Placenta as a newly identified source of hematopoietic stem cells

Department of Obstetrics and Gynecology, University of California, Los Angeles, Los Angeles, California 90095, USA.
Current opinion in hematology (Impact Factor: 3.97). 07/2010; 17(4):313-8. DOI: 10.1097/MOH.0b013e328339f295
Source: PubMed


The lifelong stream of all blood cells originates from the pool of hematopoietic stem cells (HSCs) generated during embryogenesis. Given that the placenta has been recently unveiled as a major hematopoietic organ that supports HSC development, the purpose of this review is to present current advances in defining the origin and regulation of placental HSCs.
The mouse placenta has been shown to have the potential to generate multipotential myelo-lymphoid hematopoietic stem/progenitor cells de novo. The cellular origin of HSCs generated in the placenta and other sites has been tracked to the hemogenic endothelium by using novel genetic and imaging-based cell-tracing approaches. Transplantable, myelo-lymphoid hematopoietic stem/progenitor cells have also been recovered from the human placenta throughout gestation.
The discovery of the placenta as a major organ that generates HSCs and maintains them in an undifferentiated state provides a valuable model to further elucidate regulatory mechanisms governing HSC emergence and expansion during mouse and human development. Concurrent efforts to optimize protocols for placental banking and HSC harvesting may increase the therapeutic utility of the human placenta as a source of transplantable HSCs.

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Available from: Ben Van Handel, Jul 03, 2014
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    • "Primitive hematopoiesis is transient and does not involve transplantable hematopoietic stem cells (HSCs) (Cumano et al. 1996, 2001). Primitive hematopoiesis is replaced by ''definitive'' hematopoiesis, in which transplantable HSCs arise around E8.5 intraembryonically (Medvinsky and Dzierzak 1996; Sanchez et al. 1996; Cumano et al. 2001), as well as potentially within the yolk sac (Weissman et al. 1978; Yoder et al. 1997; Samokhvalov et al. 2007) and placenta (Gekas et al. 2005; Lee et al. 2010). These HSCs migrate into the fetal liver where they establish definitive hematopoiesis that endures throughout the rest of gestation. "
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    ABSTRACT: A key question concerns the mechanisms that determine temporal identity in stem cells. Fetal hematopoietic stem cells (HSCs) differ from adult HSCs in terms of gene expression profile, surface marker expression, differentiation, and self-renewal capacity. We previously showed that the transcription factor SOX17 is expressed by fetal, but not adult, HSCs and is required for the maintenance of fetal and neonatal, but not adult, HSCs. In the current study, we show that ectopic expression of Sox17 in adult HSCs and transiently reconstituting multipotent progenitors was sufficient to confer increased self-renewal potential and the expression of fetal HSC genes, including fetal HSC surface markers. Sox17 expression enabled transiently reconstituting adult progenitors to give long-term multilineage reconstitution that resembled fetal hematopoiesis, including increased erythropoiesis, increased myelopoiesis, and decreased lymphopoiesis. Long-term ectopic expression of Sox17 eventually led to leukemogenesis. These data demonstrate that SOX17 is sufficient to confer fetal HSC characteristics to adult hematopoietic progenitors and is therefore a key determinant of fetal HSC identity.
    Genes & development 08/2011; 25(15):1613-27. DOI:10.1101/gad.2052911 · 10.80 Impact Factor
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    • "HSCs can be isolated from bone marrow, peripheral blood, umbilical cord blood [34], and a newly identified source, placenta [35]. HSCs are multipotent and capable of differentiating into multiple hematopoietic lineages, including erythroid (blood cells), myeloid (leukocyte), and lymphoid (lymphocyte) [36]. "
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    ABSTRACT: Enhancer of zeste homolog 2 (EZH2), a catalytic component of polycomb repressive complex 2 (PRC2), epigenetically regulates chromatin structure and gene expressions through tri-methylation at histone H3K27 and recruitment of DNA methyltransferases for gene silencing. Despite extensive studies of the role of EZH2 in cancer progression and malignancy, increasing evidence also suggest that EZH2 plays a critical role in stem cells renewal, maintenance, and differentiation into specific cell lineages. Here, we review the updated information regarding how EZH2 contributes to stem cell maintenance, cell lineage determination, including myogenesis, adipogenesis, osteogenesis, neurogenesis, hematopoiesis, lymphopoiesis, epidermal differentiation and hepatogenesis, and how EZH2 is regulated by phosphorylation and microRNAs in these processes.
    American Journal of Translational Research 05/2011; 3(3):243-50. · 3.40 Impact Factor
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    ABSTRACT: Mesenchymal stem cells (MSC) have been used in clinical trials for severe diabetes, a chronic disease with high morbidity and mortality. Bone marrow is the traditional source of human MSC, but human term placenta appears to be an alternative and more readily available source. Here, the therapeutic effect of human placenta-derived MSC (PD-MSC) was studied in type 2 diabetes patients with longer duration, islet cell dysfunction, high insulin doses as well as poor glycemic control in order to evaluate the safety, efficacy and feasibility of PDMSC treatment in type 2 diabetes (T2D). Ten patients with T2D received three intravenous infusions of PDSC, with one month interval of infusion. The total number of PDSC for each patient was (1.22-1.51) × 10(6)/kg, with an average of 1.35 × 10(6)/kg. All of the patients were followed up after therapy for at least 3 months. A daily mean dose of insulin used in 10 patients was decreased from 63.7±18.7 to 34.7±13.4 IU (P<0.01), and the C-peptide level was increased from 4.1 ±3.7 ng/mL to 5.6 ±3.8 ng/mL (P<0.05) respectively after therapy. In 4 of 10 responders their insulin doses reduced more than 50% after infusion. The mean levels of insulin and C-peptide at each time point in a total of 10 patients was higher after treatment (P<0.05). No fever, chills, liver damage and other side effects were reported. The renal function and cardiac function were improved after infusion. The results obtained from this pilot clinical trial indicate that transplantation of PD-MSC represents a simple, safe and effective therapeutic approach for T2D patients with islet cell dysfunction. Further large-scale, randomized and well-controlled clinical studies will be required to substantiate these observations.
    Frontiers of Medicine 03/2011; 5(1):94-100. DOI:10.1007/s11684-011-0116-z
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