IADR Abstract Archives
Safety Profile of Human Endothelial Progenitor Cells
Objectives: In order to pave the way toward first in man study using autologous blood derived human endothelial progenitor cells (hEPC), this study aims to evaluate the safety profile of hEPC.
Methods: Primary hEPCs were isolated, cultured and characterized from seven volunteers. In order to ensure DNA stability, karyotype of hEPCs was analyzed in passages 4-7.Biodistribution of the cells was evaluated following local or systemic hEPCs administration. Local transplantation was tested in guided bone regeneration calvaria model; βTCP scaffold mixed with 106 hEPC (n=6) or βTCP without cells (n=6) were transplanted under gold domes that were fixed to nude rat calvaria. Systemic administration included injection of 108/kg hEPC into the tail vein of 2 SCID mice. At 5 month, blood was drawn for complete blood count (CBC) analysis. Thereafter, animals were sacrificed and target organs were scanned for pathological changes. Immunohistochimestry was used to identify cell migration to target organs using human CD31 and KI67.
Results: DNA analysis of expanded hEPCs showed normal kariotype. Animals in both in-vivo models gained weight and display normal behavior during the five months follow-up period. CBC values were within normal ranges. Target organs collected from rats that were treated with local hEPCs transplantation were intact without any macroscopic signs for abnormal tissue growth. Histo-pathological examination of the target organs showed normal morphology in all the slides therefore excluding the presence of a-typical cellular aggregations or pathologic tissue growth. Furthermore, all samples were negative for CD31 and KI67. Nevertheless, histological analysis of target organs obtained from mice treated with intravenous injection of hEPCs displayed micro-calcifications on the pericardium of one mouse
Conclusions: Pathological conditions were neither observed in the DNA of the cells nor in the target organs of rats treated with local hEPC transplantation. The occurrence of pericardial micro-calcification following systemic injection of hEPCs requires additional investigations
Methods: Primary hEPCs were isolated, cultured and characterized from seven volunteers. In order to ensure DNA stability, karyotype of hEPCs was analyzed in passages 4-7.Biodistribution of the cells was evaluated following local or systemic hEPCs administration. Local transplantation was tested in guided bone regeneration calvaria model; βTCP scaffold mixed with 106 hEPC (n=6) or βTCP without cells (n=6) were transplanted under gold domes that were fixed to nude rat calvaria. Systemic administration included injection of 108/kg hEPC into the tail vein of 2 SCID mice. At 5 month, blood was drawn for complete blood count (CBC) analysis. Thereafter, animals were sacrificed and target organs were scanned for pathological changes. Immunohistochimestry was used to identify cell migration to target organs using human CD31 and KI67.
Results: DNA analysis of expanded hEPCs showed normal kariotype. Animals in both in-vivo models gained weight and display normal behavior during the five months follow-up period. CBC values were within normal ranges. Target organs collected from rats that were treated with local hEPCs transplantation were intact without any macroscopic signs for abnormal tissue growth. Histo-pathological examination of the target organs showed normal morphology in all the slides therefore excluding the presence of a-typical cellular aggregations or pathologic tissue growth. Furthermore, all samples were negative for CD31 and KI67. Nevertheless, histological analysis of target organs obtained from mice treated with intravenous injection of hEPCs displayed micro-calcifications on the pericardium of one mouse
Conclusions: Pathological conditions were neither observed in the DNA of the cells nor in the target organs of rats treated with local hEPC transplantation. The occurrence of pericardial micro-calcification following systemic injection of hEPCs requires additional investigations