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Titolo:
Human mesenchymal stem cells maintain transgene expression during expansion and differentiation
Autore:
Lee, K; Majumdar, MK; Buyaner, D; Hendricks, JK; Pittenger, MF; Mosca, JD;
Indirizzi:
Osiris Therapeut Inc, Baltimore, MD 21231 USA Osiris Therapeut Inc Baltimore MD USA 21231 Inc, Baltimore, MD 21231 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 6, volume: 3, anno: 2001,
pagine: 857 - 866
SICI:
1525-0016(200106)3:6<857:HMSCMT>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
MEDIATED GENE-TRANSFER; PERIPHERAL-BLOOD LYMPHOCYTES; MARROW STROMAL CELLS; RETROVIRAL VECTOR; PROGENITOR CELLS; IN-VIVO; EPIDERMAL-KERATINOCYTES; MONOCLONAL-ANTIBODIES; THERAPY; TRANSDUCTION;
Keywords:
mesenchymal stem cell; retroviral transduction; differentiation; transgene expression; NOD/SCID mice; interleukin-3; green fluorescent protein;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
74
Recensione:
Indirizzi per estratti:
Indirizzo: Mosca, JD Adv Biotechnol Inc, Rivers Pk 2,9108 Guilford Rd, Columbia, MD 21046 USA Adv Biotechnol Inc Rivers Pk 2,9108 Guilford Rd Columbia MD USA 21046
Citazione:
K. Lee et al., "Human mesenchymal stem cells maintain transgene expression during expansion and differentiation", MOL THER, 3(6), 2001, pp. 857-866

Abstract

Human adult bone marrow contains both hematopoietic stem cells that generate cells of all hematopoietic lineages and human mesenchymal stem cells (hMSCs), which support hematopoiesis and contribute to the regeneration of multiple connective tissues. The goal of the current study was to demonstrate that transduced hMSCs maintain transgene expression after stem cell differentiation in vitro and in vivo. We have introduced genes into cultured hMSCsby retroviral vector transfer and demonstrated long-term in vitro and in vivo expression of human interleukin 3 (hIL-3) and green fluorescent protein(GFP). Protocols were developed to achieve transduction efficiencies of 80-90% in these stem cells. In vitro expression of hIL-3 averaged 350 ng/10(6)cells/24 h over 17 passages (>6 months) and GFP expression was stable overthe same time period. Transduced hMSCs were able to differentiate into osteogenic, adipogenic, and chondrogenic lineages and maintained transgene expression after differentiation. Parallel studies were performed in vivo using NOD/SCID mice. Human MSCs expressing hIL-3 were cultured on several matrices and then delivered by subcutaneous, intravenous, and intraperitoneal routes. Sampling of peripheral blood demonstrated that systemic hIL-3 expression was maintained in the range of 100-800 pg/ml over a period of 3 months. These results illustrate the ability of hMSCs to express genes of therapeutic potential and demonstrate their potential clinical utility as cellular vehicles for systemic gene delivery.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 16/02/20 alle ore 21:08:36