|
- 积分
- 299
- 威望
- 299
- 包包
- 1702
|
Mol Ther. 2011 Mar;19(3):584-93. Epub 2010 Nov 30./ c$ R" I, d( ^1 U( z0 l8 _; c- W
' C& i) O. X/ U7 O, K
Generation of HIV-1 Resistant and Functional Macrophages From Hematopoietic Stem Cell-derived Induced Pluripotent Stem Cells.
# z- _# S$ R$ M7 P# fKambal A, Mitchell G, Cary W, Gruenloh W, Jung Y, Kalomoiris S, Nacey C, McGee J, Lindsey M, Fury B, Bauer G, Nolta JA, Anderson JS.
: \* q$ v6 j7 A( [2 ?4 H) M2 m5 C
Stem Cell Program, Department of Internal Medicine, University of California, Davis, Sacramento, California, USA.1 O& K5 t8 W: m* P
) d3 X r' x4 k% S
Abstract8 ]8 D: `0 F5 w! ?' l0 P
Induced pluripotent stem cells (iPSCs) have radically advanced the field of regenerative medicine by making possible the production of patient-specific pluripotent stem cells from adult individuals. By developing iPSCs to treat HIV, there is the potential for generating a continuous supply of therapeutic cells for transplantation into HIV-infected patients. In this study, we have used human hematopoietic stem cells (HSCs) to generate anti-HIV gene expressing iPSCs for HIV gene therapy. HSCs were dedifferentiated into continuously growing iPSC lines with four reprogramming factors and a combination anti-HIV lentiviral vector containing a CCR5 short hairpin RNA (shRNA) and a human/rhesus chimeric TRIM5α gene. Upon directed differentiation of the anti-HIV iPSCs toward the hematopoietic lineage, a robust quantity of colony-forming CD133(+) HSCs were obtained. These cells were further differentiated into functional end-stage macrophages which displayed a normal phenotypic profile. Upon viral challenge, the anti-HIV iPSC-derived macrophages exhibited strong protection from HIV-1 infection. Here, we demonstrate the ability of iPSCs to develop into HIV-1 resistant immune cells and highlight the potential use of iPSCs for HIV gene and cellular therapies.% Y+ N! u9 ~, n+ b' E L: Q
6 I0 l, ?4 [7 O4 S+ J: B1 s; L8 F e
|
-
总评分: 威望 + 2
包包 + 5
查看全部评分
|
发表于 2011-3-24 15:13
