Compressed Collagen Enhances Stem Cell Therapy for Corneal Scarring

Stem cells translational medicine - Tập 7 Số 6 - Trang 487-494 - 2018
Golnar Shojaati1,2, Irona Khandaker2, Kyle Sylakowski2, Martha L. Funderburgh2, Yiqin Du2, James L. Funderburgh2
1aDepartment of Ophthalmology Kantonsspital Winterthur, Zurich, Switzerland
2bDepartment of Ophthalmology University of Pittsburgh, Pittsburgh, Pennsylvania, USA

Tóm tắt

Abstract Stem cells from human corneal stroma (CSSC) suppress corneal stromal scarring in a mouse wound-healing model and promote regeneration of native transparent tissue (PMID:25504883). This study investigated efficacy of compressed collagen gel (CCG) as a vehicle to deliver CSSC for corneal therapy. CSSC isolated from limbal stroma of human donor corneas were embedded in soluble rat-tendon collagen, gelled at 37°C, and partially dehydrated to a thickness of 100 µm by passive absorption. The CCG disks were dimensionally stable, easy to handle, and could be adhered securely to de-epithelialized mouse cornea with fibrin-based adhesive. CSSC in CCG maintained >80% viability for >1 week in culture media and could be cryopreserved in 20% fetal bovine serum-10%DMSO in liquid nitrogen. CCG containing as few as 500 CSSC effectively prevented visible scarring and suppressed expression of fibrotic Col3a1 mRNA. CSSC in CCG were more effective at blocking scarring on a per-cell basis than CSSC delivered directly in a fibrin gel as previously described. Collagen-embedded cells retained the ability to suppress corneal scarring after conventional cryopreservation. This study demonstrates use of a common biomaterial that can facilitate storage and handling of stem cells in a manner that may provide off-the-shelf delivery of stem cells as a therapy for corneal scarring.

Từ khóa


Tài liệu tham khảo

Whitcher, 1997, Corneal ulceration in the developing world–a silent epidemic, Br J Ophthalmol, 81, 622, 10.1136/bjo.81.8.622

Basu, 2014, Human limbal biopsy-derived stromal stem cells prevent corneal scarring, Sci Transl Med, 6, 266ra172, 10.1126/scitranslmed.3009644

Funderburgh, 2016, Stem cells in the limbal stroma, Ocul Surf, 14, 113, 10.1016/j.jtos.2015.12.006

Hertsenberg, 2017, Corneal stromal stem cells reduce corneal scarring by mediating neutrophil infiltration after wounding, PLoS One, 12, e0171712, 10.1371/journal.pone.0171712

Hu, 2010, Compressed collagen gel as the scaffold for skin engineering, Biomed Microdevices, 12, 627, 10.1007/s10544-010-9415-4

Vaissiere, 2000, Comparative analysis of different collagen-based biomaterials as scaffolds for long-term culture of human fibroblasts, Med Biol Eng Comput, 38, 205, 10.1007/BF02344778

Lee, 2001, Biomedical applications of collagen, Int J Pharm, 221, 1, 10.1016/S0378-5173(01)00691-3

Jones, 2002, A guide to biological skin substitutes, Br J Plast Surg, 55, 185, 10.1054/bjps.2002.3800

Auger, 2004, Tissue-engineered skin substitutes: From in vitro constructs to in vivo applications, Biotechnol Appl Biochem, 39, 263, 10.1042/BA20030229

Jimenez, 2004, Tissue and cellular approaches to wound repair, Am J Surg, 187, 56S, 10.1016/S0002-9610(03)00305-2

Buznyk, 2015, Bioengineered corneas grafted as alternatives to human donor corneas in three high-risk patients, Clin Transl Sci, 8, 558, 10.1111/cts.12293

Charulatha, 2003, Influence of different crosslinking treatments on the physical properties of collagen membranes, Biomaterials, 24, 759, 10.1016/S0142-9612(02)00412-X

Brown, 2005, Ultrarapid engineering of biomimetic materials and tissues: Fabrication of nano- and microstructures by plastic compression, Adv Funct Mater, 15, 1762, 10.1002/adfm.200500042

Buxton, 2008, Dense collagen matrix accelerates osteogenic differentiation and rescues the apoptotic response to MMP inhibition, Bone, 43, 377, 10.1016/j.bone.2008.03.028

Bitar, 2007, Effect of multiple unconfined compression on cellular dense collagen scaffolds for bone tissue engineering, J Mater Sci Mater Med, 18, 237, 10.1007/s10856-006-0685-1

Kureshi, 2015, Human corneal stromal stem cells support limbal epithelial cells cultured on RAFT tissue equivalents, Sci Rep, 5, 16186, 10.1038/srep16186

Levis, 2016, Recreating the human limbal epithelial stem cell niche with bioengineered limbal crypts, Curr Eye Res, 41, 1153, 10.3109/02713683.2015.1095932

Massie, 2015, Limbal fibroblasts maintain normal phenotype in 3D RAFT tissue equivalents suggesting potential for safe clinical use in treatment of ocular surface failure, Tissue Eng Part C Methods, 21, 576, 10.1089/ten.tec.2014.0458

Massie, 2014, Response of human limbal epithelial cells to wounding on 3D RAFT tissue equivalents: Effect of airlifting and human limbal fibroblasts, Exp Eye Res, 127, 196, 10.1016/j.exer.2014.07.024

Funderburgh, 2008, Keratocyte phenotype is enhanced in the absence of attachment to the substratum, Mol Vis, 14, 308

Boote, 2012, Quantitative assessment of ultrastructure and light scatter in mouse corneal debridement wounds, Invest Ophthalmol Vis Sci, 53, 2786, 10.1167/iovs.11-9305

Zhang, 2013, The measurement of corneal thickness from center to limbus in vivo in C57BL/6 and BALB/c mice using two-photon imaging, Exp Eye Res, 115, 255, 10.1016/j.exer.2013.07.025

Henriksson, 2009, Dimensions and morphology of the cornea in three strains of mice, Invest Ophthalmol Vis Sci, 50, 3648, 10.1167/iovs.08-2941

Funderburgh, 1998, Decorin and biglycan of normal and pathologic human corneas, Invest Ophthalmol Vis Sci, 39, 1957

Guo, 2010, Hyaluronan synthesis mediates the fibrotic response of keratocytes to transforming growth factor beta, J Biol Chem, 285, 32012, 10.1074/jbc.M110.127183

Ylostalo, 2012, Human mesenchymal stem/stromal cells cultured as spheroids are self-activated to produce prostaglandin E2 that directs stimulated macrophages into an anti-inflammatory phenotype, Stem Cells, 30, 2283, 10.1002/stem.1191

Bian, 2016, Differential effects of dexamethasone and doxycycline on inflammation and MMP production in murine alkali-burned corneas associated with dry eye, Ocul Surf, 14, 242, 10.1016/j.jtos.2015.11.006

Ramshaw, 2016, Biomedical applications of collagens, J Biomed Mater Res B Appl Biomater, 104, 665, 10.1002/jbm.b.33541

Brodsky, 2017, Bioengineered collagens, Subcell Biochem, 82, 601, 10.1007/978-3-319-49674-0_18

Thông tin
Thông tin xuất bản

Stem cells translational medicine

Tập 7 Số 6

487-494

Thông tin tác giả