nach oben

Die Ophthalmologie

Erschienen in:

04.04.2017 | Leitthema

Evaluierung neuer Biomaterialien und alternativer Stammzellpopulationen zur Rekonstruktion der Limbusstammzellnische

verfasst von: PD Dr. P. Eberwein, T. Reinhard

Erschienen in: Die Ophthalmologie | Ausgabe 4/2017

Einloggen, um Zugang zu erhalten

Zusammenfassung

Die Rekonstruktion der Limbusstammzellnische bei Limbusstammzellinsuffizienz ist nach wie vor eine der größten therapeutischen Herausforderungen bei Erkrankungen der Augenoberfläche. Die Ex-vivo-Expansion von Limbusstammzellen bedarf trotz bereits in einigen wenigen Zentren erreichter positiver Erfahrungen noch weiterer Optimierung bezüglich einer optimalen Rekonstruktion der Limbusstammzellnische. Auch alternative Stammzellquellen mit höherem Proliferations- und Differenzierungspotenzial wurden und müssen zukünftig vermehrt evaluiert werden. In die alternativen autologen Stammzellquellen wird insbesondere bei der beidseitigen kompletten Limbusstammzellinsuffizienz große Hoffnung gesetzt, denn nur bei ihrer Verwendung lassen sich immunologische Komplikationen umgehen. Im Bereich des Tissue-Engineering haben sich in den letzten Jahren zahlreiche neue Biomaterialien zur Rekonstruktion der Limbusstammzellnische hervorgetan, die allesamt zum Ziel haben, die Nische bestmöglich hinsichtlich zellulärer, anatomischer und biomechanischer Aspekte zu rekonstruieren. Ziel dieser Übersicht soll es sein, einen Überblick über neue Biomaterialien und Stammzellpopulationen im Kontext der Rekonstruktion der Limbusstammzellnische zu geben.

Ahmadiankia N, Ebrahimi M, Hosseini A, Baharvand H (2009) Effects of different extracellular matrices and co-cultures on human limbal stem cell expansion in vitro. Cell Biol Int 33:978–987. doi: 10.1016/j.cellbi.2009.06.019 CrossRefPubMed

Altman GH, Diaz F, Jakuba C et al (2003) Silk-based biomaterials. Biomaterials 24:401–416 CrossRefPubMed

Ananta M, Brown RA, Mudera V (2012) A rapid fabricated living dermal equivalent for skin tissue engineering: an in vivo evaluation in an acute wound model. Tissue Eng Part A 18:353–361. doi: 10.1089/ten.TEA.2011.0208 CrossRefPubMed

Bar-Nur O, Brumbaugh J, Verheul C et al (2014) Small molecules facilitate rapid and synchronous iPSC generation. Nat Methods 11:1170–1176. doi: 10.1038/nmeth.3142 CrossRefPubMedPubMedCentral

Borooah S, Phillips MJ, Bilican B et al (2013) Using human induced pluripotent stem cells to treat retinal disease. Prog Retin Eye Res 37:163–181. doi: 10.1016/j.preteyeres.2013.09.002 CrossRefPubMedPubMedCentral

Bray LJ, George KA, Ainscough SL et al (2011) Human corneal epithelial equivalents constructed on Bombyx mori silk fibroin membranes. Biomaterials 32:5086–5091. doi: 10.1016/j.biomaterials.2011.03.068 CrossRefPubMed

Bray LJ, George KA, Hutmacher DW et al (2012) A dual-layer silk fibroin scaffold for reconstructing the human corneal limbus. Biomaterials 33:3529–3538. doi: 10.1016/j.biomaterials.2012.01.045 CrossRefPubMed

Brown RA, Wiseman M, Chuo C et al (2005) Ultrarapid engineering of biomimetic materials and tissues: fabrication of nano-and microstructures by plastic compression. Adv Funct Mater 15:1762–1770 CrossRef

Buxton PG, Bitar M, Gellynck K et al (2008) Dense collagen matrix accelerates osteogenic differentiation and rescues the apoptotic response to MMP inhibition. Bone 43:377–385. doi: 10.1016/j.bone.2008.03.028 CrossRefPubMed

10.

