Bone marrow stromal cells as a genetic platformfor systemic delivery of therapeutic proteins in vivo : human factor IX model
dc.contributor.author | Krebsbach, Paul H. | en_US |
dc.contributor.author | Zhang, Kezhong | en_US |
dc.contributor.author | Malik, Ajay K. | en_US |
dc.contributor.author | Kurachi, Kotoku | en_US |
dc.date.accessioned | 2006-04-19T14:18:00Z | |
dc.date.available | 2006-04-19T14:18:00Z | |
dc.date.issued | 2003-01 | en_US |
dc.identifier.citation | Krebsbach, Paul H.; Zhang, Kezhong; Malik, Ajay K.; Kurachi, Kotoku (2003)."Bone marrow stromal cells as a genetic platformfor systemic delivery of therapeutic proteins in vivo : human factor IX model." The Journal of Gene Medicine 5(1): 11-17. <http://hdl.handle.net/2027.42/35232> | en_US |
dc.identifier.issn | 1099-498X | en_US |
dc.identifier.issn | 1521-2254 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/35232 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=12516047&dopt=citation | en_US |
dc.description.abstract | Background Hemophilia B is an X-linked bleeding disorder that results from a deficiency in functional coagulation factor IX (hFIX). In patients lacking FIX, the intrinsic coagulation pathway is disrupted leading to a lifelong, debilitating and sometimes fatal disease. Methods We have developed an ex vivo gene therapy system using genetically modified bone marrow stromal cells (BMSCs) as a platform for sustained delivery of therapeutic proteins into the general circulation. This model exploits the ability of BMSCs to form localized ectopic ossicles when transplanted in vivo . BMSCs were transduced with MFG-hFIX, a retroviral construct directing the expression of hFIX. The biological activity of hFIX expressed by these cells was assessed in vitro and in vivo . Results Transduced cells produced biologically active hFIX in vitro with a specific activity of 90% and expressed hFIX at levels of ∼497 ng/10 6 cells/24 h and 322 ng/10 6 cells/24 h for human and porcine cells, respectively. The secretion of hFIX was confirmed by Western blot analysis of the conditioned medium using a hFIX-specific antibody. Transduced BMSCs (8 × 10 6 cells per animal) were transplanted within scaffolds into subcutaneous sites in immunocompromised mice. At 1 week post-implantation, serum samples contained hFIX at levels greater than 25 ng/ml. Circulating levels of hFIX gradually decreased to 11.5 ng/ml at 1 month post-implantation and declined to a stable level at 6.1 ng/ml at 4 months. Conclusions These findings demonstrate that genetically modified BMSCs can continuously secrete biologically active hFIX from self-contained ectopic ossicles in vivo , and thus represent a novel delivery system for releasing therapeutic proteins into the circulation. Copyright © 2002 John Wiley & Sons, Ltd. | en_US |
dc.format.extent | 185890 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | John Wiley & Sons, Ltd. | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Genetics | en_US |
dc.title | Bone marrow stromal cells as a genetic platformfor systemic delivery of therapeutic proteins in vivo : human factor IX model | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Biological Chemistry | en_US |
dc.subject.hlbsecondlevel | Genetics | en_US |
dc.subject.hlbsecondlevel | Molecular, Cellular and Developmental Biology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | University of Michigan School of Dentistry, Department of Oral Medicine, Pathology, and Oncology, Ann Arbor, Michigan, USA ; University of Michigan School of Dentistry, Dept. of Oral Medicine, Pathology, and Oncology, 1011 N. University Ave., Ann Arbor, MI 48109-1078, USA. | en_US |
dc.contributor.affiliationum | University of Michigan School of Medicine, Department of Human Genetics, Ann Arbor, Michigan, USA | en_US |
dc.contributor.affiliationum | University of Michigan School of Medicine, Department of Human Genetics, Ann Arbor, Michigan, USA | en_US |
dc.contributor.affiliationum | University of Michigan School of Medicine, Department of Human Genetics, Ann Arbor, Michigan, USA | en_US |
dc.identifier.pmid | 12516047 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/35232/1/292_ftp.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1002/jgm.292 | en_US |
dc.identifier.source | The Journal of Gene Medicine | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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