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自体成肌细胞心肌内移植:组织处理能否优化?

Intramyocardial transplantation of autologous myoblasts: can tissue processing be optimized?

作者信息

Pouzet B, Vilquin J T, Hagège A A, Scorsin M, Messas E, Fiszman M, Schwartz K, Menasché P

机构信息

Service de Chirurgie Cardiovasculaire, Groupe Hospitalier Bichat-Claude Bernard, Paris, France.

出版信息

Circulation. 2000 Nov 7;102(19 Suppl 3):III210-5. doi: 10.1161/01.cir.102.suppl_3.iii-210.

DOI:10.1161/01.cir.102.suppl_3.iii-210
PMID:11082389
Abstract

BACKGROUND

Autologous skeletal myoblast (SM) transplantation improves function of infarcted myocardium, but pretransplantation cultures remain a complex process. This study assessed whether it could be optimized by muscle preconditioning with the local anesthetic bupivacaine or even bypassed with the use of the so-called mince technique.

METHODS AND RESULTS

Muscle preconditioning consisted of intramuscular injections of the tibialis anterior of rats, 2 days before harvest. After 7 days of culture, the number of available myoblasts was significantly increased compared with nonconditioned controls (1 683 147 versus 85 300, P:=0.0013). The mince technique was then assessed. A myocardial infarction was created in 66 rats by coronary artery ligation. One week later, rats were reoperated on and intramyocardially injected with culture medium alone (controls, n=23), autologous cultured SM (3.5 x 10(6), n=21), or autologous muscle minced into a fine slurry, which was immediately transplanted (n=22). All muscles had been preconditioned. Left ventricular function was assessed by 2D echocardiography. Whereas end-diastolic volumes expanded over time in all groups, left ventricular ejection fraction (%, mean+/-SEM) was increased only in the cultured SM-transplanted group at 1 (P:=0. 0006) and 2 months (P:=0.0008) versus baseline (37.52+/-1.92 and 40. 92+/-2.17 versus 30.34+/-1.74), with a significant additional benefit between 1 and 2 months (P:=0.0069).

CONCLUSIONS

Cell culture remains mandatory for SM transplantation to be successful but, in a clinical perspective, this process can be made more expeditious by preharvest muscle conditioning with bupivacaine, which greatly enhances the baseline cell yield.

摘要

背景

自体骨骼肌成肌细胞(SM)移植可改善梗死心肌的功能,但移植前的培养仍是一个复杂的过程。本研究评估了是否可以通过用局部麻醉药布比卡因进行肌肉预处理来优化该过程,甚至是否可以通过使用所谓的切碎技术来绕过该过程。

方法与结果

肌肉预处理包括在收获前2天对大鼠胫前肌进行肌肉内注射。培养7天后,与未预处理的对照组相比,可用成肌细胞的数量显著增加(1683147对85300,P = 0.0013)。然后评估切碎技术。通过冠状动脉结扎在66只大鼠中制造心肌梗死。一周后,大鼠再次手术,心肌内仅注射培养基(对照组,n = 23)、自体培养的SM(3.5×10⁶,n = 21)或切碎成细浆并立即移植的自体肌肉(n = 22)。所有肌肉均经过预处理。通过二维超声心动图评估左心室功能。虽然所有组的舒张末期容积随时间增加,但仅在培养的SM移植组中,左心室射血分数(%,平均值±标准误)在1个月(P = 0.0006)和2个月(P = 0.0008)时相对于基线增加(37.52±1.92和40.92±2.17对30.34±1.74),在1至2个月之间有显著的额外益处(P = 0.0069)。

结论

细胞培养对于SM移植成功仍然是必不可少的,但从临床角度来看,通过用布比卡因进行收获前肌肉预处理可以使这个过程更快,这大大提高了基线细胞产量。

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