Hematogenous Donor Cell Routing Pathway After Transamniotic Stem Cell Therapy
- 15 June 2020
- journal article
- research article
- Published by Mary Ann Liebert Inc in Stem Cells and Development
- Vol. 29 (12), 755-760
- https://doi.org/10.1089/scd.2020.0012
Abstract
Donor mesenchymal stem cells (MSCs) have been documented in fetal and maternal circulations after plain intra-amniotic injection, with diverse therapeutic effects. We sought to determine the pathway of this unique cell kinetic route. Rat fetuses (n = 226) were divided into two groups based on the content of intra-amniotic injections performed on gestational day 17 (E17): either a concentrated suspension of luciferase-labeled syngeneic amniotic fluid-derived MSCs (afMSCs; n = 111), or acellular luciferase (n = 115). Samples from placenta, chorion, amnion, amniotic fluid, stomach fluid, peripheral blood, and umbilical cord were procured at five daily time points thereafter until term (E18-22) for luminometry. In addition, 53 sets of fresh gestational membranes (chorion/amnion combined) from nonmanipulated term fetuses were secured to transwell inserts for in vitro analysis of MSC migration using luciferase-labeled afMSCs. Statistical analyses included the Mann-Whitney U-test, Wald test, nonlinear regression modeling, and Fisher's exact test. In vivo, luciferase activity was observed in the amnion, chorion, and placenta of fetuses receiving cells, but not in those receiving acellular luciferase (P < 0.001). There was a consistent nonlinear age-dependent relationship of luciferase activity between the amnion, chorion, and placenta following a parabolic bimodal pattern characterized by significantly higher early preterm (E18) and late-term (E22) activities (P < 0.001), with no differences between E21 and E22 (P = 0.12). In vitro, the presence of cells was documented by luminometry in 21/53 (39.6%) of the assays, in suspension and/or attached to the plastic substrate, and within all screened gestational membrane sets, irrespective of stimuli with collagen coating or fetal bovine serum. We conclude that, after intra-amniotic injection, donor MSCs undergo controlled cell routing, as opposed to passive clearance. Transgestational membrane transport appears to constitute the path for donor cells to reach the placenta, a known gateway to the fetal circulation, significantly expanding the potential applications of transamniotic stem cell therapy.This publication has 28 references indexed in Scilit:
- Amniotic Mesenchymal Stem Cells Enhance Normal Fetal Wound HealingStem Cells and Development, 2011
- Amniotic and Placental Mesenchymal Stem Cell Isolation and CultureMethods in molecular biology (Clifton, N.J.), 2011
- Engraftment, Differentiation, and Functional Benefits of Autologous Cardiosphere-Derived Cells in Porcine Ischemic CardiomyopathyCirculation, 2009
- C3a and C5a Are Chemotactic Factors for Human Mesenchymal Stem Cells, Which Cause Prolonged ERK1/2 PhosphorylationThe Journal of Immunology, 2009
- A new role of substance P as an injury-inducible messenger for mobilization of CD29+ stromal-like cellsNature Medicine, 2009
- Trafficking and differentiation of mesenchymal stem cellsJournal of Cellular Biochemistry, 2009
- Trafficking of Multipotent Mesenchymal Stromal Cells from Maternal Circulation Through the Placenta Involves Vascular Endothelial Growth Factor Receptor-1 and IntegrinsThe International Journal of Cell Cloning, 2007
- Amniotic fluid and placental stem cellsBest Practice & Research Clinical Obstetrics & Gynaecology, 2004
- Haemoglobin interferes with the ex vivo luciferase luminescence assay: consequence for detection of luciferase reporter gene expression in vivoGene Therapy, 2000
- Studies of Mesenchymal Cells from 1st Trimester Human Placenta: Expression of Cytokeratin Outside the Trophoblast LineagePlacenta, 1999