Increased plasma levels of stromal-derived factor-1 (SDF-1/CXCL12) enhance human thrombopoiesis and mobilize human colony-forming cells (CFC) in NOD/SCID mice Journal Article
| Authors: | Perez, L. E.; Alpdogan, O.; Shieh, J.H.; Wong, D.; Merzouk, A.; Salari, H.; O'Reilly, R. J.; van den Brink, M. R. M.; Moore, M. A. S. |
| Article Title: | Increased plasma levels of stromal-derived factor-1 (SDF-1/CXCL12) enhance human thrombopoiesis and mobilize human colony-forming cells (CFC) in NOD/SCID mice |
| Abstract: | Objective. Stromal-derived factor-1 (SDF-1/CXCL12) is chemotactic for lympho/hematopoietic stem cells. We have previously shown that increasing peripheral blood (PB) levels of SDF-1 with adenovectors expressing human SDF-1 complementary DNA (ad-SDF-1) leads to hematopoietic stem cell mobilization as well as migration of megakaryocytes and thrombocytosis in mice. Herein, we studied the in vivo effects of ad-SDF-1 and of an analogue peptide of SDF-1 (CTCE-0214) on human hematopoiesis in a xenotransplant model. Materials and Methods. Sublethally irradiated (300 cGY) NOD/SCID mice transplanted with human cord blood mononuclear cells (CB MNC) were injected with ad-SDF-1 (10 9 plaque forming units, IV, x1) or CTCE-0214 (10 mg/kg/dose, IV q 24 hours x7). Effects on megakaryocytopoiesis (CD41+ cells and platelets) as well as stem cell mobilization were monitored. Results. CB MNC in NOD/SCID mice are able to differentiate into CD41+ cells and platelets, peaking at week 9 at a mean of 3.7 × 103/μL. IV injection of ad-SDF-1 increased human CD41+ cells by day 4 in PB and was followed by an increase in human platelet production by day 5, with return to baseline by day 30. Human colony-forming cells (CFC) were mobilized from bone marrow to spleen (by day 6-13) and to PB (by day 13). Human CD34 + and CD33+ cells were mobilized by this treatment as well. A novel SDF-1 peptide agonist (CTCE-0214) also mobilized human CFC and enhanced human thrombopoiesis. Conclusion. SDF-1 and its analogue may be of clinical value in stimulating platelet recovery after chemo/radiation treatment as well as in stem cell mobilization. © 2004 International Society for Experimental Hematology. Published by Elsevier Inc. |
| Keywords: | controlled study; nonhuman; animal cell; mouse; animals; mice; cd34 antigen; thrombocyte; spleen; in vivo study; cell differentiation; mice, scid; drug evaluation, preclinical; peptide; genetic vectors; transduction, genetic; fetal blood; mononuclear cell; recombinant fusion proteins; thrombosis; stem cell mobilization; transplantation, heterologous; umbilical cord blood; hematopoiesis; mice, inbred nod; hematopoietic stem cell mobilization; cd33 antigen; adenoviridae; blood level; megakaryocytes; blood platelets; thrombopoietin; stromal cell derived factor 1; colony forming cell; fibrinogen receptor; chemokines, cxc; megakaryopoiesis; humans; human; priority journal; article; radiation chimera |
| Journal Title: | Experimental Hematology |
| Volume: | 32 |
| Issue: | 3 |
| ISSN: | 0301-472X |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2004-03-01 |
| Start Page: | 300 |
| End Page: | 307 |
| Language: | English |
| DOI: | 10.1016/j.exphem.2003.12.005 |
| PROVIDER: | scopus |
| PUBMED: | 15003316 |
| DOI/URL: | |
| Notes: | Exp. Hematol. -- Cited By (since 1996):40 -- Export Date: 16 June 2014 -- CODEN: EXHEB -- Source: Scopus |
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