Artificial Hematopoietic Stem Cell Niche Sustains Growth and Differentiation of Human ES-Derived Early Hematopoietic Progenitors.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1415-1415
Author(s):  
Babak Esmaeli-Azad ◽  
Anand S. Srivastava ◽  
Cybele Frederico ◽  
Geraldo Martinez ◽  
Satoshi Yasukawa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell Niche ◽  
High Efficiency ◽  
Es Cells ◽  
Embryonic Stem ◽  
Hematopoietic Progenitors ◽  
Hematopoietic Stem ◽  
Hematopoietic Stem Cell Niche ◽  
Human Es Cells ◽  
Cell Niche

Abstract Using a novel Microplate Biomaterial Microarray (MBM™) technology, we have created an artificial hematopoietic stem cell niche that can sustain growth and differentiation of human embryonic stem cells-derived (hES) early hematopoietic progenitors. This hydrogel based ex-vivo niche allows uploading of human embryonal stem cells, human mesenchymal stem cells (MSC), genes (bcl-2 preventing apoptosis and HoxB4 enhancing hematopoiesis) and extracellular matrices to support growth and differentiation of human ES cells. These experiments were done using NIH-approved hES cell lines H1 and H9. Serum-free, feeder-free culture conditions were established and early hematopoietic progenitors grown using SCF, TPO, VEGF and IL-3 with high efficiency. At day 3–5 dual CD34+/CD31+ progenitors were identified, while on day 7–8 CD34+ hematopoietic progenitors were isolated, which formed typical hematopoietic colonies. These progenitors expressed genes related to early hematopoiesis, such as TAL1/SCL, FLT1, GATA2, GATA1, EPOR and TPOR. The early dual endothelio-hematopoietic progenitor (hemangioblast) expressed PECAM-1 and CD34 and showed typical blast-like morphology. Based on mathematical simulations, various micro-niches were designed to establish optimal differentiation conditions for this progenitor using IL-3, IL-6, TPO, EPO, VEGF, SFC, Flt-3 ligand and various extracellular matrices. Specific micro-niches were created for generation of CFU-E, BFU-E, CFU-GM, CFU-GEMM, CFU-M, CFU-G, and CFU-MK progenitors from human ES-derived hemangioblast. Kinetic uploading of TPO, EPO, SCF and VEGF created a niche-sustaining growth of ES-derived hemangioblast with high efficiency and low apoptosis rate. These niches used pulse -delivery of anti-apoptotic bcl-2 gene and hematopoiesis-enhancing Hoxb4 gene. The model of artifical niche sustaing growth and differentiation of human ES-derived hemangioblast was established. In the future, this system will allow optimized and upscaled generation of early hematopoietic progenitors from human ES cells, as a first step towards clinical applications of human embryonic stem cells. Figure Figure

2011 - ENGINEERING A HEMATOPOIETIC STEM CELL NICHE BY REVITALIZING MESENCHYMAL STEM CELLS

2019 ◽  
Vol 76 ◽  
pp. S45
Author(s):  
Fumio Nakahara ◽  
Daniel Borger ◽  
Qiaozhi Wei ◽  
Sandra Pinho ◽  
Maria Maryanovich ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Stem Cell Niche ◽  
Hematopoietic Stem ◽  
Hematopoietic Stem Cell Niche ◽  
Cell Niche

scholarly journals Paracrine Molecules of Mesenchymal Stem Cells for Hematopoietic Stem Cell Niche

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Tian Li ◽  
Yaojiong Wu
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell Niche ◽  
Adult Stem Cells ◽  
Bone Marrow Mscs ◽  
Hematopoietic Stem ◽  
Hematopoietic Stem Cell Niche ◽  
Hsc Niche ◽  
Cell Niche ◽  
Hsc Transplantation

Hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are both adult stem cells residing in the bone marrow. MSCs interact with HSCs, they stimulate and enhance the proliferation of HSCs by secreting regulatory molecules and cytokines, providing a specialized microenvironment for controlling the process of hematopoiesis. In this paper we discuss how MSCs contribute to HSC niche, maintain the stemness and proliferation of HSCs, and support HSC transplantation.