Chen S‑Y, Hayashida Y, Chen M‑Y et al (2011) A new isolation method of human limbal progenitor cells by maintaining close association with their niche cells. Tissue Eng Part C Methods 17:537–548. doi: 10.1089/ten.TEC.2010.0609 CrossRefPubMedPubMedCentral

11.

Chirila T, Barnard Z, Zainuddin et al (2008) Bombyx mori silk fibroin membranes as potential substrata for epithelial constructs used in the management of ocular surface disorders. Tissue Eng Part A 14:1203–1211. doi: 10.1089/ten.tea.2007.0224 CrossRefPubMed

12.

Chirila TV, Barnard Z, Zainuddin Z, Harkin D (2007) Silk as substratum for cell attachment and proliferation. Mater Sci Forum 561-565:1549–1552 CrossRef

13.

Demura M, Asakura T (1991) Porous membrane of Bombyx mori silk fibroin: structure characterization, physical properties and application to glucose oxidase immobilization. J Memb Sci 59:39–52 CrossRef

14.

Deshpande P, McKean R, Blackwood KA et al (2010) Using poly(lactide-co-glycolide) electrospun scaffolds to deliver cultured epithelial cells to the cornea. Regen Med 5:395–401. doi: 10.2217/rme.10.16 CrossRefPubMed

15.

Deshpande P, Ramachandran C, Sangwan VS, Macneil S (2013) Cultivation of limbal epithelial cells on electrospun poly (lactide-co-glycolide) scaffolds for delivery to the cornea. Methods Mol Biol 1014:179–185. doi: 10.1007/978-1-62703-432-6_12 CrossRefPubMed

16.

Deshpande P, Ramachandran C, Sefat F et al (2013) Simplifying corneal surface regeneration using a biodegradable synthetic membrane and limbal tissue explants. Biomaterials 34:5088–5106. doi: 10.1016/j.biomaterials.2013.03.064 CrossRefPubMed

17.

Dietrich-Ntoukas T, Hofmann-Rummelt C, Kruse FE, Schlötzer-Schrehardt U (2012) Comparative analysis of the basement membrane composition of the human limbus epithelium and amniotic membrane epithelium. Cornea 31:564–569. doi: 10.1097/ICO.0b013e3182254b78 CrossRefPubMed

18.

Dziasko MA, Daniels JT (2016) Anatomical features and cell-cell interactions in the human limbal epithelial stem cell niche. Ocul Surf 14:322–330. doi: 10.1016/j.jtos.2016.04.002 CrossRefPubMed

19.

East E, de Oliveira DB, Golding JP, Phillips JB (2010) Alignment of astrocytes increases neuronal growth in three-dimensional collagen gels and is maintained following plastic compression to form a spinal cord repair conduit. Tissue Eng Part A 16:3173–3184. doi: 10.1089/ten.tea.2010.0017 CrossRefPubMedPubMedCentral

20.

Eberwein P, Böhringer D, Schwartzkopff J et al (2012) Allogenic limbo-keratoplasty with conjunctivoplasty, mitomycin C, and amniotic membrane for bilateral limbal stem cell deficiency. Ophthalmology 119:930–937. doi: 10.1016/j.ophtha.2011.10.039 CrossRefPubMed

21.

Eberwein P, Laird D, Schulz S et al (2015) Modulation of focal adhesion constituents and their down-stream events by EGF: on the cross-talk of integrins and growth factor receptors. Biochim Biophys Acta 1853:2183–2198. doi: 10.1016/j.bbamcr.2015.06.004 CrossRefPubMed

22.

Eberwein P, Nohava J, Schlunck G, Swain M (2014) Nanoindentation derived mechanical properties of the corneoscleral rim of the human eye. Key Eng Mater 606:117–120 CrossRef

23.

Eberwein P, Reinhard T (2015) Concise reviews: the role of biomechanics in the limbal stem cell niche: new insights for our understanding of this structure. Stem Cells 33:916–924. doi: 10.1002/stem.1886 CrossRefPubMed

24.

