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

Yi Zhou; Xiaobo Xia; Enzhi Yang; Yiwen Wang; Kacey G. Marra; C. Ross Ethier; Joel S. Schuman; Yiqin Du

doi:10.1096/fj.201902326R

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

Yi Zhou, Xiaobo Xia, Enzhi Yang, Yiwen Wang, Kacey G. Marra, C. Ross Ethier, Joel S. Schuman, Yiqin Du

Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Pages (from-to)	7160-7177
Number of pages	18
Journal	FASEB Journal
Volume	34
Issue number	5
DOIs	https://doi.org/10.1096/fj.201902326R
State	Published - May 1 2020

Keywords

adipose stem cells; differentiation
homing
integration
trabecular meshwork

ASJC Scopus subject areas

Biotechnology
Biochemistry
Molecular Biology
Genetics

Access to Document

10.1096/fj.201902326R

Cite this

@article{7d4dbb426756488e98f9993dd16d76d0,

title = "Adipose-derived stem cells integrate into trabecular meshwork with glaucoma treatment potential",

abstract = "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.",

keywords = "adipose stem cells; differentiation, homing, integration, trabecular meshwork",

author = "Yi Zhou and Xiaobo Xia and Enzhi Yang and Yiwen Wang and Marra, {Kacey G.} and Ethier, {C. Ross} and Schuman, {Joel S.} and Yiqin Du",

note = "Funding Information: This work was supported by NIH grants EY025643 (YD), EY025286 (CRE), P30‐EY008098; Eye and Ear Foundation (Pittsburgh, PA); Research to Prevent Blindness; and an anonymous philanthropic donation (YD). We thank Ms Min Sun at Center for Biologic Imaging at University of Pittsburgh for TEM work. Funding Information: This work was supported by NIH grants EY025643 (YD), EY025286 (CRE),?P30-EY008098; Eye and Ear Foundation (Pittsburgh, PA); Research to Prevent Blindness; and an anonymous philanthropic donation (YD). We thank Ms Min Sun at Center for Biologic Imaging at University of Pittsburgh for TEM work. Publisher Copyright: {\textcopyright} 2020 Federation of American Societies for Experimental Biology",

year = "2020",

month = may,

day = "1",

doi = "10.1096/fj.201902326R",

language = "English (US)",

volume = "34",

pages = "7160--7177",

journal = "FASEB Journal",

issn = "0892-6638",

publisher = "FASEB",

number = "5",

}

TY - JOUR

T1 - Adipose-derived stem cells integrate into trabecular meshwork with glaucoma treatment potential

AU - Zhou, Yi

AU - Xia, Xiaobo

AU - Yang, Enzhi

AU - Wang, Yiwen

AU - Marra, Kacey G.

AU - Ethier, C. Ross

AU - Schuman, Joel S.

AU - Du, Yiqin

N1 - Funding Information: This work was supported by NIH grants EY025643 (YD), EY025286 (CRE), P30‐EY008098; Eye and Ear Foundation (Pittsburgh, PA); Research to Prevent Blindness; and an anonymous philanthropic donation (YD). We thank Ms Min Sun at Center for Biologic Imaging at University of Pittsburgh for TEM work. Funding Information: This work was supported by NIH grants EY025643 (YD), EY025286 (CRE),?P30-EY008098; Eye and Ear Foundation (Pittsburgh, PA); Research to Prevent Blindness; and an anonymous philanthropic donation (YD). We thank Ms Min Sun at Center for Biologic Imaging at University of Pittsburgh for TEM work. Publisher Copyright: © 2020 Federation of American Societies for Experimental Biology

PY - 2020/5/1

Y1 - 2020/5/1

N2 - 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.

AB - 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.

KW - adipose stem cells; differentiation

KW - homing

KW - integration

KW - trabecular meshwork

UR - http://www.scopus.com/inward/record.url?scp=85082930724&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85082930724&partnerID=8YFLogxK

U2 - 10.1096/fj.201902326R

DO - 10.1096/fj.201902326R

M3 - Article

C2 - 32259357

AN - SCOPUS:85082930724

SN - 0892-6638

VL - 34

SP - 7160

EP - 7177

JO - FASEB Journal

JF - FASEB Journal

IS - 5

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this