Promoting Nerve Regeneration in a Neurotmesis Rat Model Using Poly(DL-lactide-ε-caprolactone) Membranes and Mesenchymal Stem Cells from the Wharton’s Jelly : In Vitro and In Vivo Analysis

• Published in: BioMed research international Vol. 2014; no. 2014; pp. 1 - 17
• Main Authors: Fregnan, Federica, Varejão, A. S. P., Santos, J. Domingos, Bartolo, P. J., Geuna, Stefano, Luís, A. L., Mauricio, Ana C., Pereira, T., Amado, Sandra, Armada-da-Silva, Paulo A. S., Caseiro, A. R., Gärtner, A., Amorim, Irina, Almeida, A.
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Puplishing Corporation 01.01.2014; Hindawi Publishing Corporation; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Animals; Biomechanical Phenomena - drug effects; Biomedical research; Cell Differentiation - drug effects; Colleges & universities; Disease Models, Animal; Gene expression; Humans; Immunohistochemistry; Injuries; Karyotyping; Membranes; Membranes, Artificial; Mesenchymal Stem Cell Transplantation; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Nerve Regeneration - drug effects; Nervous system; Neuroglia - cytology; Neuroglia - drug effects; Neurological research; Peripheral Nerve Injuries - pathology; Peripheral Nerve Injuries - physiopathology; Peripheral Nerve Injuries - therapy; Polyesters - pharmacology; Rats; Reaction Time; Reflex - drug effects; Regeneration; Reproducibility of Results; Sciatic Nerve - drug effects; Sciatic Nerve - pathology; Sciatic Nerve - physiopathology; Stem cells; Wharton Jelly - cytology
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2014/302659

In peripheral nerves MSCs can modulate Wallerian degeneration and the overall regenerative response by acting through paracrine mechanisms directly on regenerating axons or upon the nerve-supporting Schwann cells. In the present study, the effect of human MSCs from Wharton’s jelly (HMSCs), differentiated into neuroglial-like cells associated to poly (DL-lactide-ε-caprolactone) membrane, on nerve regeneration, was evaluated in the neurotmesis injury rat sciatic nerve model. Results in vitro showed successful differentiation of HMSCs into neuroglial-like cells, characterized by expression of specific neuroglial markers confirmed by immunocytochemistry and by RT-PCR and qPCR targeting specific genes expressed. In vivo testing evaluated during the healing period of 20 weeks, showed no evident positive effect of HMSCs or neuroglial-like cell enrichment at the sciatic nerve repair site on most of the functional and nerve morphometric predictors of nerve regeneration although the nociception function was almost normal. EPT on the other hand, recovered significantly better after HMSCs enriched membrane employment, to values of residual functional impairment compared to other treated groups. When the neurotmesis injury can be surgically reconstructed with an end-to-end suture or by grafting, the addition of a PLC membrane associated with HMSCs seems to bring significant advantage, especially concerning the motor function recovery.