Eberwein P, Steinberg T, Schulz S et al (2011) Expression of keratinocyte biomarkers is governed by environmental biomechanics. Eur J Cell Biol 90:1029–1040. doi: 10.1016/j.ejcb.2011.08.005 CrossRefPubMed

25.

Engler AJ, Sen S, Sweeney HL, Discher DE (2006) Matrix elasticity directs stem cell lineage specification. Cell 126:677–689. doi: 10.1016/j.cell.2006.06.044 CrossRefPubMed

26.

Grueterich M, Espana EM, Tseng SCG (2003) Ex vivo expansion of limbal epithelial stem cells: amniotic membrane serving as a stem cell niche. Surv Ophthalmol 48:631–646 CrossRefPubMed

27.

Gu S, Xing C, Han J et al (2009) Differentiation of rabbit bone marrow mesenchymal stem cells into corneal epithelial cells in vivo and ex vivo. Mol Vis 15:99–107 PubMedPubMedCentral

28.

Harkin DG, George KA, Madden PW et al (2011) Silk fibroin in ocular tissue reconstruction. Biomaterials 32:2445–2458. doi: 10.1016/j.biomaterials.2010.12.041 CrossRefPubMed

29.

Hayashida Y, Nishida K, Yamato M et al (2005) Ocular surface reconstruction using autologous rabbit oral mucosal epithelial sheets fabricated ex vivo on a temperature-responsive culture surface. Invest Ophthalmol Vis Sci 46:1632–1639. doi: 10.1167/iovs.04-0813 CrossRefPubMed

30.

Higa K, Takeshima N, Moro F, Kawakita T, Kawashima M, Demura M, Shimazaki J, Asakura T, Tsubota K, Shimmura S (2011) Porous silk fibroin film as a transparent carrier for cultivated corneal epithelial sheets. J Biomater Sci Polym Ed 22(17):2261–2276. doi:10.1163/092050610X538218

31.

Hodgkinson T, Chen Y, Bayat A, Yuan X‑F (2014) Rheology and electrospinning of regenerated bombyx mori silk fibroin aqueous solutions. Biomacromolecules 15:1288–1298. doi: 10.1021/bm4018319 CrossRefPubMed

32.

Holle AW, Engler AJ (2011) More than a feeling: discovering, understanding, and influencing mechanosensing pathways. Curr Opin Biotechnol 22:648–654. doi: 10.1016/j.copbio.2011.04.007 CrossRefPubMedPubMedCentral

33.

Huang M, Li N, Wu Z et al (2011) Using acellular porcine limbal stroma for rabbit limbal stem cell microenvironment reconstruction. Biomaterials 32:7812–7821. doi: 10.1016/j.biomaterials.2011.07.012 CrossRefPubMed

34.

Inatomi T, Nakamura T, Koizumi N et al (2006) Midterm results on ocular surface reconstruction using cultivated autologous oral mucosal epithelial transplantation. Am J Ophthalmol 141:267–275. doi: 10.1016/j.ajo.2005.09.003 CrossRefPubMed

35.

Jiang T‑S, Cai L, Ji W‑Y et al (2010) Reconstruction of the corneal epithelium with induced marrow mesenchymal stem cells in rats. Mol Vis 16:1304–1316 PubMedPubMedCentral

36.

Jin H‑J, Fridrikh SV, Rutledge GC, Kaplan DL (2002) Electrospinning Bombyx mori silk with poly(ethylene oxide). Biomacromolecules 3:1233–1239 CrossRefPubMed

37.

Jones RR, Hamley IW, Connon CJ (2012) Ex vivo expansion of limbal stem cells is affected by substrate properties. Stem Cell Res 8:403–409. doi: 10.1016/j.scr.2012.01.001 CrossRefPubMed

38.

Kolli S, Lako M, Figueiredo F et al (2008) Loss of corneal epithelial stem cell properties in outgrowths from human limbal explants cultured on intact amniotic membrane. Regen Med 3:329–342. doi: 10.2217/17460751.3.3.329 CrossRefPubMed

39.

