Improved Stem Cell-Derived Motoneuron Survival, Migration, Sprouting, and Innervation with Enhanced Expression of Polysialic Acid
| Autor: | Damali Moyo Lee Yaw, Urs Rutishauser, Abderrahman El Maarouf |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Cell engineering
Neurite Cell Survival Biomedical Engineering lcsh:Medicine Mice Transgenic Biology urologic and male genital diseases Mice Cell Movement Neurites Animals Embryonic Stem Cells Motor Neurons Transplantation Polysialic acid lcsh:R Cell Biology Sciatic Nerve Embryonic stem cell Axons Sialyltransferases Cell biology Sialic Acids Stem cell Stem Cell Transplantation Sprouting |
| Zdroj: | Cell Transplantation, Vol 24 (2015) |
| ISSN: | 1555-3892 0963-6897 |
| Popis: | Motoneurons (MNs) derived from mouse embryonic stem cells (ESCs) begin to express low levels of polysialic acid (PSA) at the time when they acquire an ability to migrate and extend neurites. PSA is known to promote cell migration and process outgrowth/guidance in the developing nervous system. To test if experimentally enhanced expression of PSA would augment these cellular events, the PSA-synthesizing polysialyltransferase was introduced into ESCs. In culture, the resulting higher PSA expression specifically increased neurite outgrowth and cell migration from differentiated embryoid bodies. In addition, the MN population obtained after sorting for HB9::GFP expression showed enhanced survival as well as extensive neurite outgrowth. Following transplantation of ESC-derived MNs into an adult sciatic nerve devoid of endogenous axons, the PSA augmentation increased the numbers of axons growing toward the denervated muscles. Migration of some transplanted cells inside the nerve toward muscle was also enhanced. Moreover, higher PSA expression selectively affected target innervation. It produced greater numbers of neuromuscular junctions in a predominantly fast twitch muscle and had no effect in a slow twitch muscle. These findings suggest that engineering of PSA expression in ESC could serve as an enhancement for MN cell therapy. |
| Databáze: | OpenAIRE |
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