The Use of Adipose Derived Cells for Skin Nerve Regeneration – Short Review of Experimental Research
Agnes S Klar1,2*, Jakub Zimoch1,2 and Thomas Biedermann1,2
1University Children’s Hospital Zurich, Tissue Biology Research Unit, August Forel Strasse 7, 8008 Zurich, Switzerland
2Children’s Research Center, University Children’s Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland
- *Corresponding Author:
- Thomas Biedermann
University Children’s Hospital Zurich
Tissue Biology Research Unit
August Forel Strasse 7
8008 Zurich, Switzerland
Tel: +41 44 6348920
E-mail: [email protected]
Received date: January 21, 2017; Accepted date: February 07, 2017; Published date: February 10, 2017
Citation: Klar AS, Zimoch J, Biedermann T (2017) The Use of Adipose Derived Cells for Skin Nerve Regeneration – Short Review of Experimental Research. J Tissue Sci Eng 8:191. doi:10.4172/2157-7552.1000191
Copyright: ©2017 Klar AS, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Burns and other severe skin injuries alter cutaneous perception of pain, temperature, and touch. During skin wound healing, peripheral nerve regeneration can occur from nerve endings of the wound bed, however, a functional recovery after an injury is often not sufficient due to scar formation or impaired wound healing.
Adipose-derived stem cells; Cell-based therapies; Skin
wound healing; Stromal vascular fraction; Nerve regeneration;
Burns and other severe skin injuries alter cutaneous perception of
pain, temperature, and touch. During skin wound healing, peripheral
nerve regeneration can occur from nerve endings of the wound bed,
however, a functional recovery after an injury is often not sufficient
due to scar formation or impaired wound healing.
Experimental studies have demonstrated that Schwann cells derived
from nerves can enhance peripheral nerve regeneration [1-4].
Unfortunately, the clinical use of Schwann cells is problematic, as they
have only limited in vitro expansion capacity. Therefore, alternatives
are needed to promote nerve regeneration.
Recently, adult stromal vascular fraction (SVF) and adipose-derived stem cells (ASCs) emerged as promising cell sources for tissueengineering
and regenerative medicine applications due to their
relative abundance and accessibility.
In this short review, we present possible applications of SVF and
ASCs in the field of skin nerve regeneration as several reports have
demonstrated that both SVF [5,6] and ASCs contribute to peripheral
nerve regeneration [7,8].
The SVF is a heterogeneous population of various cell types
including among many others adipose stromal and hematopoietic stem
cells, progenitor cells, endothelial cells, lymphocytes, pericytes, as wells
as monocytes and macrophages [9,10]. The culture of SVF cells on
tissue culture plastic allows the expansion of a subset of adherent,
multipotent stromal/stem cells. These cells are termed as adiposederived
stem cells (ASCs) and can be maintained in culture.
For nerve repair and regeneration, freshly isolated SVF or cultured
ASCs are utilized. Mohammadi et al. demonstrated in implanted fibrin
conduits containing SVF a rapid axon recovery, and an increased
density and thickness of myelinated fibers . Other strategies have
demonstrated the effectiveness of ASCs seeded for instance in silicon conduits and applied in vivo to support functional nerve regeneration
Further, another strategy is based on the differentiation of ASCs
into Schwann-like cells before using them for nerve repair. Kingham et
al. differentiated rat ASCs into Schwann-like cells employing several
growth factors mimicking Schwann cell developmental stimuli such as
FGF (fibroblast growth factor), PDGF (plateled-derived growth
factor), and glial growth factor 2 . Differentiated rat [4,15,16] and
also human [17,18] Schwann-like cells expressed in vitro myelin
proteins, glial markers, and induced neurite sprouting. Further, coculturing
of ASCs with Schwann cells resulted also in differentiation of
ASCs into Schwann-like cells [19-21].
In vivo studies have revealed that ASCs-differentiated Schwann-like
cells promoted nerve repair and regeneration when delivered in
distinct scaffolds, such as fibrin and silicon [22-28]. Tomita et al.
demonstrated improved cutaneous nerve regeneration in skin flaps
after treatment with ASCs-differentiated Schwann-like cells . Skin
innervation was accelerated by pivotal neurotrophic factors and
neurotransmitters such as nerve growth factor (NGF) and brain
derived neurotrophic factor (BDNF) supporting regrowth of cutaneous
axons from the wound bed.
However, there is still no clear evidence whether differentiated
Schwann-like cells actively participate in the formation of new myelin
sheets or if they only support already present “professional” Schwann
cells by releasing various growth factors stimulating nerve
To summarize, all aforementioned investigations using human
freshly isolated SVF, cultured ASCs or ASCs-differentiated Schwannlike
cells have been performed in vitro or in experimental in vivo
studies, but no clinical translation was performed so far. However,
further preclinical in vivo studies are needed to confirm the safety and
effectiveness of human SVF or ASCs prior to their use in future clinical
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