Insulin-like growth factor-I enhances lymphoid and myeloid reconstitution after allogeneic bone marrow transplantation Journal Article
| Authors: | Alpdogan, O.; Muriglan, S. J.; Kappel, B. J.; Doubrovina, E.; Schmaltz, C.; Schiro, R.; Eng, J. M.; Greenberg, A. S.; Willis, L. M.; Rotolo, J. A.; O'Reilly, R. J.; van den Brink, M. R. M. |
| Article Title: | Insulin-like growth factor-I enhances lymphoid and myeloid reconstitution after allogeneic bone marrow transplantation |
| Abstract: | Background. Prolonged immunodeficiency after allogeneic bone marrow transplantation (allo BMT) results in significant morbidity and mortality from infection. Previous studies in murine syngeneic BMT models have demonstrated that posttransplantation insulin-like growth factor (IGF)-I administration could enhance immune reconstitution. Methods. To analyze the effects of IGF-I on immune reconstitution and graft-versus-host disease (GVHD) after allo BMT, we used murine models for MHC-matched and -mismatched allo BMT. Young (3-month-old) recipient mice received 4 mg/kg per day of human IGF-I from days 14 to 28 by continuous subcutaneous administration. Results. IGF-I administration resulted in increased thymic precursor populations (triple negative-2 and triple negative-3) as determined on day 28 but had no effect on overall thymic cellularity. In the periphery, the numbers of donor-derived splenic CD3+ T cells were increased and these cells had an improved proliferative response to mitogen stimulation. IGF-I treatment also significantly increased the numbers of pro-, pre-, and mature B cells and myeloid cell populations in the spleens of allo BMT recipients on day 28. The administration of IGF-I in combination with interleukin 7 had a remarkable additive effect on B-cell, but not on T-cell, lymphopoiesis. Finally, we tested the effects of IGF-I administration on the development of GVHD in three different MHC-matched and -mismatched models and found no changes in GVHD morbidity and mortality. Conclusion. IGF-I administration can enhance lymphoid and myeloid reconstitution after allo BMT without aggravating GVHD. |
| Keywords: | controlled study; transplantation, homologous; drug potentiation; nonhuman; cd3 antigen; cell proliferation; t lymphocyte; t-lymphocytes; mouse; animals; mice; animal tissue; bone marrow cells; immune system; interleukin 7; animal experiment; animal model; allogenic bone marrow transplantation; cell differentiation; drug effect; mice, inbred c57bl; b lymphocyte; mice, inbred strains; lymphocyte activation; thymus; graft versus host reaction; bone marrow cell; somatomedin c; immune deficiency; major histocompatibility complex; bone marrow transplantation; graft vs host disease; lymphopoiesis; insulin-like growth factor i; infusions, parenteral; spleen cell; mice, inbred c3h; transplantation, isogeneic; lymphoid cell; granulocytes; humans; female; priority journal; article |
| Journal Title: | Transplantation |
| Volume: | 75 |
| Issue: | 12 |
| ISSN: | 0041-1337 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2003-06-27 |
| Start Page: | 1977 |
| End Page: | 1983 |
| Language: | English |
| PUBMED: | 12829897 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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