Wolfson Centre for Age-Related Diseases, King's College London, UK.
Br Med Bull. 2011;98:127-42. doi: 10.1093/bmb/ldr013. Epub 2011 May 17.
A large number of different cells including embryonic and adult stem cells have been transplanted into animal models of spinal cord injury, and in many cases these procedures have resulted in modest sensorimotor benefits. In October 2010 the world's first clinical trial using human embryonic stem cells began, using stem cells converted into oligodendrocyte precursor cells.
In this review we examine some of the publically available preclinical evidence that some of these cell types improve outcome in animal models of spinal cord injury. Much evidence is not available for public scrutiny, however, being private commercial property of various stem cell companies.
Transplantation of many different types of stem and progenitor cell enhances spontaneous recovery of function when transplanted acutely after spinal cord injury in animal models. AREAS OF DISAGREEMENT: The common mechanism(s) whereby the generic procedure of cellular transplantation enhances recovery of function are not well understood, although a range of possibilities are usually cited (including preservation of tissue, remyelination, axon sprouting, glial cell replacement). Only in exceptional cases has it been shown that functional recovery depends causally on the survival and differentiation of the transplanted cells. There is no agreement about the optimal cell type for transplantation: candidate stem cells have not yet been compared with each other or with other cell types (e.g. autologous Schwann cells) in a single study.
Transplantation of cells into animals with a long lifespan is important to determine whether or not tumours will eventually form. It will also be important to determine whether long-term survival of cells is required for functional recovery, and if so, how many are optimal.
大量不同的细胞,包括胚胎和成体干细胞,已被移植到脊髓损伤的动物模型中,在许多情况下,这些方法都导致了适度的感觉运动益处。2010 年 10 月,世界上第一个使用人类胚胎干细胞的临床试验开始,使用转化为少突胶质前体细胞的干细胞。
在这篇综述中,我们检查了一些公开的临床前证据,这些证据表明,这些细胞类型中的一些可以改善动物脊髓损伤模型的结果。然而,许多证据无法供公众审查,因为它们是各种干细胞公司的私人商业财产。
在动物模型中,急性移植后,许多不同类型的干细胞和祖细胞移植可增强功能的自发恢复。
细胞移植增强功能恢复的通用程序的常见机制尚不清楚,尽管通常会引用一系列可能性(包括组织保存、髓鞘形成、轴突发芽、胶质细胞替代)。只有在极少数情况下,已经表明功能恢复取决于移植细胞的存活和分化。关于最佳移植细胞类型尚未达成共识:候选干细胞尚未在单个研究中彼此或与其他细胞类型(例如自体雪旺细胞)进行比较。
将细胞移植到寿命长的动物中很重要,以确定是否最终会形成肿瘤。还需要确定细胞的长期存活是否是功能恢复所必需的,如果是,多少是最佳的。