Zusammenfassung
Hintergrund: Der Heilungsprozess kornealer Defekte setzt funktionsfähige Limbusstammzellen voraus. Deren Verlust führt zur sekundären Wundheilungsstörung. Die Stammzellforschung eröffnet neue Therapiemöglichkeiten. Material und Methoden: Selektive Medline Recherche in der amerikanischen National Library of Medicine. Ergebnisse: Die autologe Limbusstammzelltransplantation ist derzeit die Therapie der Wahl. Eine andere klinisch erprobte Möglichkeit ist die Transplantation einer Amnionmembran, die zuvor mit Limbusstammzellen besiedelt wurde. Tierexperimentell sind auch knochenmarkisolierte mesenchymale oder epidermale Stammzellen zur Besiedlung verwendet worden. Fettisolierte mesenchymale Stammzellen können ebenfalls die Regenerationsfähigkeit der Kornea unterstützen. Überdies ist die Membrantransplantation, die aus Epithelzellen der Mundschleimhaut in vitro gezüchtet wurde, klinisch erprobt. Diskussion und Schlussfolgerungen: Beidseitige Limbusstammzellinsuffizienz ist der limitierende Faktor einer autologen Limbusstammzelltransplantation. Allogen transplantierte Limbusstammzellen müssen vor Destruktion durch Immunsuppression geschützt werden. Epithelzellen, epidermale Stammzellen, knochenmark- oder fettisolierte mesenchymale Stammzellen fördern die Regeneration der Kornea und scheinen für die Therapie der Korneadefekte geeignet zu sein. Die mesenchymalen Stammzellen bieten zum anderen den Vorteil einer entzündungshemmenden Wirkung, inhibieren in vitro die Proliferation allogener T-Zellen und führen nach allogener und xenogener Transplantation zu keiner Abstoßungsreaktion.
Abstract
Background: The healing process of corneal defects requires functioning limbus stem cells. Their loss will lead to secondary wound healing problems. Stem cell research offers new treatment options. Material and Methods: A Medline search of the U. S. National Library of Medicine was carried out. Results: The autologous limbus stem cell transplantation is currently the treatment of choice. Amniotic membrane transplantation, previously settled with limbus stem cells, is a clinically proven method. In animal experiments bone marrow-derived mesenchymal stem cells or epidermal stem cells can be used to improve healing of corneal defects. Adipose-derived stem cells may support the regenerative ability of the cornea as well. Moreover, membrane transplantation of epithelial cells from the buccal mucosa cultivated in vitro was clinically tested. Discussion and Conclusions: Limbus stem cell failure of both eye is the limiting factor for autologous limbus stem cell transplantation. Epithelial cells, epidermal stem cells, bone marrow- or adipose-derived mesenchymal stem cells promote the regeneration of the cornea and have become established for the treatment of corneal defects. Additionally, mesenchymal stem cells offer the advantage of immunosuppressive and anti-inflammatory effects.
Schlüsselwörter
Kornea - Trauma - Stammzelle
Key words
cornea - trauma - stem cells
Literatur
-
1
Lavker R M, Tseng S C, Sun T T.
Corneal epithelial stem cells at the limbus: looking at some old problems from a new angle.
Exp Eye Res.
2004;
78
433-446
-
2
Meller D, Kruse F.
Ex-vivo-Expansion kornealer Stammzellen Experimentelle Grundlagen und erste klinische Ergebnisse.
Der Ophthalmologe.
2001;
98 (9)
811-817
-
3
Evans M J.
The isolation and properties of a clonal tissue culture strain of pluripotent mouse teratoma cells.
J Embryol Exp Morphol.
1972;
28
163-167
-
4
Thomson J A, Itskovitz-Eldor J, Shapiro S S. et al .
Embryonic Stem Cell Lines Derived from Human Blastocysts.
Science.
1998;
282
1145-1147
-
5
Shamblott M J, Axelman J, Wang S. et al .
Derivation of pluripotent stem cells from cultured human primordial germ cells.
Proc Natl Acad Sci USA.
1998;
95 (23)
13726-13731
-
6
Gearhart J D.
