title: Stem Cells are mobilized from the bone marrow into the peripheral circulation in response to retinal pigment epithelium damage--a pathophysiological attempt to induce endogenous regeneration.
abstract: OBJECTIVE
  Stem cell regeneration of damaged tissue has recently been reported in many different organs. Here, we investigated the mobilization of different stem/progenitor cell (SPC) populations into the peripheral blood (PB), their subsequent homing to the injured retina (IR) and contribution to its regeneration in a retinal pigment epithelium (RPE) damage model induced by sodium iodate (NaIO(3)).
  
  
  METHODS
  Mobilization of SPCs was evaluated by flow cytometry. SPCs distribution in IR was assessed using bone marrow (BM)-derived GFP(+)Lin(-) cells transplanted intravenously into NaIO(3)-treated C57Bl/6 mice. The quantity of the chemokine SDF-1 in PB and IR was measured by ELISA and qRT-PCR, respectively. Apoptosis (TUNEL assay), cell proliferation (PCNA analysis) as well as functional retinal activity (electroretinogram) were examined at several time points after NaIO(3) administration.
  
  
  RESULTS
  Mobilization of SPCs along with the highest cell proliferation and massive apoptosis within IR were observed on the third day after NaIO(3) administration. Similarly, donor GFP(+)Lin(-) cells were detected in the retina as soon as day 4 after NaIO(3) injection. Plasma levels of SDF-1 did not differ significantly in mice exposed to NaIO(3) compared to healthy controls, however mRNA for SDF-1 was overexpressed locally in IR. Functional retinal recovery was not achieved.
  
  
  CONCLUSIONS
  Our study provides evidence that BM SPCs egress into PB and home to the injured retina, but are not capable of restoring its function. These results indicate that if the range of retinal destruction is profound, endogenous regeneration is ineffective and may ultimately require adjuvant therapeutic transplantation of specific SPCs subpopulations.
authors.affiliation: Department of Histology and Embryology, Pomeranian Medical University, Szczecin, Poland. annam@sci.pam.szczecin.pl
authors.forename: Anna
authors.initials: A
authors.lastname: Machalińska
authors.forename: Patrycja
authors.initials: P
authors.lastname: Kłos
authors.forename: Bartłomiej
authors.initials: B
authors.lastname: Baumert
authors.forename: Magdalena
authors.initials: M
authors.lastname: Baśkiewicz
authors.forename: Miłosz
authors.initials: M
authors.lastname: Kawa
authors.forename: Michał
authors.initials: M
authors.lastname: Rudnicki
authors.forename: Wojciech
authors.initials: W
authors.lastname: Lubiński
authors.forename: Barbara
authors.initials: B
authors.lastname: Wiszniewska
authors.forename: Danuta
authors.initials: D
authors.lastname: Karczewicz
authors.forename: Bogusław
authors.initials: B
authors.lastname: Machaliński
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D017209:Apoptosis; D001775:Blood Circulation / Q000502:physiology; D001854:Bone Marrow Cells / Q000502:physiology*; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D020287:In Situ Nick-End Labeling; D007452:Iodates / Q000633:toxicity; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012038:Regeneration / Q000502:physiology*; D012162:Retinal Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000950:Antigens, Ly; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D007452:Iodates; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D017493:Leukocyte Common Antigens; C032285:sodium iodate