Review Article
Adipose Stem Cell-Based Clinical Strategy for Neural
Regeneration: A Review of Current Opinion
Yu-hao Wang ,1,2,3 Yu-chen Guo ,1,2 Dian-ri Wang ,1,2,3 Ji-yuan Liu ,1,2
and Jian Pan 1,2,3
1State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospitalof Stomatology, Sichuan University, Chengdu 610041, China
3
National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University,
Chengdu, Sichuan Province 610041, China
2

Correspondence should be addressed to Jian Pan; jianpancn@scu.edu.cn
Received 5 September 2019; Revised 2 November 2019; Accepted 11 November 2019; Published 19 November 2019
Guest Editor: Roberto Narcisi
Copyright © 2019 Yu-hao Wang et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Nerve injury is a critical problem in the clinic. Nerve injury causes serious clinic issues including pain and dysfunctions for patients.
The disconnection between damaged neural ﬁbers and muscles will result in muscle atrophy in a few weeks if no treatment is applied.
Moreover, scientists have discovered that nerve injury can aﬀect the osteogenic diﬀerentiation of skeletal stem cells (SSCs) and thefracture repairing. In plastic surgery, muscle atrophy and bone fracture after nerve injury have plagued clinicians for many years.
How to promote neural regeneration is the core issue of research in the recent years. Without obvious eﬀects of traditional
neurosurgical treatments, research on stem cells in the past 10 years has provided a new therapeutic strategy for us to address thisproblem. Adipose stem cells (ASCs) are a kind of mesenchymal stem cells that have diﬀerentiation potential in adipose tissue. In
the recent years, ASCs have become the focus of regenerative medicine. They play a pivotal role in tissue regeneration engineering.
As a type of stem cell, ASCs are becoming popular for neuroregenerative medicine due to their advantages and characteristics. In
the various diseases of the nervous system, ASCs are gradually applied to treat the related diseases. This review article focuses on
the mechanism and clinical application of ASCs in nerve regeneration as well as the related research on ASCs over the past decades.

1. Introduction
Nerve injury is common in the clinic and leads to many othercomplications, such as muscle atrophy and abnormal bonereconstruction. The treatments of nerve injury cost USA
medical insurance $150 billion every year, and these diseases
aﬀect 20 million Americans’ lives [1]. Nerve injury occurs in
2% to 3% of citizens, and more than 50,000 peripheral nerve
injury repair operations are performed per year in the UnitedStates [2]. Therefore, nerve injury and its complications
cause huge ﬁnancial burdens for social development andaﬀect patients’ life quality. Thus, it is critical for clinicians
to solve these urgent problems.
Nerve injury results in muscle atrophy and abnormalbone reconstruction which leads motor dysfunction. In gen-eral, satellite cells, as stem cells in skeletal muscle tissue, canrepair atrophied and damaged skeletal muscles [3–7]. However, the recovery of damaged musculoskeletal tissue requires
the involvement of nerve endings. It will form scar tissues
without the involvement of nerve endings [8]. The loss ofaxonal continuity, nerve demyelination, and neuron cell
death after nerve injury can lead to the denervation of skeletal
muscle [2]. Some studies have demonstrated that muscle
atrophy will happen after denervation within 2 weeks [9].
Furthermore, the accumulation ability of skeletal stem cells(SSCs) will decrease in the mandible with inferior alveolar
nerve injury according to the Annual Clinical Congress of
the American College of Surgeons in Boston, May 2018[10]. Scientists attending the meeting have proved that nerve
injury can aﬀect the osteogenic diﬀerentiation of SSCs and2delay the procedure of bone fracture repair [10]. The mandible is the core component of the masticatory system, and any
damage to the mandible can cause masticatory muscle disorder. The recovery of damaged nerve may have a positive
impact on the bone fracture repair, and brieﬂy, it may
provide a new strategy for skeletal muscle dysfunction andbone diseases.
The orthodox treatment for nerve injury can be divided
into two major categories: surgical methods and nonsurgicalmethods. However, both surgical and nonsurgical methods
have their own limitations. For example, Robinson et al.
found that only 4 of 53 patients who underwent neurologicaldirect suture had some degree of recovery [11]. The possible
reason is that the length of nerve defect is so long that thesutured nerve has a large tension between the sutural endings. The majority of clinicians reject to use medication alone
for treatment due to the long periodicity of drug therapy. At
present, there are no eﬀective methods to treat nerve injury inthe clinic. Fortunately, the research on stem cells and tissue
engineering in the past decades may make it possible.