Lawrence BD, Pan Z, Liu A et al (2012) Human corneal limbal epithelial cell response to varying silk film geometric topography in vitro. Acta Biomater 8:3732–3743. doi: 10.1016/j.actbio.2012.06.009 CrossRefPubMedPubMedCentral

40.

de Lázaro I, Yilmazer A, Kostarelos K (2014) Induced pluripotent stem (iPS) cells: A new source for cell-based therapeutics? J Control Release. doi: 10.1016/j.jconrel.2014.04.011 PubMed

41.

Levis HJ, Brown RA, Daniels JT (2010) Plastic compressed collagen as a biomimetic substrate for human limbal epithelial cell culture. Biomaterials 31:7726–7737. doi: 10.1016/j.biomaterials.2010.07.012 CrossRefPubMed

42.

Levis HJ, Massie I, Dziasko MA et al (2013) Rapid tissue engineering of biomimetic human corneal limbal crypts with 3D niche architecture. Biomaterials 34:8860–8868. doi: 10.1016/j.biomaterials.2013.08.002 CrossRefPubMed

43.

Li G‑G, Zhu Y‑T, Xie H‑T et al (2012) Mesenchymal stem cells derived from human limbal niche cells. Invest Ophthalmol Vis Sci 53:5686–5697. doi: 10.1167/iovs.12-10300 CrossRefPubMedPubMedCentral

44.

Lynch AP, Ahearne M (2013) Strategies for developing decellularized corneal scaffolds. Exp Eye Res 108:42–47. doi: 10.1016/j.exer.2012.12.012 CrossRefPubMed

45.

Ma DH-K, Kuo M‑T, Tsai Y‑J et al (2009) Transplantation of cultivated oral mucosal epithelial cells for severe corneal burn. Eye 23:1442–1450. doi: 10.1038/eye.2009.60 CrossRefPubMed

46.

Massie I, Dziasko M, Kureshi A et al (2015) Advanced imaging and tissue engineering of the human limbal epithelial stem cell niche. Methods Mol Biol 1235:179–202. doi: 10.1007/978-1-4939-1785-3_15 CrossRefPubMedPubMedCentral

47.

Ma Y, Xu Y, Xiao Z et al (2006) Reconstruction of chemically burned rat corneal surface by bone marrow-derived human mesenchymal stem cells. Stem Cells 24:315–321. doi: 10.1634/stemcells.2005-0046 CrossRefPubMed

48.

Mei H, Gonzalez S, Deng SX (2012) Extracellular matrix is an important component of limbal stem cell niche. J Funct Biomater 3:879–894. doi: 10.3390/jfb3040879 CrossRefPubMedPubMedCentral

49.

Meller D, Thomasen H (2017) Limbusstammzelltransplantation. Aktueller Stand und Perspektiven. Ophthalmologe, doi: 10.1007/s00347-017-0462-6

50.

Mikhailova A, Ilmarinen T, Uusitalo H, Skottman H (2014) Small-molecule induction promotes corneal epithelial cell differentiation from human induced pluripotent stem cells. Stem Cell Reports 2:219–231. doi: 10.1016/j.stemcr.2013.12.014 CrossRefPubMedPubMedCentral

51.

Miri A, Al-Deiri B, Dua HS (2010) Long-term outcomes of autolimbal and allolimbal transplants. Ophthalmology 117:1207–1213. doi: 10.1016/j.ophtha.2009.10.028 CrossRefPubMed

52.

Mi S, Chen B, Wright B, Connon CJ (2010) Plastic compression of a collagen gel forms a much improved scaffold for ocular surface tissue engineering over conventional collagen gels. J Biomed Mater Res A 95:447–453. doi: 10.1002/jbm.a.32861 CrossRefPubMed

53.

