Grafted murine induced pluripotent stem cells prevent death of injured rat motoneurons otherwise destined to die

Pajer, Krisztián and Nemes, Csilla and Berzsenyi, Sára and Kovács, Krisztián A. and Pirity, Melinda and Nógrádi, Antal (2015) Grafted murine induced pluripotent stem cells prevent death of injured rat motoneurons otherwise destined to die. Experimental Neurology, 269. pp. 188-201. ISSN 0014-4886

[img] Text
Restricted to Registered users only

Download (5MB) | Request a copy


Human plexus injuries often include the avulsion of one or more ventral roots, resulting in debilitating conditions. In this study the effects of undifferentiated murine iPSCs on damaged motoneurons were investigated following avulsion of the lumbar 4 (L4) ventral root, an injury known to induce the death of the majority of the affected motoneurons. Avulsion and reimplantation of the L4 ventral root (AR procedure) was accompanied by the transplantation of murine iPSCs into the injured spinal cord segment in rats. Control animals underwent ventral root avulsion and reimplantation, but did not receive iPSCs. The grafted iPSCs induced an improved reinnervation of the reimplanted ventral root by the host motoneurons as compared with the controls (number of retrogradely labeled motoneurons: 503 +/- 38 [AR+iPSCs group] vs 48 +/- 6 [controls, AR group]). Morphological reinnervation resulted in a functional recovery, i.e. the grafted animals exhibited more motor units in their reinnervated hind limb muscles, which produced a greater force than that in the controls (50 +/- 2.1% vs 11.9 +/- 4.2% maximal tetanic tension [% ratio of operated/intact side]). Grafting of undifferentiated iPCSs downregulated the astroglial activation within the L4 segment. The grafted cells differentiated into neurons and astrocytes in the injured cord. The grafted iPSCs, host neurons and glia were found to produce the cytokines and neurotrophic factors MIP-1a, IL-10, GDNF and NT-4. These findings suggest that, following ventral root avulsion injury, iPSCs are able to induce motoneuron survival and regeneration through combined neurotrophic and cytokine modulatory effects.

Item Type: Article
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia
Depositing User: MTMT SWORD
Date Deposited: 10 Feb 2016 20:00
Last Modified: 10 Feb 2016 20:00

Actions (login required)

Edit Item Edit Item