2. Stem Cells
Stem cells can self-renew and diﬀerentiate into multiple lineages. Currently, scientists have isolated several kinds of adultstem cells, such as bone marrow mesenchymal stem cells(BM-MSCs), skeletal stem cells (SSCs), dental pulp stem cells(DPSCs), adipose stem cells (ASCs), neural stem cells(NSCs), fetal-derived stem cells (FDSCs), human periapicalcyst-mesenchymal stem cells (hPCy-MSCs), induced pluripotent stem cells (iPSCs), skin epidermal stem cells (SESCs),
human amniotic-mesenchymal stem cells (hAMSCs), andhair follicle stem cells (HFSCs) [12–14].
Stem cells in diﬀerent tissues can expand their quantities
by symmetrical division during the growth and developmentof the human body. Meanwhile, stem cells can self-renew
and have great ability of multidirectional diﬀerentiation to
replace damaged cells by asymmetric division when someinjuries occur in diﬀerent tissues. It has been reported that
intravenous injection of MSCs can treat acute lung and kidney injuries in preclinical trials with mouse disease models[15, 16]. ASCs derive from adipose tissues with some sharedcharacteristics of all stem cells. More importantly, it ispotential for ASCs to repair damaged tissues including nervous tissues.

3. The Fate and Biological
Characteristics of ASCs
Easy obtainable methods with little damage for stem cell harvesting are the main ambition. The quantity of ASCs in adipose tissues is 100- to 500-fold compared with that of MSCs
in bone marrow tissues. There are two types of human adipose tissue: white adipose tissue and brown adipose tissue.
Subcutaneous adipose tissue in white adipose tissue is themain source of ASCs, and this kind of ASCs has a stronger
antiapoptotic ability than ASCs located in brown adipose tissue [17]. However, ASCs from brown adipose tissue moreeasily undergo skeletal myogenic diﬀerentiation in the spe-

Stem Cells International
ciﬁc microenvironment [18, 19]. The characteristics of ASCs
make them popular in the ﬁeld of regeneration.
3.1. The Obtainable Method and Multipotential Diﬀerentiationof ASCs. It is widely accepted that ASCs can be harvested
from adipose tissues and have great ability of multidirectional diﬀerentiation. With 0.075% collagenase type II digestion, ASCs can be harvested from the stromal vascular
fraction (SVF) of adipose tissues. The ingredients of SVF
include ASCs (15~30%), endothelial cells (10-20%), pericytes(3~5%), and immune cells (25~45%) [20, 21]. Due to themesodermal origin of ASCs, they can diﬀerentiate into adipogenic, osteogenic, and chondrogenic lineages induced by
selective medium in vitro [22, 23]. Among them, the neuraldiﬀerentiation of ASCs has attracted scientists’ attention
and created a new cell-based clinical strategy for neurodegenerative diseases.
3.2. Neural Diﬀerentiation. Saﬀord et al. ﬁrstly induced
ASCs to diﬀerentiate into neuronal phenotype cells which
express nestin and neuronal nuclei protein (NeuN) in
2002 [24]. The inducing and diﬀerentiation medium theyused for neural diﬀerentiation of ASCs contained valproic
acid, butyl hydroxyanisole, insulin, and hydrocortisone.
However, this chemical method is not suitable to induce differentiation in vivo due to its disability to construct the corresponding microenvironment in the body for neuralregeneration [25]. Moreover, chemical reagents in themedium can cause some extra damage to tissues, whichbrings pain to patients.
Biological induction methods are more suitable forrepairing damaged tissues in vivo. ASCs can be induced to
diﬀerentiate into neural cells if the medium contains somesoluble factors secreted from nerve tissues which include cerebellum, hippocampus, and cerebral cortex [26]. ASCs canalso secrete some neurotrophic factors in the process of neural diﬀerentiation, such as nerve growth factor (NGF), brainderived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF),
and ﬁbroblast growth factor (FGF) [27]. The current problem
lies in how to control the direction of neural diﬀerentiation.
Both neurons and glial cells can promote the remyelinationof nerve which is of great importance for neural regenerationand express the similar markers [28–30]. However, some differences can be pointed out. A higher tendency of neuronalphenotype can be recognized when ASCs are induced byolfactory ensheathing cell conditioned medium (OEC-CM)[31, 32]. Instead, ASCs are more likely to diﬀerentiate into
glial cells in Schwann cell conditioned medium (SC-CM)
with high concentration of GFAP [31, 32].
ASCs can promote axonal regeneration, myelination, andfunctional recovery [33]. ASCs upregulate the expression of
myelin protein zero, peripheral myelin protein-22, and myelin basic protein, which promotes self-regulation of ASC differentiation and reestablishes the connection between
damaged nerve and target organs [34]. Some animal models
have proved that ASCs have neuroprotection abilities andprovide trophic supports for axon regeneration in optic nerve
transection, glaucoma, and retinitis pigmentosa [35–37].