New potential for human embryonic stem cells.
Science.
1998;
282
1145-1147
-
7
Stewart C L, Gadi I, Bhatt H.
Stem cells from primordial germ cells can reenter the germ line.
Dev Biol.
1994;
161
626-628
-
8
Surani M A.
Reprogramming a somatic nucleus by trans-modification activity in germ cells.
Semin Cell Dev Biol.
1999;
10
273-277
-
9
French A J, Adams C A, French A J. et al .
Development of human cloned blastocysts following somatic cell nuclear transfer with adult fibroblasts.
Stem Cells.
2008;
26 (2)
485-493
-
10
Friedenstein A J, Gorskaja J F, Kulagina N N.
Fibroblast precusors in normal and irradiated mouse hematopoetic organs.
Exp Hematol.
1976;
4
267-274
-
11
Janes S M, Lowell S, Hutter C.
Epidermal stem cells.
J Pathol.
2002;
197
479-491
-
12
Lees S J, Zwetsloot K A, Booth F W.
Circulating Skeletal Stem Cells.
J Cell Biol.
2001;
153
1133-1140
-
13
Péchoux C, Gudjonsson T, Ronnov-Jessen L. et al .
Human mammary luminal epithelial cells contain progenitors to myoepithelial cells.
Dev Biol.
1999;
206
88-89
-
14
Reynolds B A, Weiss S.
Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system.
Science.
1992;
255
1707-1710
-
15
Maunoury R, Robine S, Pringault E. et al .
Developmental regulation of villin gene expression in the epithelial cell lineages of mouse digestive and urogenital tracts.
Development.
1992;
115
717-728
-
16
Gimble J M.
Adipose tissue-derived therapeutics.
Expert Opin Biol Ther.
2003;
3
705-713
-
17
Romanov Y A, Svintsitskaya V A, Smirnov V N.
Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord.
Stem cells.
2003;
21
105-110
-
18
Shi S, Gronthos S.
Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp.
J Bone Miner Res.
2003;
18
696-704
-
19
Young R W.
Cell proliferation during postnatal development of the retina in the mouse.
Brain Res.
1985;
353 (2)
229-239
-
20
Spangrude G J, Heimfeld S, Weissman I L.
Purification and characterization of mouse hematopoietic stem cells.
Science.
1988;
241
58-62
-
21
Buckner C D, Epstein R B, Rudolph R H. et al .
Allogeneic marrow engraftment following whole body irradiation in a patient with leukemia.
Blood.
1970;
35
741-750
-
22
Friedenstein A J, Deriglasova U F, Kulagina N N. et al .
Precursors for fibroblasts in different populations of hematopoietic cells of hhematopoetic cells as detected by in vitro colony assay method.
Exp Hematol.
1974;
2
83-92
-
23
Sanchez-Ramos J, Song S, Cardozo-Pelaez F. et al .
Adult bone marrow stromal cells differentiate into neural cells in vitro.
Exp Neurol.
2000;
164 (2)
247-256
-
24
Zuk P A, Zhu M, Mizuno H. et al .
Multilineage cells from human adipose tissue: Implications for cell-based therapies.
Tissue Eng.
2001;
7
211-228
-
25
Muraglia A, Cancedda R, Quarto R.
Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model.
J cell Sci.
2000;
113
1161-1166
-
26
Pountos I, Giannoudis P V.
Biology of mesenchymal stem cells.
Int J Care Injured.
2005;
365
S8-S12
-
27
Tsuchida H, Hashimoto J, Crawford E. et al .
Engineered human mesenchymal stem cells repair femoral defect in rats.
J Orthop Res.
2003;
21
44-53
-
28
Saito T, Kuang J Q, Lin C C. et al .
Transcoronary implantation of bone marrow stromal cells ameliorates cardiac function after myocardial infarction.
J Thorac Cardiovasc Surg.
2003;
126
114-123
-
29
Guo T, Wang W, Zhang J. et al .
Experimental study on repairing damage of corneal surface by mesenchymal stem cells transplantation.
Zhonghua Yan Ke Za Zhi.
