Biomedical Engineering Reference
In-Depth Information
may be responsible for the good results in post-traumatic nerve regeneration promotion ob‐
served in the sciatic nerve after axonotmesis and neurotmesis [57, 91]. The substantial im‐
provement of axonal regeneration found in sciatic nerve crush enwrapped by chitosan type
III membranes and for bridging nerve gaps after neurotmesis [57, 91], suggests that this bio‐
material may not just work as a simple mechanical device but instead may induce nerve re‐
generation. The neuroregenerative properties of chitosan type III may be explained by the
effect on SCs proliferation, axon elongation and myelinization [55, 91]. Our data also
showed that PLC does not deleteriously interfere with the nerve regeneration process, as a
matter of fact, the information on the effectiveness of PLC membranes and tube-guides for
allowing nerve regeneration was already provided experimentally and with patients [82].
The MSCs from the Wharton's jelly may be a valuable source in the repair of the peripheral
nervous system with capacity to differentiate into neuroglial-like cells. The transplanted
MSCs are also able to promote local blood vessel formation and release the neurotrophic fac‐
tors brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor
(GDNF) [55]. Previous results obtained by our research group using N1E-115 cells in vitro
differentiated into neuroglial-like cells to promote regeneration of axonotmesis and neuro‐
tmesis lesions in the rat model showed that there was no significant effect in promoting ax‐
on regeneration and, when N1E-115 cells were cultured inside a PLGA scaffold used to
bridge a nerve defect, they can even exert negative effects on nerve fiber regeneration. The
presence of transplanted N1E-115 cells in nerve scaffolds competing for the local blood sup‐
ply of nutrients and oxygen and by space-occupying effect could have hindered the positive
effect of local neurotrophic factor release leading a negative outcome on nerve regeneration.
Thus, N1E-115 cells did not prove to be a suitable candidate cellular system for treatment of
nerve injury after axonotmesis and neurotmesis and their application is limited only to re‐
search purposes as a basic scientific step for the development of other cell delivery systems,
due to its neoplastic origin [57-59, 91, 93]. The MSCs isolated from the Wharton´s jelly
through PLC and chitosan type III membranes might be a potentially valuable tool to im‐
prove clinical outcome especially after trauma to sensory nerves, such as digital nerves. The
results from our experimental work [55, 56] showed that the use of either undifferentiated or
neuroglial-like differentiated MSCs enhanced the recovery of sensory and motor function of
the rat sciatic nerve. The observation that in both cell-enriched experimental groups myelin
sheath was thicker, suggest that MSCs might exert their positive effects on SCs, the key ele‐
ment in Wallerian degeneration and the following axonal regeneration [120]. In addition,
these cells represent a non-controversial source of primitive mesenchymal progenitor cells
that can be harvested after birth, cryogenically stored, thawed, and expanded for therapeu‐
tic uses, including nerve injuries like axonotmesis and neurotmesis. The time and tempera‐
ture of the transport (and the saline solution used) of the UC units from the hospital / clinic
to the laboratory is crucial for a successful outcome considering MSCs isolation and prolifer‐
ation from fresh and cryopreserved UCT. It is highly recommend that the transport from the
clinic or hospital to the laboratory should be refrigerated, and the UC units should be imme‐
diately immersed in a sterile saline solution like HBSS or DPBS.
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