Association of Stromal Cell–Derived Factor-1-3′A Polymorphism to Higher Mobilization of Hematopoietic Stem Cells CD34+ in Tunisian Population

Abstract The establishment of the HSC pool in vertebrates depends not only on the formation and the propagation of these stem cells but also on their proper trafficking among the defined hematopoietic organs. However, the physiologic mechanisms that regulate HSC mobilization remain elusive. Through analysis of the zebrafish cmyb mutant cmybhkz3, we show that the suppression of cMyb function abrogates larval and adult hematopoiesis, with concomitant accumulation of hematopoietic stem/progenitor cells (HSPCs) in their birthplace, the ventral wall of the dorsal aorta (VDA). Cell tracking and time-lapse recording reveal that the accumulation of HSPCs in cmybhkz3 mutants is caused by the impairment of HSPC egression from the VDA. Further analysis demonstrates that the HSPC migratory defects in cmybhkz3 mutants are at least partly because of adversely elevated levels of chemokine stromal cell-derived factor 1a (Sdf1a). Our study reveals that cMyb plays a hitherto unidentified role in dictating physiologic HSPC migration by modulating Sdf1a signaling.

Download Full-text

Native associations of early hematopoietic stem cells and stromal cells isolated in bone marrow cell aggregates

Blood ◽

10.1182/blood.v83.2.361.bloodjournal832361 ◽

1994 ◽

Vol 83 (2) ◽

pp. 361-369 ◽

Cited By ~ 1

Author(s):

PE Funk ◽

PW Kincade ◽

PL Witte

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Stem Cell ◽

Hematopoietic Stem Cells ◽

Stromal Cells ◽

Stromal Cell ◽

Hematopoietic Cells ◽

Hematopoietic Stem ◽

Factor C

In suspensions of murine bone marrow, many stromal cells are tightly entwined with hematopoietic cells. These cellular aggregations appear to exist normally within the marrow. Previous studies showed that lymphocytes and stem cells adhered to stromal cells via vascular cell adhesion molecule 1 (VCAM1). Injection of anti-VCAM1 antibody into mice disrupts the aggregates, showing the importance of VCAM1 in the adhesion between stromal cells and hematopoietic cells in vivo. Early hematopoietic stem cells were shown to be enriched in aggregates by using a limiting-dilution culture assay. Myeloid progenitors responsive to WEHI-3CM in combination with stem cell factor (c-kit ligand) and B220- B-cell progenitors responsive to insulin-like growth factor-1 in combination with interleukin-7 are not enriched. We propose a scheme of stromal cell-hematopoietic cell interactions based on the cell types selectively retained within the aggregates. The existence of these aggregates as native elements of bone marrow organization presents a novel means to study in vivo stem cell-stromal cell interaction.

Download Full-text

A secreted and LIF-mediated stromal cell–derived activity that promotes ex vivo expansion of human hematopoietic stem cells

Blood ◽

10.1182/blood.v95.6.1957 ◽

2000 ◽

Vol 95 (6) ◽

pp. 1957-1966 ◽

Cited By ~ 40

Author(s):

Chu-Chih Shih ◽

Mickey C.-T. Hu ◽

Jun Hu ◽

Yehua Weng ◽

Paul J. Yazaki ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Hematopoietic Stem Cells ◽

Stromal Cells ◽

Cell Expansion ◽

Culture System ◽

Stromal Cell ◽

Ex Vivo ◽

Hematopoietic Stem ◽

Stem Cell Expansion

Abstract The development of culture systems that facilitate ex vivo maintenance and expansion of transplantable hematopoietic stem cells (HSCs) is vital to stem cell research. Establishment of such culture systems will have significant impact on ex vivo manipulation and expansion of transplantable stem cells in clinical applications such as gene therapy, tumor cell purging, and stem cell transplantation. We have recently developed a stromal-based culture system that facilitates ex vivo expansion of transplantable human HSCs. In this stromal-based culture system, 2 major contributors to the ex vivo stem cell expansion are the addition of leukemia inhibitory factor (LIF) and the AC6.21 stromal cells. Because the action of LIF is indirect and mediated by stromal cells, we hypothesized that LIF binds to the LIF receptor on AC6.21 stromal cells, leading to up-regulated production of stem cell expansion promoting factor (SCEPF) and/or down-regulated production of stem cell expansion inhibitory factor (SCEIF). Here we demonstrate a secreted SCEPF activity in the conditioned media of LIF-treated AC6.21 stromal cell cultures (SCM-LIF). The magnitude of ex vivo stem cell expansion depends on the concentration of the secreted SCEPF activity in the SCM-LIF. Furthermore, we have ruled out the contribution of 6 known early-acting cytokines, including interleukin-3, interleukin-6, granulocyte macrophage colony-stimulating factor, stem cell factor, flt3 ligand, and thrombopoietin, to this SCEPF activity. Although further studies are required to characterize this secreted SCEPF activity and to determine whether this secreted SCEPF activity is mediated by a single factor or by multiple growth factors, our results demonstrate that stromal cells are not required for this secreted SCEPF activity to facilitate ex vivo stem cell expansion.

Download Full-text

Bone marrow stromal cells induce myeloid and lymphoid development of the sorted hematopoietic stem cells in vitro

Blood ◽

10.1182/blood.v86.7.2590.2590 ◽

1995 ◽

Vol 86 (7) ◽

pp. 2590-2597 ◽

Cited By ~ 17

Author(s):

R Okuyama ◽

M Koguma ◽

N Yanai ◽

M Obinata

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Hematopoietic Stem Cells ◽

Stromal Cell ◽

Simian Virus 40 ◽

Simian Virus ◽

T Antigen ◽

Stem Cell Population ◽

Hematopoietic Stem

Abstract Regulation of development of hematopoietic stem cells was examined by culturing Lin- c-Kit+ Sca1+ stem cells sorted from bone marrow (BM) cells by fluorescence-activated cell sorting on a layer of TBR59, a BM stromal cell line established from simian virus 40 T-antigen gene transgenic mice. The sorted stem cells did not show self-renewal, but two waves (at 7 and 13 days) of a cobblestone formation were induced by the stromal cell layer. The cobblestones were formed by finite cell division (eight divisions on average) of sorted Lin-c-Kit+ Sca1+ stem cells, and divided cells were still immature. The c-Kithigh stem cell population was induced to form the first wave of cobblestone formation committed to myeloid lineage, whereas c-Kitlow population was induced to form the second wave of this formation committed to lymphoid lineage. Both cobblestone formations require c-Kit function, but very late activation antigen-4-vascular cell adhesion molecule-1 interaction plays different parts in the two lineages.

Download Full-text