title: A Comparative Study of the Therapeutic Potential of Mesenchymal Stem Cells and Limbal Epithelial Stem Cells for Ocular Surface Reconstruction.
abstract: Stem cell-based therapy has become an attractive and promising approach for the treatment of severe injuries or thus-far incurable diseases. However, the use of stem cells is often limited by a shortage of available tissue-specific stem cells; therefore, other sources of stem cells are being investigated and tested. In this respect, mesenchymal stromal/stem cells (MSCs) have proven to be a promising stem cell type. In the present study, we prepared MSCs from bone marrow (BM-MSCs) or adipose tissue (Ad-MSCs) as well as limbal epithelial stem cells (LSCs), and their growth, differentiation, and secretory properties were compared. The cells were grown on nanofiber scaffolds and transferred onto the alkali-injured eye in a rabbit model, and their therapeutic potential was characterized. We found that BM-MSCs and tissue-specific LSCs had similar therapeutic effects. Clinical characterization of the healing process, as well as the evaluation of corneal thickness, re-epithelialization, neovascularization, and the suppression of a local inflammatory reaction, were comparable in the BM-MSC- and LSC-treated eyes, but results were significantly better than in injured, untreated eyes or in eyes treated with a nanofiber scaffold alone or with a nanofiber scaffold seeded with Ad-MSCs. Taken together, the results show that BM-MSCs' therapeutic effect on healing of injured corneal surface is comparable to that of tissue-specific LSCs. We suggest that BM-MSCs can be used for ocular surface regeneration in cases when autologous LSCs are absent or difficult to obtain.
  
  
  CONCLUSIONS
  Damage of ocular surface represents one of the most common causes of impaired vision or even blindness. Cell therapy, based on transplantation of stem cells, is an optimal treatment. However, if limbal stem cells (LSCs) are not available, other sources of stem cells are tested. Mesenchymal stem cells (MSCs) are a convenient type of cell for stem cell therapy. The therapeutic potential of LSCs and MSCs was compared in an experimental model of corneal injury, and healing was observed following chemical injury. MSCs and tissue-specific LSCs had similar therapeutic effects. The results suggest that bone marrow-derived MSCs can be used for ocular surface regeneration in cases when autologous LSCs are absent or difficult to obtain.
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic; Faculty of Natural Science, Charles University, Prague, Czech Republic; Czech Technical University in Prague, Faculty of Biomedical Engineering, Kladno, Czech Republic holan@biomed.cas.cz.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Holan
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic; Faculty of Natural Science, Charles University, Prague, Czech Republic; Czech Technical University in Prague, Faculty of Biomedical Engineering, Kladno, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Trosan
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic; Faculty of Natural Science, Charles University, Prague, Czech Republic; Czech Technical University in Prague, Faculty of Biomedical Engineering, Kladno, Czech Republic.
authors.forename: Cestmir
authors.initials: C
authors.lastname: Cejka
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic; Faculty of Natural Science, Charles University, Prague, Czech Republic; Czech Technical University in Prague, Faculty of Biomedical Engineering, Kladno, Czech Republic.
authors.forename: Eliska
authors.initials: E
authors.lastname: Javorkova
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic; Faculty of Natural Science, Charles University, Prague, Czech Republic; Czech Technical University in Prague, Faculty of Biomedical Engineering, Kladno, Czech Republic.
authors.forename: Alena
authors.initials: A
authors.lastname: Zajicova
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic; Faculty of Natural Science, Charles University, Prague, Czech Republic; Czech Technical University in Prague, Faculty of Biomedical Engineering, Kladno, Czech Republic.
authors.forename: Barbora
authors.initials: B
authors.lastname: Hermankova
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic; Faculty of Natural Science, Charles University, Prague, Czech Republic; Czech Technical University in Prague, Faculty of Biomedical Engineering, Kladno, Czech Republic.
authors.forename: Milada
authors.initials: M
authors.lastname: Chudickova
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic; Faculty of Natural Science, Charles University, Prague, Czech Republic; Czech Technical University in Prague, Faculty of Biomedical Engineering, Kladno, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Cejkova
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000502:physiology; D000273:Adipose Tissue / Q000166:cytology / Q000502:physiology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D002057:Burns, Chemical / Q000473:pathology / Q000628:therapy*; D002454:Cell Differentiation; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology* / Q000637:transplantation; D019573:Epithelium, Corneal / Q000098:blood supply / Q000293:injuries*; D005260:Female; D015870:Gene Expression; D016850:Limbus Corneae / Q000098:blood supply / Q000293:injuries*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D018919:Neovascularization, Physiologic; D061251:Primary Cell Culture; D011817:Rabbits; D062326:Re-Epithelialization / Q000502:physiology; D054457:Tissue Scaffolds
chemical_list: D015415:Biomarkers
keywords: Alkali-injured ocular surface; Corneal regeneration; Limbal stem cells; Mesenchymal stem cells; Stem cell-based therapy