Pleiotrophin gene therapy for peripheral ischemia: evaluation of full-length and truncated gene variants.
Pleiotrophin gene therapy for peripheral ischemia: evaluation of full-length and truncated gene variants.
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外周缺血的多效性基因治疗：全长和截短基因变异的评估。
DOI：
10.1371/journal.pone.0061413
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Springer ML
中科院分区：
文献类型：
--
作者：
Fang Q;Mok PY;Thomas AE;Haddad DJ;Saini SA;Clifford BT;Kapasi NK;Danforth OM;Usui M;Ye W;Luu E;Sharma R;Bartel MJ;Pathmanabhan JA;Ang AA;Sievers RE;Lee RJ;Springer ML
Pleiotroin(PTN)是一种促血管生成和有限促肿瘤活性的生长因子。我们使用全长基因和缺失与肿瘤发生有关的结构域的截短基因变体，评估了PTN用于安全的血管生成基因治疗的可能性。转导小鼠成肌细胞表达全长或截短的PTN(PTN或T-PTN)和LacZ报告基因，并注射到小鼠四肢肌肉和心肌中。在培养的成肌细胞中，PTN通过高尔基体表达和分泌，但T-PTN不能正常分泌。然而，在表达任何一种形式的PTN的细胞中没有观察到不受控制的生长的证据。PTN基因转移到心肌和非缺血骨骼肌，没有导致可检测到的血管或功能变化。在植入后14天的缺血后肢，肌肉注射表达PTN的成肌细胞导致皮肤灌注量和肌肉小动脉密度显著增加。我们得出的结论是：(1)全长PTN基因可以在没有肿瘤形成的情况下传递到肌肉中；(2)由于分泌效率低下，截短的PTN基因可能难以用于基因治疗；(3)PTN基因传递导致了小鼠急性缺血后肢模型的功能优势。
Pleiotrophin (PTN) is a growth factor with both pro-angiogenic and limited pro-tumorigenic activity. We evaluated the potential for PTN to be used for safe angiogenic gene therapy using the full length gene and a truncated gene variant lacking the domain implicated in tumorigenesis. Mouse myoblasts were transduced to express full length or truncated PTN (PTN or T-PTN), along with a LacZ reporter gene, and injected into mouse limb muscle and myocardium. In cultured myoblasts, PTN was expressed and secreted via the Golgi apparatus, but T-PTN was not properly secreted. Nonetheless, no evidence of uncontrolled growth was observed in cells expressing either form of PTN. PTN gene delivery to myocardium, and non-ischemic skeletal muscle, did not result in a detectable change in vascularity or function. In ischemic hindlimb at 14 days post-implantation, intramuscular injection with PTN-expressing myoblasts led to a significant increase in skin perfusion and muscle arteriole density. We conclude that (1) delivery of the full length PTN gene to muscle can be accomplished without tumorigenesis, (2) the truncated PTN gene may be difficult to use in a gene therapy context due to inefficient secretion, (3) PTN gene delivery leads to functional benefit in the mouse acute ischemic hindlimb model.
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影响因子：
5.6
作者：
Heiss, Christian;Wong, Maelene L.;Springer, Matthew L.
通讯作者：
Springer, Matthew L.
影响因子：
15.9
作者：
Ozawa, CR;Banfi, A;Blau, HM
通讯作者：
Blau, HM
DOI：
10.1073/pnas.90.18.8392
发表时间：
1993-09-15
影响因子：
11.1
作者：
PEAR, WS;NOLAN, GP;BALTIMORE, D
通讯作者：
BALTIMORE, D
影响因子：
24
作者：
Henry, Timothy D.;Grines, Cindy L.;Engler, Robert L.
通讯作者：
Engler, Robert L.
DOI：
10.1126/science.1191035
发表时间：
2010-08-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gilbert PM;Havenstrite KL;Magnusson KE;Sacco A;Leonardi NA;Kraft P;Nguyen NK;Thrun S;Lutolf MP;Blau HM
通讯作者：
Blau HM