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no differences in terms of regeneration between numbers CELL TRANSPLANTATION
and diameters of the channels were observed. [18]
In addition to providing a physical path for the regenerative Cell‑based therapy is considered a valid approach to
process, microchannels also act as “axonal signal amplifiers” stimulate and enhance the regeneration of the injured
when applied in nerve stimulating‑recording devices. The nerve, overcoming the delayed recruitment and response
electrical resistance of the intracellular medium is increased of endogenous SC at the injury site, and therefore
by the constricted environment, and the recorded signal reducing their progressive atrophy in vivo. SC have
of the extracellular potential is therefore amplified been either injected at the injury site or preseeded in
[36,37]
when specific electrodes are embedded in the structure, the nerve conduit, with high rates of successful
[19]
according to Fitzgerald et al., Microelectrodes arrays are axon regeneration and myelination. In addition, various
in fact commonly used to record neural activity during the growth factors expression in SC can be induced as
regeneration process at the injury site. New technological needed for the specific purpose. Prior studies have
frontiers have allowed researchers to fabricate stretchable presented successful transfections of SC with either
fibroblast growth factor (FGF) or NGF, both
[38]
[39]
electrodes to better conform and deform along the tubular stimulating nerve repair in an injury rat model. Recently,
nerve conduit, responding more anatomically to the SCs were transplanted ex vivo before implantation in
physical stress which conduits undergo in vivo and reducing order to investigate the impact of brain‑derived nerve
the inflammatory response. [16,20]
factor (BDNF), ciliary neurotrophic factor (CNTF), and
neurotrophin 3 (NT‑3) on nerve regeneration and
INFLUENCE OF EXTRACELLULAR recovery. The result was a significant improvement of
MATRIX MOLECULES AND FILLERS axon outgrowth and myelination, with cells remaining
[40]
viable for up to 8 weeks in vivo. However, the harvest
Peripheral nerves have the potential to regenerate after of autologous SC involves a significantly debilitating
injury, as opposed to the central nervous system. This biopsy from the patient. In addition, SC adhesion and
is mainly attributed to the presence of SC basement proliferation are considerably slower when compared
membranes rich in ECM components, such as laminin (LM) to cells cultured in vitro (requiring for instance the
and fibronectin (FN), which promote axonal regeneration precoating of each culture substrate), resulting in long
in the peripheral nervous system. The ECM milieu of the culture time in order to achieve a suitable number for
regenerating nerve is not simply a passive scaffold for therapeutic uses.
regrowth, as its molecules can synergistically signal with
growth factors and growth cone molecules to influence Stem cells have become very attractive in tissue
[21]
regrowth. LM, fibrin, FN and collagen are the main ECM engineering and regenerative medicine due to their
proteins used as coatings for peripheral nerve repair. ECM ability to self‑renew and differentiate into most cell
[41]
[22]
molecules such as LM, FN [23,24] and collagen have been phenotypes. Mesenchymal SCs (MSCs) are derived
[25]
shown to enhance axonal regeneration when incorporated from bone marrow stromal progenitors and have been
into nerve guidance channels. [26] demonstrated to be able to trans‑differentiate into
several cell lineages, including osteoblasts, chondrocytes,
Alternatively, FN‑ and LM‑derived peptide moieties, such endothelial cells, myocytes, neurons, and glial cells.
as RGD (Arg‑Gly‑Asp), [27,28] IKVAV (Ile‑Lys‑Val‑Ala‑Val), [29,30] In particular, when MSC are differentiated into SC‑like
[31]
and YIGSR (Tyr‑Ile‑Gly‑Ser‑Arg), have been recognized to cells, they are able to express the characteristic glial
trigger specific interactions between neural cells and the markers and enhance peripheral nerve regeneration
accordingly modified substrate. in vivo by improving myelination of axons and increasing
regeneration distances. [42]
Different from coatings, ECM proteins have been used for
the formation of gels or matrices as intraluminal fillers of Undifferentiated MSC was preseeded in a chitosan
NGCs, such as fibrin gels, shown interesting results in terms conduit in an in vivo study for 6 weeks using a rat model,
of regeneration. However, this ECM protein maintains SC with successful regeneration similar to autografting.
[17]
[32]
in a nonmyelinating state and therefore, the degradation In addition, these cells were used in a monkey model
[33]
time of the gel should be optimized in order to trigger to repair a 50‑mm median nerve defect in a long‑term
axon myelination in due time during regeneration. in vivo experiment. Cells were injected directly after
[43]
implantation at the proximal stump to overcome the
Another composite hydrogel containing collagen and
hyaluronan, with or without growth factors, was used in deficit of local SC, resulting in enhanced regenerative
properties compared to the nonseeded conduits.
combination with poly(L‑lactide‑co‑caprolactone). Both Similar outcomes comparable to autografts were then
[34]
the compound muscle action potential and the muscle assessed in a dog model, bridging a 50‑mm sciatic
recovery were improved when compared to the empty nerve gap with successful muscle reinnervation. Signs
[44]
control, while no differences were observed in presence of local transdifferentiation into an SC‑like phenotype
or absence of nerve growth factor (NGF).
were observed after 8 weeks postimplantation by
For a detailed review on the effect of ECM components Oliveira et al., resulting in higher formation of
[45]
on peripheral nerve regeneration, readers are advised to myelinated and unmyelinated axons, as well as blood
consult a recent publication. [35] vessels, when compared to empty conduits.
Plast Aesthet Res || Vol 2 || Issue 4 || Jul 15, 2015 215