We have identified a subpopulation of stem cells within adult human BM, isolated at the single-cell level, that self-renew without loss of multipotency for more than 140 population doublings and exhibit the capacity for differentiation into cells of all 3 germ layers. Based on surface marker expression, these clonally expanded human BM-derived multipotent stem cells (hBMSCs) do not appear to belong to any previously described BM-derived stem cell population. Intramyocardial transplantation of hBMSCs after myocardial infarction resulted in robust engraftment of transplanted cells, which exhibited colocalization with markers of cardiomyocyte (CMC), EC, and smooth muscle cell (SMC) identity, consistent with differentiation of hBMSCs into multiple lineages in vivo. Furthermore, upregulation of paracrine factors including angiogenic cytokines and antiapoptotic factors, and proliferation of host ECs and CMCs, were observed in the hBMSC-transplanted hearts. Coculture of hBMSCs with CMCs, ECs, or SMCs revealed that phenotypic changes of hBMSCs result from both differentiation and fusion. Collectively, the favorable effect of hBMSC transplantation after myocardial infarction appears to be due to augmentation of proliferation and preservation of host myocardial tissues as well as differentiation of hBMSCs for tissue regeneration and repair. To our knowledge, this is the first demonstration that a specific population of multipotent human BM-derived stem cells can induce both therapeutic neovascularization and endogenous and exogenous cardiomyogenesis.

Fetal cells enter the maternal circulation during all pregnancies.^1,2 They can persist in maternal blood or tissues for decades, creating a state of physiologic microchimerism in the parous woman.³ Recent studies detected male cells of presumed fetal origin in 30% to 50% of healthy women who had prior male pregnancies.⁴ The long-term consequences of fetal cell microchimerism for maternal health are only beginning to be appreciated. Fetal microchimeric cells are present in higher numbers in women with some autoimmune diseases, such as systemic sclerosis, than in control groups.^5,6 We have also observed fetal cells in the tissues of women with nonautoimmune disorders, such as hepatitis C⁷ and cervical cancer.⁸ Thus, we developed an alternate hypothesis in which fetal cells were associated with the maternal response to injury as opposed to causing disease.

Placenta-derived stem cells (PDSCs) have gained interest as an alternative source of stem cells for regenerative medicine because of their potential for self-renewal and differentiation and their immunomodulatory properties. Although many studies have characterized various PDSCs biologically, the properties of the self-renewal and differentiation potential among PDSCs have not yet been directly compared. We consider the characterization of chorionic-plate-derived mesenchymal stem cells (CP-MSCs) and Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) among various PDSCs and the assessment of their differentiation potential to be important for future studies into the applicability and effectiveness of PDSCs in cell therapy. In the present study, the capacities for self-renewal and multipotent differentiation of CP-MSCs and WJ-MSC isolated from normal term placentas were compared. CP-MSCs and WJ-MSCs expressed mRNAs for the pluripotent stem cell markers Oct-4, Nanog, and Sox-2. Additionally, HLA-G for immunomodulatory effects was found to be expressed at both the mRNA and protein levels in both cell types. The CP-MSCs and WJ-MSCs also had the capacities to differentiate into cells of mesodermal (adipogenic and osteogenic) and endodermal (hepatogenic) lineages. Expression of adipogenesis-related genes was higher in CP-MSCs than in WJ-MSCs, whereas WJ-MSCs accumulated more mineralized matrix than CP-MSCs. The WJ-MSCs expressed more of CYP3A4 mRNA, a marker for mature hepatocytes, than CP-MSCs. Thus, we propose that CP-MSCs and WJ-MSCs are useful sources of cells for appropriate clinical applications in the treatment of various degenerative diseases.

Objective: Fetal cells enter the maternal circulation during most pregnancies. Their persistence for years occurs in only some women and has been associated with several autoimmune diseases such as systemic sclerosis. The objective of this study was to determine whether pregnancy history influences the persistence of fetal microchimeric cells.Methods: We reviewed all reports of studies on fetal cell microchimerism, defined as male DNA in maternal tissue, that describe individual pregnancy histories, disease diagnoses, and microchimerism status. The total numbers of pregnancies, births, and sons, the history of fetal loss (spontaneous abortion and elective termination), and the presence of a maternal autoimmune disease were tested as factors potentially associated with persistent microchimerism.Results: One hundred twenty‐four subjects from 11 studies met the inclusion criteria. Only fetal loss was significantly associated with the presence of microchimerism (odds ratio 2.4, 95% confidence interval 1.2–6.0).Conclusion: These results suggest that fetomaternal cell trafficking following fetal loss may be important for the engraftment of microchimeric cells in maternal tissue. This may be due to an increased amount of fetomaternal transfusion or to transfer of a cell type that is more likely to engraft. We recommend that investigators in future studies on microchimerism report detailed pregnancy information, since these data are critical for the understanding of factors that influence the development of fetal cell microchimerism.

To determine whether microchimerism is involved in the pathogenesis or progression of cervical cancer. Cervical tissue was obtained from eight women who had at least one live-born son and who underwent radical hysterectomy after a diagnosis of cervical cancer. Control tissue was obtained from four women without cervical cancer who had at least one live-born son and from three women with cervical cancer and no male births. Tissue sections were analyzed with fluorescence in situ hybridization for the presence of fetal cells, defined by an X and Y chromosome. Immunolabeling was used to determine the phenotype of the presumed fetal cells. Male cells were found in cervical tissue from all four patients for whom large sections (approximately 1.5 x 2 cm) were analyzed. Only one male cell was found in two of the four patients for whom small biopsy specimens (approximately 0.1 x 0.5 cm) were analyzed. No male cells were found in tissue specimens from controls, whether they were small or large sections. In immunolabeling studies, eight of 18 male cells from one patient were CD45-positive and nine of 37 male cells from two patients were cytokeratin-positive. No cells were positive for both markers. Cervical cancer might be associated with microchimerism, possibly from fetomaternal cell trafficking. These results further expand the potential relationship between microchimerism and disease in women.

Although the precise pathophysiology of pre-eclampsia remains unknown, this condition continues to be a major cause of maternal and fetal mortality. Early prediction of pre-eclampsia would allow for timely initiation of preventive therapy. A combination of biophysical and biochemical markers are superior to other tests for early prediction of the development of pre-eclampsia. Apart from the use of parameters in first-trimester aneuploidy screening, cell-free fetal DNA quantification is emerging as a promising marker for prediction of pre-eclampsia. This article reviews the current research of the most important strategies for prediction of pre-eclampsia, including the use of maternal risk factors, mean maternal arterial pressure, ultrasound parameters, and biomarkers.