Comparison of Human Placenta- and Bone Marrow–Derived Multipotent Mesenchymal Stem Cells

Abstract

Bone marrow is the traditional source of human multipotent mesenchymal stem cells (MSCs), but placenta appears to be an alternative and more readily available source. This study comprehensively compared human placenta-derived MSC (hpMSC) and human bone marrow-derived MSC (hbmMSC) in terms of cell characteristics, optimal growth conditions and in vivo safety specifically to determine if hpMSC could represent a source of human MSC for clinical trial. MSC were isolated from human placenta (hpMSC) and human bone marrow (hbmMSC) and expanded ex vivo using good manufacturing practice-compliant reagents. hpMSC and hbmMSC showed similar proliferation characteristics in different basal culture media types, fetal calf serum (FCS) concentrations, FCS heat-inactivation experiments, flask types and media replacement responsiveness. However, hpMSC and hbmMSC differed with respect to their proliferation capabilities at different seeding densities, with hbmMSC proliferating more slowly than hpMSC in every experiment. hpMSC had greater long-term growth ability than hbmMSC. MSC from both sources exhibited similar light microscopy morphology, size, cell surface phenotype, and mesodermal differentiation ability with the exception that hpMSC consistently appeared less able to differentiate to the adipogenic lineage. A comparison of both hbmMSC and hpMSC from early and medium passage cultures using single-nucleotide polymorphism (SNP) GeneChip analysis confirmed GTG-banding data that no copy number changes had been acquired during sequential passaging. In three of three informative cases (in which the gender of the delivered baby was male), hpMSC were of maternal origin. Neither hpMSC nor hbmMSC caused any acute toxicity in normal mice when injected intravenously at the same, or higher, doses than those currently used in clinical trials of hbmMSC. This study suggests that human placenta is an acceptable alternative source for human MSC and their use is currently being evaluated in clinical trials.

Isolation and Expansion of Mesenchymal Stem/Stromal Cells Derived from Human Placenta Tissue

“…In contrast to bone marrow aspirates, term placenta is a physically large starting tissue (typically 500-750 g 4 ), which can be harvested aseptically during cesarean section with no risk to the donor. MSC derived from placenta have long-term proliferation 5 and immunomodulatory capacity 6 , superior to bone marrow-derived MSC. In a previous study, we demonstrated that a single term placenta contained sufficient MSC for the manufacture of up to 7,000 clinical doses 4 .…”

Potential of Human Fetal Chorionic Stem Cells for the Treatment of Osteogenesis Imperfecta

“…For example, it is essential to have a source of stem cells that have high therapeutic potential and are easily accessible for clinical use. Extra-embryonic fetal tissues, such as the placenta, are readily available either from termination of pregnancy or surplus tissue at routine prenatal diagnostic procedures [17,18], or at term delivery [19,[20][21][22]. Recently, we have shown human fetal early chorionic stem cells (e-CSC) isolated from human placental tissue accelerated tissue repair in dermal excision skin wounds and improved bone quality and plasticity in oim mice.…”

Multipotent mesenchymal stem cells from human placenta: critical parameters for isolation and maintenance of stemness after isolation

“…10 Mechanical as well as enzymatic methods for MSC isolation from different regions of human placenta of different gestational ages were reported (Table 1, see references therein). 5,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] Knowledge about vitality, karyotype, phenotype and expandability of such placenta-derived MSC isolates is a prerequisite for therapeutic application, however systematic investigations into reliability of this MSC source and phenotypic stability have not yet been attempted. Further, former reports on placenta-derived MSCs often lack information about the karyotype of the cell isolates.…”