THE FUNCTIONAL-CHARACTERISTICS OF SCHWANN-CELLS CULTURED FROM HUMAN PERIPHERAL-NERVE AFTER TRANSPLANTATION INTO A GAP WITHIN THE RAT SCIATIC-NERVE
THE FUNCTIONAL-CHARACTERISTICS OF SCHWANN-CELLS CULTURED FROM HUMAN PERIPHERAL-NERVE AFTER TRANSPLANTATION INTO A GAP WITHIN THE RAT SCIATIC-NERVE
复制标题
DOI：
10.1523/jneurosci.14-03-01309.1994
复制
发表时间：
1994-03-01
影响因子：
5.3
通讯作者：
BUNGE, RP
中科院分区：
文献类型：
--
作者：
LEVI, ADO;GUENARD, LV;BUNGE, RP
在使用人类雪旺细胞(SCs)进行移植以促进中枢和周围神经组织的再生之前，必须努力确定调节其功能表达的因素。成人来源的干细胞可以在培养中分离和纯化，但允许其完全分化的培养条件尚未确定。我们通过将这些细胞移植到免疫缺陷大鼠受损的三叉神经核中，测试了它们在体内增强轴突再生和髓鞘再生轴突的功能能力。从器官供体获取的人周围神经中分离纯化出SCs。将30%Matrigel溶液按80×10(8)个/ml的密度加入或不加入人干细胞悬液填充半透性引导通道，将通道植入裸鼠坐骨神经横断的8 mm缝隙内，连续4周。通过分离再生电缆上的神经外植体(首先将其放置在培养5d后)并对单个细胞进行灵长类特异性神经生长因子受体(PNGFr)和S100中PNGFr阳性细胞的一半染色来确定移植的人SCs的存活率，这表明再生电缆中含有大致相同数量的人和大鼠(宿主)SCs。用HNK-1抗体免疫染色证实了某些人髓鞘片段的存在，HNK-1抗体专门标记人而不是大鼠髓鞘。然而，再生电缆中的大部分髓鞘片段是由大鼠干细胞产生的。与仅含稀释液的通道相比，种植了人干细胞的通道中有髓轴突的数量和电缆的横截面积显著增加。我们的结论是，纯化培养的人干细胞移植到免疫缺陷大鼠受损的三叉神经核后，可以存活并显著促进轴突再生。一些移植的人类干细胞能够使再生的大鼠轴突髓鞘形成，但不如宿主干细胞成功。
The use of human Schwann cells (SCs) in transplantation to promote regeneration in central and peripheral neural tissues must be preceded by efforts to define the factors that regulate their functional expression. Adult-derived human SCs can be isolated and purified in culture, but the culture conditions that allow their full differentiation have not yet been defined. We tested the functional capacity of these cells to enhance axonal regeneration and myelinate regenerating axons in vivo by transplanting them into the damaged PNS of an immune-deficient rat. SCs were purified from human peripheral nerve obtained from organ donors. Semipermeable guidance channels were filled with a 30% Matrigel containing solution with or without human SCs suspended at a density of 80 x 10(8) cells/ml. Channels were implanted within an 8 mm gap of the transected sciatic nerve of nude female rats for a period of 4 weeks. Survival of the transplanted human SCs was established by dissociating nerve explants taken from the regenerated cable (after first placing them in culture for 5 d) and staining individual cells for a primate-specific NGF receptor (PNGFr) and S100 Only one-half of the S100-positive cells stained for the PNGFr, which indicated that the regenerated cable contained an approximately equal number of human and rat (host) SCs. The presence of some human myelin segments was confirmed by immune staining with an HNK-1 antibody that specifically labels human but not rat myelin. The majority of the myelin segments in the regenerated cable, however, were produced by the rat SCs. The number of myelinated axons and the cross-sectional area of the cable were significantly greater in channels seeded with human SCs when compared to channels containing the diluted Matrigel solution alone. We conclude that purified cultured human SCs can survive and substantially enhance axonal regeneration when transplanted into the injured PNS of an immune-deficient rat. Some of the transplanted human SCs are capable of myelinating regenerating rat axons but are less successful than the host SCs.