Moers K, Steinberg T, Schlunck G et al (2013) Substrate elasticity as biomechanical modulator of tissue homeostatic parameters in corneal keratinocytes. Exp Cell Res 319:1889–1901. doi: 10.1016/j.yexcr.2013.05.002 CrossRefPubMed

54.

Nakamura T, Takeda K, Inatomi T et al (2011) Long-term results of autologous cultivated oral mucosal epithelial transplantation in the scar phase of severe ocular surface disorders. Br J Ophthalmol 95:942–946. doi: 10.1136/bjo.2010.188714 CrossRefPubMed

55.

Nieto-Miguel T, Galindo S, Reinoso R et al (2013) In vitro simulation of corneal epithelium microenvironment induces a corneal epithelial-like cell phenotype from human adipose tissue mesenchymal stem cells. Curr Eye Res 38:933–944. doi: 10.3109/02713683.2013.802809 CrossRefPubMed

56.

Ott HC, Matthiesen TS, Goh S‑K et al (2008) Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat Med 14:213–221. doi: 10.1038/nm1684 CrossRefPubMed

57.

Reinhard T, Kontopoulos T, Wernet P et al (2004) Long-term results of homologous penetrating limbokeratoplasty in total limbal stem cell insufficiency after chemical/thermal burns. Ophthalmologe 101:682–687. doi: 10.1007/s00347-003-0839-6 CrossRefPubMed

58.

Reinhard T, Spelsberg H, Henke L et al (2004) Long-term results of allogeneic penetrating limbo-keratoplasty in total limbal stem cell deficiency. Ophthalmology 111:775–782. doi: 10.1016/j.ophtha.2003.07.013 CrossRefPubMed

59.

Salehi S, Grünert AK, Bahners T et al (2014) New nanofibrous scaffold for corneal tissue engineering. Klin Monatsbl Augenheilkd 231:626–630. doi: 10.1055/s-0034-1368533 CrossRefPubMed

60.

Satake Y, Higa K, Tsubota K, Shimazaki J (2011) Long-term outcome of cultivated oral mucosal epithelial sheet transplantation in treatment of total limbal stem cell deficiency. Ophthalmology 118:1524–1530. doi: 10.1016/j.ophtha.2011.01.039 CrossRefPubMed

61.

Schulz S, Beck D, Laird D et al (2014) Natural corneal cell-based microenvironment as prerequisite for balanced 3D corneal epithelial morphogenesis: a promising animal experiment-abandoning tool in ophthalmology. Tissue Eng Part C Methods 20:297–307. doi: 10.1089/ten.TEC.2013.0195 CrossRefPubMed

62.

Sharma S, Gupta D, Mohanty S et al (2014) Surface-modified electrospun poly(epsilon-caprolactone) scaffold with improved optical transparency and bioactivity for damaged ocular surface reconstruction. Invest Ophthalmol Vis Sci 55:899–907. doi: 10.1167/iovs.13-12727 CrossRefPubMed

63.

Sheth R, Neale MH, Shortt AJ et al (2015) Culture and characterization of oral mucosal epithelial cells on a fibrin gel for ocular surface reconstruction. Curr Eye Res 40:1077–1087. doi: 10.3109/02713683.2014.978477 CrossRefPubMed

64.

Shortt AJ, Secker GA, Munro PM et al (2007) Characterization of the limbal epithelial stem cell niche: novel imaging techniques permit in vivo observation and targeted biopsy of limbal epithelial stem cells. Stem Cells 25:1402–1409. doi: 10.1634/stemcells.2006-0580 CrossRefPubMed

65.

Stadtfeld M, Nagaya M, Utikal J et al (2008) Induced pluripotent stem cells generated without viral integration. Science 322:945–949. doi: 10.1126/science.1162494 CrossRefPubMedPubMedCentral

66.

Sundmacher R, Reinhard T (1998) Homologous lamellar central limbokeratoplasty in severe limbal stem cell deficiency. Klin Monatsbl Augenheilkd 213:254–255. doi: 10.1055/s-2008-1034984 CrossRefPubMed

67.

