Adipose-derived stem cells integrate into trabecular meshwork with glaucoma treatment potential

被引:25
作者
Zhou, Yi [1 ,2 ]
Xia, Xiaobo [2 ]
Yang, Enzhi [1 ]
Wang, Yiwen [1 ,2 ]
Marra, Kacey G. [3 ,4 ]
Ethier, C. Ross [5 ,6 ]
Schuman, Joel S. [7 ]
Du, Yiqin [1 ,4 ,8 ]
机构
[1] Univ Pittsburgh, Dept Ophthalmol, 910 EEINS,203 Lothrop St, Pittsburgh, PA 15213 USA
[2] Cent South Univ, Xiangya Hosp, Dept Ophthalmol, Changsha, Peoples R China
[3] Univ Pittsburgh, Dept Plast Surg & Bioengn, Pittsburgh, PA 15213 USA
[4] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA 15213 USA
[5] Georgia Inst Technol, Dept Biomed Engn, Atlanta, GA 30332 USA
[6] Emory Univ, Atlanta, GA 30322 USA
[7] NYU, Dept Ophthalmol, Sch Med, 550 1St Ave, New York, NY 10016 USA
[8] Univ Pittsburgh, Dept Dev Biol, Pittsburgh, PA 15213 USA
关键词
adipose stem cells; differentiation; homing; integration; trabecular meshwork; OPEN-ANGLE GLAUCOMA; OCULAR HYPERTENSION TREATMENT; LINKED ACTIN NETWORKS; IN-VITRO; INTRAOCULAR-PRESSURE; TISSUE; OUTFLOW; TRANSPLANTATION; INDUCTION; MODEL;
D O I
10.1096/fj.201902326R
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The trabecular meshwork (TM) is an ocular tissue that maintains intraocular pressure (IOP) within a physiologic range. Glaucoma patients have reduced TM cellularity and, frequently, elevated IOP. To establish a stem cell-based approach to restoring TM function and normalizing IOP, human adipose-derived stem cells (ADSCs) were induced to differentiate to TM cells in vitro. These ADSC-TM cells displayed a TM cell-like genotypic profile, became phagocytic, and responded to dexamethasone stimulation, characteristic of TM cells. After transplantation into naive mouse eyes, ADSCs and ADSC-TM cells integrated into the TM tissue, expressed TM cell markers, and maintained normal IOP, outflow facility, and extracellular matrix. Cell migration and affinity results indicated that the chemokine pair CXCR4/SDF1 may play an important role in ADSC-TM cell homing. Our study demonstrates the possibility of applying autologous or allogeneic ADSCs and ADSC-TM cells as a potential treatment to restore TM structure and function in glaucoma.
引用
收藏
页码:7160 / 7177
页数:18
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