Faculty Collaboration Database

Human embryonic stem cell-derived mesenchymal stromal cell transplantation in a rat hind limb injury model. Cytotherapy 2009;11(6):726-37

Date

11/03/2009

Pubmed ID

19878059

Pubmed Central ID

PMC2889035

DOI

10.3109/14653240903067299

Scopus ID

2-s2.0-73649115624 (requires institutional sign-in at Scopus site)   59 Citations

Abstract

BACKGROUND AIMS: Mesenchymal stromal cells (MSC) have been used in a wide variety of pre-clinical experiments and in an increasing number of human clinical trials. Although many of these studies have shown different levels of engraftment, the exact fate of MSC after transplantation and the tissue response to their engraftment have not been investigated in detail. In the present work we studied the distribution of human MSC in a rat hind limb ischemic injury model immediately after transplantation and also analyzed the recipient tissue response to transplanted cells.

METHODS: We tracked the in vivo fate of the transplanted MSC utilizing bioluminescence imaging, fluorescence microscopy and gene/protein expression analysis in a rat hind limb ischemia model. We also monitored the viability of transplanted cells by graft versus recipient expression analysis and determined the angiogenic and proliferative effect of transplantation by histologic staining.

RESULTS: According to imaging analysis only a small portion of cells persisted for an extended period of time at the site of injury. Interestingly, recipient versus graft expression studies showed increased synthesis of rat-origin angiogenic factors and no human-origin mRNA or protein synthesis in transplanted tissues. More importantly, despite the lack of robust engraftment or growth factor secretion the transplantation procedure exerted a significant pro-angiogenic and pro-proliferative effect, which was mediated by angiogenic and mitogenic signaling pathways.

CONCLUSIONS: Our results show an immediate temporal tissue effect in response to MSC transplantation that may represent a novel indirect paracrine mechanism for the beneficial effects of cell transplantation observed in injured tissues.

Author List

Laurila JP, Laatikainen L, Castellone MD, Trivedi P, Heikkila J, Hinkkanen A, Hematti P, Laukkanen MO

Author

Peiman Hematti MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cell Differentiation
Cell Proliferation
Disease Models, Animal
Embryonic Stem Cells
Gene Expression
Graft vs Host Reaction
Host vs Graft Reaction
Humans
Lower Extremity
Male
Mesenchymal Stem Cell Transplantation
Neovascularization, Physiologic
Rats
Regeneration
Reperfusion Injury
Signal Transduction
Transduction, Genetic
Vascular Endothelial Growth Factor A