly promote the infiltration of activated T cells into tumors,suggesting that such a system may offer an effective“multifunctional therapy”through both improving the chemotherapeutic effect and enhancing the immune response to tumors.In vivo experiments on 4T1 breast cancer bearing mice indeed validate that this therapy has the most outstanding antitumor effects over all the other tested control regimens,with the lowest side effects as well.
