Sca-1(+) hematopoietic cell-based gene therapy with a modified FGF-2 increased endosteal/trabecular bone formation in mice.

Sca-1(+) hematopoietic cell-based gene therapy with a modified FGF-2 increased endosteal/trabecular bone formation in mice. Research Abstract Details 

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Sca-1(+) hematopoietic cell-based gene therapy with a modified FGF-2 increased endosteal/trabecular bone formation in mice. Abstract Text:

Susan L Hall,Kin-Hing William Lau,Shin-Tai Chen,Jon E Wergedal,Apurva Srivastava,Henry Klamut,Matilda H-C Sheng,Daila S Gridley,Subburaman Mohan,David J Baylink,Susan L Hall,Kin-Hing William Lau,Shin-Tai Chen,Jon E Wergedal,Apurva Srivastava,Henry Klamut,Matilda H-C Sheng,Daila S Gridley,Subburaman Mohan,David J Baylink,

This study assessed the feasibility of using an ex vivo stem cell antigen-1-positive (Sca-1(+)) cell-based systemic fibroblast growth factor-2 (FGF-2) gene therapy to promote endosteal bone formation. Sca-1(+) cells were used because of their ability to home to, and engraft into, the bone marrow cavity. The human FGF-2 gene was modified to increase protein secretion and stability by adding the bone morphogenic protein (BMP)-2/4 hybrid signal sequence and by mutating two key cysteines. Retro-orbital injection of Sca-1(+) cells transduced with a Moloney leukemia virus (MLV)-based vector expressing the modified FGF-2 gene into sub-lethally irradiated W(41)/W(41) recipient mice resulted in long-term engraftment, more than 100-fold elevation in serum FGF-2 level, increased serum bone-formation markers, and massive endosteal bone formation. In recipient mice showing very high serum FGF-2 levels (>2,000 pg/ml), this enhanced endosteal bone formation was so robust that the marrow space was filled with bony tissues and insufficient calcium was available for the mineralization of all the newly formed bone, which led to secondary hyperparathyroidism and osteomalacia. These adverse effects appeared to be dose related. In conclusion, this study provided compelling test-of-principle evidence for the feasibility of using an Sca-1(+) cell-based ex vivo systemic FGF-2 gene therapy strategy to promote endosteal bone formation.

Sca-1(+) hematopoietic cell-based gene therapy with a modified FGF-2 increased endosteal/trabecular bone formation in mice. Publishing Authors By Initials

SL Hall,KH Lau,ST Chen,JE Wergedal,A Srivastava,H Klamut,MH Sheng,DS Gridley,S Mohan,DJ Baylink,SL Hall,KH Lau,ST Chen,JE Wergedal,A Srivastava,H Klamut,MH Sheng,DS Gridley,S Mohan,DJ Baylink,

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Sca-1(+) hematopoietic cell-based gene therapy with a modified FGF-2 increased endosteal/trabecular bone formation in mice. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Molecular therapy : the journal of the American So

VOLUME: 15

Page Numbers: 1881-9

Journal Abbreviation: Mol. Ther.

ISSN: 1525-0016

DAY: 17

MONTH: 07

YEAR: 2007

Sca-1(+) hematopoietic cell-based gene therapy with a modified FGF-2 increased endosteal/trabecular bone formation in mice. Information

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LANGUAGE: eng

NlmUniqueID: 100890581

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Grant and Affiliation Information for Sca-1(+) hematopoietic cell-based gene therapy with a modified FGF-2 increased endosteal/trabecular bone formation in mice.

AFFILIATION: Musculoskeletal Disease Center, Jerry L. Pettis Memorial V.A. Medical Center, Loma Linda, California 92357, USA.

Country: United States

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MEDLINETA: Mol Ther

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