Matrix Glycoprotein Osteopontin Is a Stem Cell Niche Constituent That Constrains the Hematopoietic Stem Cell Pool Size.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 664-664 ◽  
Author(s):  
Sebastian Stier ◽  
Yon Ko ◽  
Randolf Forkert ◽  
Christoph Lutz ◽  
Thomas Neuhaus ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Stem Cell Niche ◽  
Wild Type ◽  
Hematopoietic Stem ◽  
Hematopoietic Stem Cell Niche ◽  
Cell Niche ◽  
Stem Cell Pool

Abstract Stem cells reside in a physical niche where a balance of signals controls their growth, differentiation and death. Niche components have generally been defined in terms of cells and positive effects on stem cell maintenance or expansion. Here we define a role for a matrix glycoprotein that provides a constraining function in the hematopoietic stem cell niche. Osteopontin (OPN) is an abundant glycoprotein in bone that can function as either cytokine or cell adhesion mediator. It is known to be produced by multiple cells types including osteoblasts, cells recently defined to be a regulatory component of the hematopoietic stem cell niche. Using studies combining OPN deficient mice and exogenous OPN, we demonstrate that OPN modifies primitive hematopoietic cell numbers and function. In OPN deficient mice, increased primitive cell numbers were observed in vivo associated with reduced progenitors and reduced primitive cell apoptotic fraction. To determine whether the effect of OPN deficiency was stroma dependent, we performed in vitro stem cell assays on OPN−/− stroma and observed greater LTC-IC supportive capacity compared with wild type stroma. Furthermore, OPN−/− recipients showed a significantly higher proportion of hematopoietic stem cells after transplantation of OPN+/+ bone marrow in comparison to wild-type recipients, indicating that the OPN null microenvironment was sufficient to increase stem cell number. A reduction in apoptotic fraction was seen in primitive cells in the OPN−/− recipient marrows. A role for OPN in apoptosis was confirmed by exogenous OPN in in-vitro studies. Hypothesizing that OPN may serve as a physiologic constraint on stem cell pool size, we compared OPN−/− with wild type animals following parathyroid hormone activation of the stem cell niche. The expansion of stem cells by PTH was superphysiologic in the absence of OPN. Therefore, OPN is a restricting element of the stem cell niche, limiting the number of stem cells produced by niche activation. Extracellular matrix components such as OPN may serve as modulable, regulatory participants in the stem cell niche.

scholarly journals Bone Marrow Adipocytes: The Enigmatic Components of the Hematopoietic Stem Cell Niche

2019 ◽  
Vol 8 (5) ◽  
pp. 707 ◽  
Author(s):  
Vincent Cuminetti ◽  
Lorena Arranz
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Stem Cell Niche ◽  
Functional Responses ◽  
Hematopoietic Stem ◽  
Bone Marrow Adipocytes ◽  
Hematopoietic Stem Cell Niche ◽  
Cell Niche

Bone marrow adipocytes (BMA) exert pleiotropic roles beyond mere lipid storage and filling of bone marrow (BM) empty spaces, and we are only now beginning to understand their regulatory traits and versatility. BMA arise from the differentiation of BM mesenchymal stromal cells, but they seem to be a heterogeneous population with distinct metabolisms, lipid compositions, secretory properties and functional responses, depending on their location in the BM. BMA also show remarkable differences among species and between genders, they progressively replace the hematopoietic BM throughout aging, and play roles in a range of pathological conditions such as obesity, diabetes and anorexia. They are a crucial component of the BM microenvironment that regulates hematopoiesis, through mechanisms largely unknown. Previously considered as negative regulators of hematopoietic stem cell function, recent data demonstrate their positive support for hematopoietic stem cells depending on the experimental approach. Here, we further discuss current knowledge on the role of BMA in hematological malignancies. Early hints suggest that BMA may provide a suitable metabolic niche for the malignant growth of leukemic stem cells, and protect them from chemotherapy. Future in vivo functional work and improved isolation methods will enable determining the true essence of this elusive BM hematopoietic stem cell niche component, and confirm their roles in a range of diseases. This promising field may open new pathways for efficient therapeutic strategies to restore hematopoiesis, targeting BMA.

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