Abstract
Peripheral nerves have the intrinsic capacity of self-regeneration after traumatic injury but the extent of the regeneration is often very poor. Increasing evidence demonstrates that mesenchymal stem/stromal cells (MSCs) may play an important role in tissue regeneration through the secretion of soluble trophic factors that enhance and assist in repair by paracrine activation of surrounding cells. In the present study, the therapeutic value of a population of umbilical cord tissue-derived MSCs, obtained by a proprietary method (UCX(®)), was evaluated on end-to-end rat sciatic nerve repair. Furthermore, in order to promote both, end-to-end nerve fiber contacts and MSC cell-cell interaction, as well as reduce the flush away effect of the cells after administration, a commercially available haemostatic sealant, Floseal(®), was used as vehicle. Both, functional and morphologic recoveries were evaluated along the healing period using extensor postural thrust (EPT), withdrawal reflex latency (WRL), ankle kinematics analysis, and either histological analysis or stereology, in the hyper-acute, acute and chronic phases of healing. The histological analysis of the hyper-acute and acute phase studies revealed that in the group treated with UCX(®) alone the Wallerian degeneration was improved for the subsequent process of regeneration, the fiber organization was higher, and the extent of fibrosis was lower. The chronic phase experimental groups revealed that treatment with UCX(®) induced an increased number of regenerated fibers and thickening of the myelin sheet. Kinematics analysis showed that the ankle joint angle determined for untreated animals was significantly different from any of the treated groups at the instant of initial contact (IC). At opposite toe off (OT) and heel rise (HR), differences were found between untreated animals and the groups treated with either uCx(®) alone or UCX(®) administered with Floseal(®). Overall, the UCX(®) application presented positive effects in functional and morphologic recovery, in both the acute and chronic phases of the regeneration process. Kinematics analysis has revealed positive synergistic effects brought by Floseal(®) as vehicle for MSCs.
Highlights
A full understanding of nerve regeneration, namely complete functional achievement and organ re-innervation after nerve injury, still remains a main goal for regenerative medicine
In order to assay for UCX® capacity for trilineage differentiation, UCX® expanded to P5 were incubated with specific differentiation media as described in the methods section
Together these results show that UCX® meet the minimum definition criteria of Mesenchymal stem cells (MSCs), according to the ISCT. 3.2
Summary
A full understanding of nerve regeneration, namely complete functional achievement and organ re-innervation after nerve injury, still remains a main goal for regenerative medicine. Peripheral nerve injury has a high regenerative potential, but functional recovery rarely occurs after total nerve transection. In the peripheral nervous system, nerves can spontaneously regenerate without any treatment if nerve continuity is maintained (axonotmesis), whereas more severe type of injuries must be surgically treated by direct end-to-end surgical reconnection of the damaged nerve ends [1,2,3]. Mesenchymal stem cells (MSCs) have become one of the most interesting agents for regenerative medicine. Scientific and clinical evidence have demonstrated that MSCs have the ability to migrate to specific sites of injury or of tissue regeneration where they modulate the immune and the inflammatory responses and mobilize intrinsic cell reservoirs through a series of distinct paracrine mechanisms [7]. MSCs are capable of differentiating into tri-lineage mesenchyme cell types, such as adipocytes, Received 27 Sep 2013; accepted 23 Jan 2014; published online: 30 April 2014
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