Increasing Human Neural Stem Cell Transplantation Dose Alters Oligodendroglial and Neuronal Differentiation after Spinal Cord Injury.
Increasing Human Neural Stem Cell Transplantation Dose Alters Oligodendroglial and Neuronal Differentiation after Spinal Cord Injury.
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DOI：
10.1016/j.stemcr.2017.04.009
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发表时间：
2017-06-06
影响因子：
5.9
通讯作者：
Anderson AJ
中科院分区：
文献类型：
--
作者：
Piltti KM;Funes GM;Avakian SN;Salibian AA;Huang KI;Carta K;Kamei N;Flanagan LA;Monuki ES;Uchida N;Cummings BJ;Anderson AJ
Multipotent human central nervous system-derived neural stem cells transplanted at doses ranging from 10,000 (low) to 500,000 (very high) cells differentiated predominantly into the oligodendroglial lineage. However, while the number of engrafted cells increased linearly in relationship to increasing dose, the proportion of oligodendrocytic cells declined. Increasing dose resulted in a plateau of engraftment, enhanced neuronal differentiation, and increased distal migration caudal to the transplantation sites. Dose had no effect on terminal sensory recovery or open-field locomotor scores. However, total human cell number and decreased oligodendroglial proportion were correlated with hindlimb girdle coupling errors. Conversely, greater oligodendroglial proportion was correlated with increased Ab step pattern, decreased swing speed, and increased paw intensity, consistent with improved recovery. These data suggest that transplant dose, and/or target niche parameters can regulate donor cell engraftment, differentiation/maturation, and lineage-specific migration profiles. SCI niche may have a limited capacity for donor cell engraftment Dose alters the donor cell lineage-specific fate and migration profile Increasing hindlimb girdle couplings errors may be due to increased total cell numbers Greater proportion of oligodendroglial cells improves locomotor recovery In this article, Piltti and colleagues investigate the effect of human neural stem cell transplant dose on engraftment, death, differentiation, lineage-specific migration, and recovery of sensory and locomotor function after spinal cord injury. The data indicate that the effect of dose should be considered in the development of clinical cell transplantation protocols.
