Macrophage inflammatory protein 1 alpha, interleukin 3 and diffusible marrow stromal factors maintain human hematopoietic stem cells for at least eight weeks in vitro

doi:10.1084/jem.179.2.643

This Article

	Full Text (PDF)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Verfaillie, C. M.
	Articles by Li, W. N.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Verfaillie, C. M.
	Articles by Li, W. N.


Social Bookmarking

	What's this?

ARTICLES

Macrophage inflammatory protein 1 alpha, interleukin 3 and diffusible marrow stromal factors maintain human hematopoietic stem cells for at least eight weeks in vitro

CM Verfaillie, PM Catanzarro and WN Li
Department of Medicine, University of Minnesota, Minneapolis 55454.

Factors that induce proliferation of the human hematopoietic stem cell are ill-defined. Primitive hematopoietic progenitors can be maintained and differentiate in stroma-dependent, long-term bone marrow cultures (LTBMC), originally described by Dexter et al. (Dexter, T. M., L. H. Coutinho, E. Spooncer, C. M. Heyworth, C. P. Daniel, R. Schiro, J. Chang, and T. D. Allen. 1990. Molecular Control of Haemopoiesis). However, 70-80% of primitive progenitors capable of reinitiating secondary stromal cultures (LTBMC-initiating cells [IC]) are lost over a period of 5 wk in such cultures. We have recently described a novel "stroma-noncontact" culture system, in which hematopoietic progenitors are separated from the stromal layer by a 0.4-micron microporous filter membrane. Primitive progenitors in such cultures can not only differentiate into committed progenitors, but are also maintained to a greater extent than in "Dexter" cultures. However, still only 50% of the originally seeded LTBMC-IC are recovered at week 5. Since maintenance of primitive progenitors may depend not only on growth- promoting factors but also on factors that inhibit differentiation and/or proliferation, we evaluated the effect of macrophage inflammatory protein 1 alpha (MIP-1 alpha) or "stem cell inhibitor" in combination with the growth-inducing factor interleukin 3 (IL-3) on the recovery of LTBMC-IC from stroma-noncontact cultures. We demonstrate that addition of MIP-1 alpha alone to stroma-noncontact cultures does not change the number of LTBMC-IC present after 8 wk, indicating that this factor may not directly inhibit or stimulate proliferation of primitive progenitors. Addition of the growth stimulatory cytokine, IL- 3, alone results in exhaustion of LTBMC-IC after 8 wk of culture, possibly as a result of their terminal differentiation. However, LTBMC- IC can be maintained for at least 8 wk when grown in stroma-noncontact cultures supplemented with both MIP-1 alpha plus IL-3. This effect depends on soluble (ill-defined) stromal factors, and results from a direct interaction of these cytokines with the progenitor population or its progeny, but not the stroma.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Stringer, S. E., Nelson, M. S., Gupta, P. (2003). Identification of an MIP-1alpha -binding heparan sulfate oligosaccharide that supports long-term in vitro maintenance of human LTC-ICs. Blood 101: 2243-2245 [Abstract] [Full Text]
Forssmann, U., Magert, H.-J., Adermann, K., Escher, S. E., Forssmann, W.-G. (2001). Hemofiltrate CC chemokines with unique biochemical properties: HCC-1/CCL14a and HCC-2/CCL15. J. Leukoc. Biol. 70: 357-366 [Abstract] [Full Text]
Kimura, T., Wang, J., Minamiguchi, H., Fujiki, H., Harada, S., Okuda, K., Kaneko, H., Yokota, S., Yasukawa, K., Abe, T., Sonoda, Y. (2000). Signal through gp130 Activated by Soluble Interleukin (IL)-6 Receptor (R) and IL-6 or IL-6R/IL-6 Fusion Protein Enhances Ex Vivo Expansion of Human Peripheral Blood-Derived Hematopoietic Progenitors. Stem Cells 18: 444-452 [Abstract] [Full Text]
Peled, A., Kollet, O., Ponomaryov, T., Petit, I., Franitza, S., Grabovsky, V., Slav, M. M., Nagler, A., Lider, O., Alon, R., Zipori, D., Lapidot, T. (2000). The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34+ cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice. Blood 95: 3289-3296 [Abstract] [Full Text]
Gupta, P., Oegema, T. R. Jr, Brazil, J. J., Dudek, A. Z., Slungaard, A., Verfaillie, C. M. (2000). Human LTC-IC can be maintained for at least 5 weeks in vitro when interleukin-3 and a single chemokine are combined with O-sulfated heparan sulfates: requirement for optimal binding interactions of heparan sulfate with early-acting cytokines and matrix proteins. Blood 95: 147-155 [Abstract] [Full Text]
