Dunnett Stephen B
Department of Biosciences, The Brain Repair Group, Cardiff University, Cardiff, Wales, UK.
Handb Clin Neurol. 2013;110:43-59. doi: 10.1016/B978-0-444-52901-5.00004-6.
Transplants of cells and tissues to the central nervous system of adult mammals can, under appropriate conditions, survive, integrate, and function. In particular, the grafted cells can sustain functional recovery in animal models of a range of neurodegenerative conditions including genetic and idiopathic neurodegenerative diseases of adulthood and aging, ischemic stroke, and brain and spinal cord trauma. In a restricted subset of such conditions, cell transplantation has progressed to application in humans in early-stage clinical trials. At the present stage of play, there is clear evidence of clinical efficacy of fetal cell transplants in Parkinson disease (notwithstanding a range of technical difficulties still to be fully resolved), and preliminary claims of promising outcomes in several other severe neurodegenerative conditions, including Huntington disease and stroke. Moreover, the experimental literature is increasingly suggesting that the experience and training of the graft recipient materially affects the functional outcome. For example, environmental enrichment, behavioral activity, and specific training can enhance the recovery process to maximize functional recovery. There are even circumstances where the grafted cells have been demonstrated to restore the neural substrate for new learning. Consequently, it is not sufficient to replace lost cells anatomically; rather, for the grafts to be effective, they need to be integrated functionally into the host circuitry, and the host animal requires training and rehabilitation to maximize function of the reconstructed graft-host circuitry. Such observations require reconsideration of the design of the next generation of clinical trials and subsequent service delivery, to include physiotherapists, cognitive therapists, and rehabilitation experts as core members of the transplant team, along with the neurologists and neurosurgeons that have conventionally led the field.
在适当条件下，将细胞和组织移植到成年哺乳动物的中枢神经系统中，这些移植的细胞能够存活、整合并发挥功能。特别是，在一系列神经退行性疾病的动物模型中，包括成年期和老年期的遗传性和特发性神经退行性疾病、缺血性中风以及脑和脊髓创伤，移植的细胞能够促进功能恢复。在这类疾病的一个有限子集中，细胞移植已在早期临床试验中推进到人体应用阶段。在目前阶段，有明确证据表明胎儿细胞移植在帕金森病中具有临床疗效（尽管仍有一系列技术难题有待完全解决），并且在包括亨廷顿病和中风在内的其他几种严重神经退行性疾病中也有初步的积极疗效报告。此外，实验文献越来越多地表明，移植受体的经验和训练会对功能结果产生重大影响。例如，丰富的环境、行为活动和特定训练可以增强恢复过程，以最大限度地实现功能恢复。甚至在某些情况下，已证明移植的细胞能够恢复新学习的神经基础。因此，仅仅在解剖学上替代丢失的细胞是不够的；相反，为了使移植有效，它们需要在功能上整合到宿主神经回路中，并且宿主动物需要训练和康复以最大限度地发挥重建的移植 - 宿主神经回路的功能。这些观察结果需要重新考虑下一代临床试验的设计以及后续的服务提供，将物理治疗师、认知治疗师和康复专家纳入移植团队的核心成员，与传统上引领该领域的神经科医生和神经外科医生一起。