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Furthermore, ASCs were applied to the preclinical trials
for the CNS diseases, such as Alzheimer’s disease (AD)and Parkinson’s disease (PD) [38].

4. The Regulation and Mechanism in the Neural
Differentiation of ASCs
There is a complex regulatory network in the neural diﬀerentiation of ASCs. In addition to neurotrophic factors secretedby ASCs, parts of signaling pathways are also involved in thediﬀerentiation courses. Most importantly, ASCs can promote
their own neural diﬀerentiation by regulating the microenvironment. It is widely accepted that the microenvironment
regulation interacts with the neural diﬀerentiation of ASCs[39]. The neural diﬀerentiation of ASCs takes place undercomplex regulatory mechanisms and promotes neural regeneration in order to repair damaged nervous tissues.
4.1. The Neurotrophic Eﬀect. The paracrine function of stem
cells is a kind of mechanism that accelerates the process ofneural diﬀerentiation. Undiﬀerentiated ASCs can secrete
neuroprotective factors to enhance neural regeneration andreduce muscle atrophy [40, 41]. These neuroprotective factors include BDNF, GDNF, CNTF, and neurotrophin-4[41]. Furthermore, some angiogenesis and antiapoptotic factors are also secreted by ASCs, including hepatocyte growth
factor (HGF), transforming growth factor-β (TGF-β), andvascular endothelial growth factor (VEGF) [42–46]. Some
scientists believe that the inhibition of apoptosis is a crucial
step in tissue regeneration, which is decided by the concentration of antiapoptotic factors in the microenvironment[47]. Antiapoptotic factors and neurotrophic factors can promote neuron proliferation and survival [48, 49]. Anotherimportant point is that the activation and proliferation of
microglia accelerate the process of some neurodegenerative
diseases, for example, traumatic brain injury (TBI) [50–54].
Jha et al. have proved that trophic factors secreted by ASCs
can normalize microglia and slow down the development ofneurodegenerative diseases [55].
Neurotrophic factor is a sort of protein molecule necessary for the growth and survival of neurons [56]. Amongthe known neurotrophic factors, BDNF is one of the mostimportant factors in the development of the nervous system[41]. BDNF is a neural-related protein encoded early during
the embryonic period and its genome is made of eight promoters, each of which binds to a common BDNF fulllength protein-encoding exon [57]. Transcription of BDNF
is regulated by several mechanisms [58–60]. For example,
the cAMP response element-binding protein (CREB) controls the transcription of exon IV and it is a key factor forthe synaptic plasticity of neurons and cognition [61–64]. Furthermore, forskolin is a cAMP-elevating agent that canupregulate the expression of BDNF [65]. Recent studies haveshown that the use of BDNF has a positive impact on synaptic plasticity, neuron-glia communication, and regulation ofneurite outgrowth [66, 67]. The neuron-glia communicationis the foundation of neural maintenance. Glial cells canupregulate the expression of BDNF by receiving the signals
from neurons [67–69].

