|
|||||
|
|
Priming human adipose-derived mesenchymal stem cells for corneal surface regeneration |
|
| Authors: | Núria Nieto-Nicolau Eva M Martínez-Conesa Sherezade Fuentes-Julián Francisco Arnalich-Montiel Ignacio García-Tuñón María P De Miguel Ricardo P Casaroli-Marano |
| Institution: | 1. CellTec-UB, Department of Cell Biology, University of Barcelona, Barcelona, Spain
Barcelona Tissue Bank (BTB), Banc de Sang I Teixits (BST), Barcelona, Spain Institute of Biomedical Research IIB-Sant Pau (SGR1113), Barcelona, Spain Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), ?Investigation (equal), Methodology (equal), Validation (equal), Writing - original draft (equal), Writing - review & editing (equal);2. Barcelona Tissue Bank (BTB), Banc de Sang I Teixits (BST), Barcelona, Spain Institute of Biomedical Research IIB-Sant Pau (SGR1113), Barcelona, Spain Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), ?Investigation (equal), Methodology (equal), Validation (equal);3. Cell Engineering Laboratory, La Paz Hospital Research Institute (IdiPAZ), Madrid, Spain Contribution: Formal analysis (equal), ?Investigation (equal), Methodology (equal), Validation (equal);4. Cell Engineering Laboratory, La Paz Hospital Research Institute (IdiPAZ), Madrid, Spain Contribution: Formal analysis (equal), ?Investigation (equal), Validation (equal);5. Cell Engineering Laboratory, La Paz Hospital Research Institute (IdiPAZ), Madrid, Spain Contribution: Conceptualization (equal), Formal analysis (equal), Validation (equal);6. CellTec-UB, Department of Cell Biology, University of Barcelona, Barcelona, Spain |
| Abstract: | Limbal stem cells (LSC) maintain the transparency of the corneal epithelium. Chemical burns lead the loss of LSC inducing an up-regulation of pro-inflammatory and pro-angiogenic factors, triggering corneal neovascularization and blindness. Adipose tissue-derived mesenchymal stem cells (AT-MSC) have shown promise in animal models to treat LSC deficiency (LSCD), but there are not studies showing their efficacy when primed with different media before transplantation. We cultured AT-MSC with standard medium and media used to culture LSC for clinical application. We demonstrated that different media changed the AT-MSC paracrine secretion showing different paracrine effector functions in an in vivo model of chemical burn and in response to a novel in vitro model of corneal inflammation by alkali induction. Treatment of LSCD with AT-MSC changed the angiogenic and inflammatory cytokine profile of mice corneas. AT-MSC cultured with the medium that improved their cytokine secretion, enhanced the anti-angiogenic and anti-inflammatory profile of the treated corneas. Those corneas also presented better outcome in terms of corneal transparency, neovascularization and histologic reconstruction. Priming human AT-MSC with LSC specific medium can potentiate their ability to improve corneal wound healing, decrease neovascularization and inflammation modulating paracrine effector functions in an in vivo optimized rat model of LSCD. |
| Keywords: | cell culture priming cytokines directed differentiation media limbal stem cells limbal stem cells deficiency paracrine secretion |