2006;
42 (3)
246-250
-
30
Ma Y, Xu Y, Xiao Z. et al .
Reconstruction of chemically burned rat corneal surface by bone marrow-derived human mesenchymal stem cells.
Stem Cells.
2006;
24
315-321
-
31
Ye J, Lee S Y, Kook K H. et al .
Bone marrow-derived progenitor cells promote corneal wound healing following alkali injury.
Graefes Arch Clin Exp Ophthalmol.
2008;
246 (2)
217-222
-
32
Choong P F, Mok P L, Cheong S K. et al .
Mesenchymal stromal cell-like characteristics of corneal keratocytes.
Cytotherapy.
2007;
9 (3)
252-258
-
33
Naresh P, Anees F, Soundarya L M. et al .
Mesenchymal cells from limbal stroma of human eye.
Mol Vis.
2008;
14
431-442
-
34
Arnalich-Montiela F, Pastorb S, Blazquez-Martineza A. et al .
Adipose-derived stem cells are a source for cell therapy of the corneal stroma.
Stem Cells.
2008;
26
570-579
-
35
Tsai R J, Li L M, Chen J K.
Reconstruction of damaged corneas by transplantation of autologous limbal epithelial cells.
N Engl J Med.
2000;
343 (2)
86-93
-
36
Koizumi N, Inatomi T, Suzuki T. et al .
Cultivated corneal epithelial stem cell transplantation in ocular surface disorders.
Ophthalmology.
2001;
108 (9)
1569-1574
-
37
Kim J T, Chun Y S, Song K Y. et al .
The effect of in vivo grown corneal epithelium transplantation on persistent epithelial defects with limbal stem cell deficiency.
J Korean Med Sci.
2008;
23
502-508
-
38
Stoiber J, Ruckhofer J, Muss W. et al .
Amnion-Limbus-Transplantation zur Oberflächenrekonstruktion nach schwererVerätzung und Verbrennung.
Der Ophthalmologe.
2002;
99 (11)
839-848
-
39
Yang X, Moldovan N I, Zhao Q. et al .
Reconstruction of damaged cornea by autologous transplantation of epidermal adult stem cells.
Mol Vis.
2008;
14
1064-1074
-
40
Nishida K, Yamato M, Hayashida Y. et al .
Corneal reconstruction with tissue-engineered cell sheets composed of autologous oral mucosal epithelium.
N Engl J Med.
2004;
351
1187-1196
-
41
Kruse F, Rohrschneider K, Völcker H E.
Amniotic membrane transplantation for ocular surface reconstruction.
Der Ophthalmologe.
1998;
95 (2)
114-119
-
42
Kruse F, Meller D.
Die Amnionmembrantransplantation zur Rekonstruktion der Augenoberfläche.
Der Ophthalmologe.
2001;
98 (9)
801-810
-
43
Reinhard T, Sundmacher R.
Therapeutische Strategien bei rezidivierender Erosio nach mechanischem Trauma, bei epithelialer Basalmembrandystrophie und idiopathischer Genese.
Der Ophthalmologe.
2000;
97 (2)
157-172
-
44
Meller D, Tseng S CG.
Transplantation of amniotic membrane for conjunctival and corneal surface reconstruction.
Der Ophthalmologe.
1998;
95 (12)
805-813
-
45
Aggarwal S, Pittenger M F.
Human mesenchymal stem cells modulate allogeneic immune cell responses.
Blood.
2005;
105
1815-1822
-
46
Barry F P, Murphy J M, English K. et al .
Immunogenicity of adult mesenchymal stem cells: lessons from the fetal allograft.
Stem Cells Dev.
2005;
14
252-265
-
47
Le Blanc K, Rasmusson I, Sundberg B. et al .
Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells.
Lancet.
2004;
363
1439-1441
Prof. Dr. Burkhard Wiechens
Klinik für Augenheilkunde, Klinikum Region Hannover, Klinikum Nordstadt
Haltenhoffstr. 41
30167 Hannover
Phone: ++ 49/5 11/9 70 12 13
Fax: ++ 49/5 11/9 70 16 43
Email: burkhard.wiechens@krh.eu
