A New Role for the Human Placenta as a Hematopoietic Site Throughout Gestation

Abstract

We investigated whether the human placenta plays a role in embryonic and fetal hematopoietic development. Two cell populations—CD34++CD45low and CD34+CD45low—were found in chorionic villi. CD34++CD45low cells display many markers that are characteristic of multipotent primitive hematopoietic progenitors and hematopoietic stem cells (HSCs). Clonogenic in vitro assays showed that CD34++CD45low cells contained colony-forming units-culture (CFU-C) with myeloid and erythroid potential and differentiated into CD56+ NK cells and CD19+ B cells in culture. CD34+CD45low cells were mostly enriched in erythroid- and myeloid-committed progenitors. The number of CD34++CD45low cells increased throughout gestation in parallel with placental mass. However, their density (cells per gram of tissue) reached its peak at 5–8 weeks, decreasing more than sevenfold from the ninth week onward. In addition to multipotent progenitors, the placenta contained intermediate progenitors, indicative of active hematopoiesis. Together, these data suggest that the human placenta is potentially an important hematopoietic organ, opening the possibility of banking placental HSCs along with cord blood for transplantation.

The human chorion contains definitive hematopoietic stem cells from the fifteenth week of gestation

“…These data show that the density of CD34 ++ CD45 low cells was highest in the first trimester, whereas absolute numbers were highest at term. These findings are in line with our previous observations in chorionic villi of the human placenta (Barcena et al, 2009). …”

“…S1C,E). The three tissues analyzed from first trimester samples were not subjected to any further processing after the enzymatic digestion of the tissues as described (Barcena et al, 2009), whereas second and third trimester tissues were processed further to obtain the light-density fraction. Fig.…”

“…Most of these cells are Hofbauer cells, i.e. CD14 + macrophages, which represent the most abundant mature hematopoietic cells in extraembryonic tissues (Barcena et al, 2009). …”

“…The placenta, which develops in advance of the embryo/fetus to support its growth, was shown to be a hematopoietic organ in mice (Gekas et al, 2005;Ottersbach and Dzierzak, 2005) and humans (Barcena et al, 2009(Barcena et al, , 2011Robin et al, 2009;Serikov et al, 2009). The placenta is composed of highly vascularized tree-like chorionic villi that sprout from the chorionic plate (CP) ( Fig.…”

Hematopoietic Stem Cell Development in the Placenta

“…In-vitro stroma co-culture assays Melchers 1979 Multipotent hematopoietic cells, suggestive of HSCs, were found in the avian allantois Chick-to-quail grafting experiments Caprioli et al 1998Caprioli et al , 2001 Multipotent hematopoietic progenitors of fetal origin were found in the mouse placenta (E9.0 onwards), prior to the fetal liver CD41+ hematopoietic cells are generated autonomously from precirculation allantois Allantois explant culture Corbel et al 2007 The placenta was shown to be capable of de novo generation of multipotent myelo-lymphoid hematopoietic progenitors independent of blood flow Localization of HS/PCs in Runx1-LacZ embryos, in vitro stroma co-culture assays using Ncx1−/− heartbeat mutant embryos Rhodes et al 2008 The human placenta was shown to harbor myelolymphoid hematopoietic progenitors Colony-forming assay and stroma co-culture Barcena et al 2009a The human placenta was shown to harbor myelolymphoid hematopoietic progenitors throughout gestation Colony-forming assay and stroma co-culture Barcena et al 2009b The human placenta was shown to harbor HSCs that were engraftable to immunodeficient mice Transplantation of human placental tissues to NOD-SCID and Rag2−/−γC−/− mice Robin et al 2009 …”