Sutherland AJ, Beck EC, Dennis SC et al (2015) Decellularized cartilage may be a chondroinductive material for osteochondral tissue engineering. PLOS ONE 10:e0121966. doi: 10.1371/journal.pone.0121966 CrossRefPubMedPubMedCentral

68.

Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676. doi: 10.1016/j.cell.2006.07.024 CrossRefPubMed

69.

Tamada Y (2005) New process to form a silk fibroin porous 3‑D structure. Biomacromolecules 6:3100–3106. doi: 10.1021/bm050431f CrossRefPubMed

70.

Tseng SCG, Meller D, Anderson DF et al (2002) Ex vivo preservation and expansion of human limbal epithelial stem cells on amniotic membrane for treating corneal diseases with total limbal stem cell deficiency. Adv Exp Med Biol 506:1323–1334 CrossRefPubMed

71.

Uygun BE, Soto-Gutierrez A, Yagi H et al (2010) Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat Med 16:814–820. doi: 10.1038/nm.2170 CrossRefPubMedPubMedCentral

72.

Wan P‑X, Wang B‑W, Wang Z‑C (2015) Importance of the stem cell microenvironment for ophthalmological cell-based therapy. World J Stem Cells 7:448–460. doi: 10.4252/wjsc.v7.i2.448 CrossRefPubMedPubMedCentral

73.

Wiley LA, Burnight ER, Songstad AE et al (2015) Patient-specific induced pluripotent stem cells (iPSCs) for the study and treatment of retinal degenerative diseases. Prog Retin Eye Res 44:15–35. doi: 10.1016/j.preteyeres.2014.10.002 CrossRefPubMed

74.

Xie H‑T, Chen S‑Y, Li G‑G, Tseng SCG (2012) Isolation and expansion of human limbal stromal niche cells. Invest Ophthalmol Vis Sci 53:279–286. doi: 10.1167/iovs.11-8441 CrossRefPubMedPubMedCentral

75.

Yoeruek E, Bayyoud T, Maurus C et al (2012) Decellularization of porcine corneas and repopulation with human corneal cells for tissue-engineered xenografts. Acta Ophthalmol (Copenh) 90:e125–e131. doi: 10.1111/j.1755-3768.2011.02261.x CrossRef

Titel: Evaluierung neuer Biomaterialien und alternativer Stammzellpopulationen zur Rekonstruktion der Limbusstammzellnische
verfasst von: PD Dr. P. Eberwein
T. Reinhard
Publikationsdatum: 04.04.2017
Verlag: Springer Medizin
Erschienen in: Die Ophthalmologie / Ausgabe 4/2017
Print ISSN: 2731-720X
Elektronische ISSN: 2731-7218
DOI: https://doi.org/10.1007/s00347-017-0463-5

Neu im Fachgebiet Augenheilkunde

09.05.2023 | Chekpoint-Inhibitoren | CME

Springer Medizin

Evaluierung neuer Biomaterialien und alternativer Stammzellpopulationen zur Rekonstruktion der Limbusstammzellnische

Zusammenfassung

Neu im Fachgebiet Augenheilkunde

Okuläre Nebenwirkungen moderner onkologischer Therapie

Diagnostik des okulären Schleimhautpemphigoids

Immunpathogenese des Schleimhautpemphigoids

Erste Ergebnisse des Deutschen okulären Pemphigoid-Registers

Springer Medizin

Zusammenfassung

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2017

Zukunftstechnologie Tissue-﻿Engineering

Limbusstammzelltransplantation

Kontrastsehen – Definitionen, Umrechnungen und Äquivalenztabelle

Mitteilungen der DOG

Katarakt durch Blitzschlag. Erstbeschreibung

Stammzellbasierte Ansätze bei Erkrankungen der Augenoberfläche

Neu im Fachgebiet Augenheilkunde

Okuläre Nebenwirkungen moderner onkologischer Therapie

Diagnostik des okulären Schleimhautpemphigoids

Immunpathogenese des Schleimhautpemphigoids

Erste Ergebnisse des Deutschen okulären Pemphigoid-Registers

Zukunftstechnologie Tissue-Engineering