Czaplewski, L. G., McKeating, J., Craven, C. J., Higgins, L. D., Appay, V., Brown, A., Dudgeon, T., Howard, L. A., Meyers, T., Owen, J., Palan, S. R., Tan, P., Wilson, G., Woods, N. R., Heyworth, C. M., Lord, B. I., Brotherton, D., Christison, R., Craig, S., Cribbes, S., Edwards, R. M., Evans, S. J., Gilbert, R., Morgan, P., Randle, E., Schofield, N., Varley, P. G., Fisher, J., Waltho, J. P., Hunter, M. G. (1999). Identification of Amino Acid Residues Critical for Aggregation of Human CC Chemokines Macrophage Inflammatory Protein (MIP)-1alpha , MIP-1beta , and RANTES. CHARACTERIZATION OF ACTIVE DISAGGREGATED CHEMOKINE VARIANTS. J. Biol. Chem. 274: 16077-16084 [Abstract] [Full Text]
Nicholls, S. E., Lucas, G., Graham, G. J., Russell, N. H., Mottram, R., Whetton, A. D., Buckle, A.-M. (1999). Macrophage-Inflammatory Protein-1{alpha} Receptor Expression on Normal and Chronic Myeloid Leukemia CD34+ Cells. J. Immunol. 162: 6191-6199 [Abstract] [Full Text]
Gupta, P., Oegema, T. R. Jr, Brazil, J. J., Dudek, A. Z., Slungaard, A., Verfaillie, C. M. (1998). Structurally Specific Heparan Sulfates Support Primitive Human Hematopoiesis by Formation of a Multimolecular Stem Cell Niche. Blood 92: 4641-4651 [Abstract] [Full Text]
de Wynter, E.A., Durig, J., Cross, M.A., Heyworth, C.M., Testa, N.G. (1998). Differential Response of CD34+ Cells Isolated from Cord Blood and Bone Marrow to MIP-1{alpha} and the Expression of MIP-1{alpha} Receptors on These Immature Cells. Stem Cells 16: 349-356 [Abstract] [Full Text]
Wang, J.-F., Liu, Z.-Y., Groopman, J. E. (1998). The alpha -Chemokine Receptor CXCR4 Is Expressed on the Megakaryocytic Lineage From Progenitor to Platelets and Modulates Migration and Adhesion. Blood 92: 756-764 [Abstract] [Full Text]
Miller, J. S., McCullar, V., Verfaillie, C. M. (1998). Ex Vivo Culture of CD34+/Lin-/DR- Cells in Stroma-Derived Soluble Factors, Interleukin-3, and Macrophage Inflammatory Protein-1alpha Maintains Not Only Myeloid But Also Lymphoid Progenitors in a Novel Switch Culture Assay. Blood 91: 4516-4522 [Abstract] [Full Text]
Peled, A., Gonzalo, J. A., Lloyd, C., Gutierrez-Ramos, J.-C. (1998). The Chemotactic Cytokine Eotaxin Acts as a Granulocyte-Macrophage Colony-Stimulating Factor During Lung Inflammation. Blood 91: 1909-1916 [Abstract] [Full Text]
Dao, M. A., Shah, A. J., Crooks, G. M., Nolta, J. A. (1998). Engraftment and Retroviral Marking of CD34+ and CD34+CD38- Human Hematopoietic Progenitors Assessed in Immune-Deficient Mice. Blood 91: 1243-1255 [Abstract] [Full Text]
Breems, D. A., Blokland, E. A.W., Siebel, K. E., Mayen, A. E.M., Engels, L. J.A., Ploemacher, R. E. (1998). Stroma-Contact Prevents Loss of Hematopoietic Stem Cell Quality During Ex Vivo Expansion of CD34+ Mobilized Peripheral Blood Stem Cells. Blood 91: 111-117 [Abstract] [Full Text]
Rollins, B. J. (1997). Chemokines. Blood 90: 909-928 [Full Text]
Gahn, B., Schafer, C., Neef, J., Troff, C., Feuring-Buske, M., Hiddemann, W., Wormann, B. (1997). Detection of Trisomy 12�and Rb-Deletion in CD34+ Cells of Patients With B-Cell Chronic Lymphocytic Leukemia. Blood 89: 4275-4281 [Abstract] [Full Text]
Prosper, F., Vanoverbeke, K., Stroncek, D., Verfaillie, C. M. (1997). Primitive Long-Term Culture Initiating Cells (LTC-ICs) in Granulocyte Colony-Stimulating Factor Mobilized Peripheral Blood Progenitor Cells Have Similar Potential for Ex Vivo Expansion as Primitive LTC-ICs in Steady State Bone Marrow. Blood 89: 3991-3997 [Abstract] [Full Text]
Bertolini, F., Battaglia, M., Pedrazzoli, P., Antonio Da Prada, G., Lanza, A., Soligo, D., Caneva, L., Sarina, B., Murphy, S., Thomas, T., Robustelli della Cuna, G. (1997). Megakaryocytic Progenitors Can Be Generated Ex Vivo and Safely Administered to Autologous Peripheral Blood Progenitor Cell Transplant Recipients. Blood 89: 2679-2688 [Abstract] [Full Text]
Takakura, N., Kodama, H., Nishikawa, S., Nishikawa, S.-I. (1996). Preferential Proliferation of Murine Colony-forming Units in Culture in a Chemically Defined Condition with a Macrophage Colony-stimulating Factor-negative Stromal Cell Clone. J. Exp. Med. 184: 2301-2310 [Abstract] [Full Text]