Encapsulated human primary myoblasts deliver functional hFIX in hemophilic mice.

Encapsulated human primary myoblasts deliver functional hFIX in hemophilic mice. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Encapsulated human primary myoblasts deliver functional hFIX in hemophilic mice. Abstract Text:

Jianping Wen,Nong Xu,Anna Li,Jacqueline Bourgeois,Frederick A Ofosu,Gonzalo Hortelano,Jianping Wen,Nong Xu,Anna Li,Jacqueline Bourgeois,Frederick A Ofosu,Gonzalo Hortelano,

BACKGROUND: Hemophilia B is a bleeding disorder caused by defective factor IX (FIX), currently treated by regular infusions of plasma-derived or recombinant FIX. We propose a gene therapy strategy based on the implantation of cells secreting FIX enclosed in alginate microcapsules as a highly desirable alternative treatment. We have reported sustained delivery of human factor IX (hFIX) in immunocompetent mice implanted with encapsulated primary mouse myoblasts engineered to secrete hFIX. As a step towards the treatment of human patients, in this study we report the implantation of encapsulated human primary myoblasts secreting hFIX in hemophilia B mice. METHODS: Human primary myoblasts were transfected with plasmids pKL4M-hFIX, pLNM-betaIXL, pMFG-hFIX, and transduced with retrovirus MFG-hFIX. Two human primary myoblast clones secreting approximately 1 microg hFIX/10(6) cells/day were enclosed in biocompatible alginate microcapsules and implanted intraperitoneally into SCID and hemophilic mice. RESULTS: Circulating hFIX (peak of approximately 120 ng/ml) was detected in hemophilia B mice on day 1 after implantation. Human FIX delivery was transient, however, becoming undetectable on day 14. Concurrently, anti-hFIX antibodies were detected. At the same time, activated partial thromboplastin time (APTT) was reduced from 94 s before treatment to 78-80 s. Tail bleeding time decreased from 15 min to 1.5-7 min after treatment, some mice being normalised. These findings indicate that the delivered hFIX is biologically active. Similarly treated NOD/SCID mice had circulating hFIX levels of 170 ng/ml on day 1 that remained detectable for 1 month, albeit at low levels. Cell viability of microcapsules retrieved on day 60 was below 5%. CONCLUSIONS: Our findings indicate that encapsulated human primary myoblasts secrete functional hFIX. Furthermore, implantation of encapsulated human primary myoblasts can partially correct the phenotype of hemophilia B mice, supporting the feasibility of this gene therapy approach for hemophilia B. However, the long-term viability of the encapsulated human myoblasts must first be improved. Copyright (c) 2007 John Wiley & Sons, Ltd.

Encapsulated human primary myoblasts deliver functional hFIX in hemophilic mice. Publishing Authors By Initials

J Wen,N Xu,A Li,J Bourgeois,FA Ofosu,G Hortelano,J Wen,N Xu,A Li,J Bourgeois,FA Ofosu,G Hortelano,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Encapsulated human primary myoblasts deliver functional hFIX in hemophilic mice. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: The journal of gene medicine

VOLUME: 9

Page Numbers: 1002-10

Journal Abbreviation:

ISSN: 1099-498X

DAY: 29

MONTH: Nov

YEAR: 2007

Encapsulated human primary myoblasts deliver functional hFIX in hemophilic mice. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9815764

Encapsulated human primary myoblasts deliver functional hFIX in hemophilic mice. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Encapsulated human primary myoblasts deliver functional hFIX in hemophilic mice. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Encapsulated human primary myoblasts deliver functional hFIX in hemophilic mice.

AFFILIATION: Research & Development, Canadian Blood Services, McMaster University, Hamilton, Ontario, L8N 3Z5 Canada.

Country: England

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: J Gene Med

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Encapsulated human primary myoblasts deliver functional hFIX in hemophilic mice Related Publications

• Differential sensitivity to apoptosis among the cells that contribute to the atherosclerotic disease.
• Encapsulated human primary myoblasts deliver functional hFIX in hemophilic mice.