3
4.2. The Microenvironment Regulation of ASCs. ASCs canimprove the microenvironment for neural regeneration by
inhibiting inﬂammatory responses [70]. Inﬂammation is
induced by proinﬂammatory immune cells and cytokines
and ASCs can secrete angiogenic factors to inhibit that process [71–74]. The newborn blood vessels ameliorate themicroenvironment for tissue recovery while the inhibitionof angiogenesis aggravates the progression and pathology of
inﬂammation [75]. Black et al. found that ASCs reduced
inﬂammatory response and demonstrated positive therapeutic eﬀects on chronic inﬂammatory bowel disease in dogs[76]. ASCs can inhibit neural cell apoptosis by releasing
anti-inﬂammatory factors and cytokines, which provide astable microenvironment for the neural diﬀerentiation ofASCs [77].
The main anti-inﬂammatory factors secreted by ASCs
include tumour necrosis factor-inducible gene 6 protein(TSG-6) and STC-1 [78–81]. TSG-6 is a component of thenegative feedback mechanism and it can downregulate theinﬂammatory response [82]. Increasing evidences indicatethat some paracrine factors secreted by ASCs are enoughto alleviate inﬂammatory diseases in animal neural diseasemodels [78, 80, 83, 84]. The anti-inﬂammatory and immunomodulatory eﬀects of these cytokines and chemokines
are not only aﬀected by the status of ASCs but are also
aﬀected by the concentration of TGF-β1, tumour necrosis
factor-α (TNF-α), lipopolysaccharide (LPS), and hypoxia in
microenvironments [85–88]. Taken together, the interaction
between the neural diﬀerentiation of ASCs and the regulation of the microenvironment has a positive inﬂuence on
inﬂammatory inhibition.
4.3. The Regulation of Signaling Pathways. Since the discovery of the signaling pathways was introduced, scientists havediscovered that most of cell physiology can be explained by
the regulation of signaling pathways. The neural diﬀerentiation of ASCs is also regulated by multiple signaling pathways.
Here, we reviewed several known signaling pathways
involved in the neural diﬀerentiation process.
Researchers have discovered that the Wnt signaling pathway is involved in the formation of the brain. The
Wnt/LEF/TCF genes work synergistically to participate in
the development of the hippocampal gyrus, and Wnt3aknockout can stop the development of hippocampus inmouse embryos [89–91]. In addition, the Wnt signaling
pathway is also involved in the initiation of axon formation.
Wnt7a can induce the reconstitution of axons and growthcones in mossy nerve ﬁbers, as well as the collection of receptors I [91]. In contrast, Jang et al. have demonstrated that theclassical Wnt signaling pathway does not regulate the neuraldiﬀerentiation of ASCs. Instead, they have proved that the
noncanonical Wnt signaling pathway activates the neural differentiation of ASCs by regulating the activation/phosphorylation of Wnt5a/JNK signaling pathway [92].
Some other signaling pathways have been found to participate in the neural diﬀerentiation process, such as ROCK
and BDNF/TrkB signaling pathway. Ren et al. have provedthat the ROCK pathway inhibitor, namely, Y-27632, could
accelerate the neural diﬀerentiation of ASCs in their

4experiment. After adding Y-27632 into the culture medium,the shape of mouse ASCs switched to neuronal-like cells.
Furthermore, the cells lost their neuron-like morphology
once Y-27632 was removed from the medium [93]. It indicates that the ROCK signaling pathway inhibits the neuraldiﬀerentiation of ASCs. Some scholars have pointed out that
ASCs may be also regulated by the BDNF/TrkB signaling
pathway during the neural diﬀerentiation [84]. The
BDNF/TrkB signaling pathway induces the secretion of
BDNF which is a neurotrophic factor which can promote
the neural diﬀerentiation of ASCs as previously mentioned[85]. However, scientists are not sure how these multiple signaling pathways interplay in the neural diﬀerentiation ofASCs. More research is needed in this ﬁeld.

