The roles of nanocarriers on pigment epithelium-derived factor in the differentiation of human cardiac stem cells.
Over the past decade, adult stem cells have attracted great attention because of their ability to potentially regenerate desired tissues or entire organs. With the emergence of nanomaterial-based gene therapy, adult stem cells have been considered as a proper tool for the biomedical field. In this study, we utilized organically modified silica (ORMOSIL) nanoparticles to deliver small interfering RNA (siRNA) against pigment epithelium-derived factor (PEDF) and induce the differentiation of human cardiac stem cells (CSCs). We found that the down-regulation of PEDF can inhibit the proliferation of human CSCs and induce cell differentiation. To further study the mechanism, we have tested the Notch signalling pathway genes, Hes1 and Hes5, and found that their expressions were inhibited by the PEDF down-regulation. Furthermore, with the restoration of PEDF, both the proliferation of human CSCs and expressions of Hes1 and Hes5 were recovered. Our results suggest for the first time the use of ORMOSIL as nanocarriers for the delivery of PEDF siRNA in human CSCs, and demonstrated the cooperation between PEDF and the Notch signalling pathway in maintaining the self-renewal and pluripotency of stem cells. PEDF as the essential controller in differentiation may be a promising target for the regulation of cardiac homeostasis and damage repair, which opens new treatment strategies using nanomaterials for heart disease therapy.
Department of Cardiovascular Surgery, Institute of Cardiovascular Disease of Chinese PLA, Xijing Hospital, The Fourth Military Medical University, No.169 West Changle Road, Xi'an, 710032, Shanxi, China.
Hongliang
H
Liang
Department of Cardiovascular Surgery, Institute of Cardiovascular Disease of Chinese PLA, Xijing Hospital, The Fourth Military Medical University, No.169 West Changle Road, Xi'an, 710032, Shanxi, China.
Weixun
W
Duan
Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, China.
Huiyuan
H
Hou
Department of Cardiovascular Surgery, Institute of Cardiovascular Disease of Chinese PLA, Xijing Hospital, The Fourth Military Medical University, No.169 West Changle Road, Xi'an, 710032, Shanxi, China.
Wei
W
Yi
Department of Cardiovascular Surgery, Institute of Cardiovascular Disease of Chinese PLA, Xijing Hospital, The Fourth Military Medical University, No.169 West Changle Road, Xi'an, 710032, Shanxi, China.
Jinzhou
J
Zhang
Department of Cardiovascular Surgery, Institute of Cardiovascular Disease of Chinese PLA, Xijing Hospital, The Fourth Military Medical University, No.169 West Changle Road, Xi'an, 710032, Shanxi, China.
Zhenxiao
Z
Jin
Department of Cardiovascular Surgery, Institute of Cardiovascular Disease of Chinese PLA, Xijing Hospital, The Fourth Military Medical University, No.169 West Changle Road, Xi'an, 710032, Shanxi, China.
Mengen
M
Zhai
Department of Cardiovascular Surgery, Institute of Cardiovascular Disease of Chinese PLA, Xijing Hospital, The Fourth Military Medical University, No.169 West Changle Road, Xi'an, 710032, Shanxi, China.
Shiqiang
S
Yu
Department of Cardiovascular Surgery, Institute of Cardiovascular Disease of Chinese PLA, Xijing Hospital, The Fourth Military Medical University, No.169 West Changle Road, Xi'an, 710032, Shanxi, China. jinchengliu11@163.com.
Jincheng
J
Liu
Department of Cardiovascular Surgery, Institute of Cardiovascular Disease of Chinese PLA, Xijing Hospital, The Fourth Military Medical University, No.169 West Changle Road, Xi'an, 710032, Shanxi, China. dinghuayi1@163.com.
Dinghua
D
Yi
D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D015536:Down-Regulation; D004337:Drug Carriers / Q000737:chemistry*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D009206:Myocardium / Q000166:cytology*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D012822:Silicon Dioxide / Q000737:chemistry; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
D004337:Drug Carriers; D005136:Eye Proteins; D009414:Nerve Growth Factors; D034741:RNA, Small Interfering; D051880:Receptors, Notch; D015843:Serpins; D012822:Silicon Dioxide; D000099174:Pigment Epithelium-Derived Factor
Differentiation; Human cardiac stem cells; Notch; ORMOSIL; PEDF; Self-renewal