Chorion Mesenchymal Stem Cells Show Superior Differentiation, Immunosuppressive, and Angiogenic Potentials in Comparison With Haploidentical Maternal Placental Cells.
Mesenchymal stem cells (MSCs) of placental origin have become increasingly translational owing to their abundance and accessibility. MSCs of different origin share several features but also present biological differences that might point to distinct clinical properties. Hence, mixing fetal and maternal cells from the same placenta can lead to contradicting results. We analyzed the biological characteristics of haploidentical MSCs isolated from fetal sources, including the umbilical cord (UC-MSCs) and chorion (Ch-MSCs), compared with maternal decidua MSCs (Dc-MSCs). All MSCs were analyzed for general stem cell properties. In addition, immunosuppressive capacity was assessed by the inhibition of T-cell proliferation, and angiogenic potential was evaluated in a Matrigel transplantation assay. The comparison between haploidentical MSCs displayed several distinct features, including (a) marked differences in the expression of CD56, (b) a higher proliferative capacity for Dc-MSCs and UC-MSCs than for Ch-MSCs, (c) a diversity of mesodermal differentiation potential in favor of fetal MSCs, (d) a higher capacity for Ch-MSCs to inhibit T-cell proliferation, and (e) superior angiogenic potential of Ch-MSCs evidenced by a higher capability to form tubular vessel-like structures and an enhanced release of hepatocyte growth factor and vascular endothelial growth factor under hypoxic conditions. Our results suggest that assessing the prevalence of fetomaternal contamination within placental MSCs is necessary to increase robustness and limit side effects in their clinical use. Finally, our work presents evidence positioning fetoplacental cells and notably Ch-MSCs in the forefront of the quest for cell types that are superior for applications in regenerative medicine.


CONCLUSIONS
This study analyzed the biological characteristics of mesenchymal stem cells (MSCs) isolated from fetal and maternal placental origins. The findings can be summarized as follows: (a) important differences were found in the expression of CD56, (b) a different mesodermal differentiation potential was found in favor of fetal MSCs, (c) a higher immunosuppressive capacity for chorion MSCs was noted, and (d) superior angiogenic potential of Ch-MSCs was observed. These results suggest that assessing the prevalence of fetomaternal contamination within placental MSCs is necessary to increase robustness and limit side effects in their clinical use. The evidence should allow clinicians to view fetoplacental cells, notably Ch-MSCs, favorably as candidates for use in regenerative medicine.
Laboratory of Nano-Regenerative Medicine, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile; Cells for Cells, Santiago, Chile; Facultad de Medicina Universidad de los Andes y Clínica Universidad de Los Andes, Santiago, Chile; Consorcio Regenero, Santiago, Chile.
Paz L
PL
González
Laboratory of Nano-Regenerative Medicine, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile; Cells for Cells, Santiago, Chile; Facultad de Medicina Universidad de los Andes y Clínica Universidad de Los Andes, Santiago, Chile; Consorcio Regenero, Santiago, Chile.
Catalina
C
Carvajal
Laboratory of Nano-Regenerative Medicine, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile; Cells for Cells, Santiago, Chile; Facultad de Medicina Universidad de los Andes y Clínica Universidad de Los Andes, Santiago, Chile; Consorcio Regenero, Santiago, Chile.
Jimena
J
Cuenca
Laboratory of Nano-Regenerative Medicine, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile; Cells for Cells, Santiago, Chile; Facultad de Medicina Universidad de los Andes y Clínica Universidad de Los Andes, Santiago, Chile; Consorcio Regenero, Santiago, Chile.
Francisca
F
Alcayaga-Miranda
Laboratory of Nano-Regenerative Medicine, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile; Cells for Cells, Santiago, Chile; Facultad de Medicina Universidad de los Andes y Clínica Universidad de Los Andes, Santiago, Chile; Consorcio Regenero, Santiago, Chile.
Fernando E
FE
Figueroa
Laboratory of Nano-Regenerative Medicine, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile; Cells for Cells, Santiago, Chile; Facultad de Medicina Universidad de los Andes y Clínica Universidad de Los Andes, Santiago, Chile; Consorcio Regenero, Santiago, Chile.
Jorge
J
Bartolucci
Laboratory of Nano-Regenerative Medicine, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile; Cells for Cells, Santiago, Chile; Facultad de Medicina Universidad de los Andes y Clínica Universidad de Los Andes, Santiago, Chile; Consorcio Regenero, Santiago, Chile.
Lorena
L
Salazar-Aravena
Laboratory of Nano-Regenerative Medicine, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile; Cells for Cells, Santiago, Chile; Facultad de Medicina Universidad de los Andes y Clínica Universidad de Los Andes, Santiago, Chile; Consorcio Regenero, Santiago, Chile mkhoury@uandes.cl.
Maroun
M
Khoury
D019002:CD56 Antigen / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation; D002478:Cells, Cultured; D002823:Chorion / Q000166:cytology*; D003656:Decidua / Q000166:cytology*; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D005333:Fetus / Q000166:cytology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007165:Immunosuppression Therapy; D007231:Infant, Newborn; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D018919:Neovascularization, Physiologic; D009928:Organ Specificity; D044968:Regenerative Medicine; D013601:T-Lymphocytes / Q000276:immunology
D019002:CD56 Antigen; C522918:NCAM1 protein, human
Angiogenic potential; Chorion; Decidua; Fetal; Immunosuppression; Maternal; Mesenchymal stem cells; Placental cells; Umbilical cord