5. The Prospects for Clinical Application ofASCs in Neural Disease
Due to the limited therapeutic eﬀect of clinical methods,
treatment for nerve injury cannot keep pace with the life
quality of people. Many elderly people suﬀer from nervous
system diseases around the world. For example, the organic
chemical pollution in water always causes serious nervous
system diseases in developing countries and backward
regions. Nerve injury not only leads to neurological disorders
but also musculoskeletal system damage. Taking into
account the limitations of current therapeutic methods, theapplication of stem cell-based therapy is extremely urgent.
The occurrence of neurodegenerative diseases involves avariety of pathophysiological mechanisms that determine
the progress and severity of the diseases including neuroinﬂammation, mitochondrial dysfunction, and protein aggregation [94]. There are several common neurodegenerative
diseases in the clinic, such as AD, PD, TBI, and spinal cord
injury (SCI). In addition to their own ability to diﬀerentiate
into nerve cells, ASCs can also secrete various neurotrophic
factors and immune regulatory mediators. In the recent
years, clinical application of ASCs has attracted much attention in the ﬁeld of regenerative medicine.
5.1. AD. AD is a neurological degenerative disease withfamily heritability [95]. It is characterized by generalized
dementia, such as memory impairment, loss of recognition,
abnormal motion, and personality and behavioural change.
AD may be a heterogeneous group of diseases, which is regulated by a variety of factors, including biological and psychosocial factors. Entanglement of amyloid-β plaques andneuronal ﬁbers, neurodegeneration of the limbic system,and neural progressive decline are the main pathological features of AD [96].
Kim et al. have proved that the application of ASCs in the
AD mouse experimental models was feasible [97]. In theirstudy, the Morris water maze test (MWM) of mice was significantly improved. They found that Aβ plaque formations
were reduced in the cerebral cortex. Amyloid precursor protein (APP) levels were reduced and Aβ-degrading enzyme
levels were also upregulated. These phenomena clearly
showed that the symptom of AD has been ameliorated. In
another experiment, ASCs increased the secretion of anti-

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inﬂammatory factors, enhancing the expression of Aβdegrading enzymes and raising the response levels in cognitive and memory tests [38]. Furthermore, ASCs increased
the secretion of interleukin-10 and induced microglia topolarize the activation phenotype as well as express several
vascular and neurotrophic factors [38, 97, 98]. In the recent
years, Pérez-González et al. found that ASCs could secrete
leptin during neural diﬀerentiation. Leptin is a kind of protein hormone which promotes the neural regeneration ofstem cells in vitro and slows down the process of neurodegenerative diseases in vivo [99].
5.2. PD. PD is a common degenerative disease of the nervous
system in the elderly. The main pathological features of PD
are progressive dopaminergic neuron loss in the substantia
nigra pars compacta. Tremor, muscle rigidity, and decreased
motion are the main clinical features of PD. Zhang et al. havefound that PD patients always had chest muscle tissue tension which lead to breath function disorder [100]. It showsthat the nervous system damage of PD is not the most fatal
factor for patients. Dyspnea and its complications caused
by PD are the greatest harm to the human body.
In animal experimental models of PD, ASCs upregulated
the secretion of soluble growth factors including antiinﬂammatory factors and BDNF [101]. BDNF is an important neurotropic factor which can promote diﬀerentiationof stem cells and anti-inﬂammatory can improve the microenvironment as described earlier. The ASC-based regenerative therapy has a huge potential to treat PD and provides
us a new strategy to improve neural and musculoskeletal tissue function for PD patients. However, Schwerk et al. foundthat the function of regenerative dopaminergic neurons
induced by ASCs cannot completely replace that of lost dopaminergic neurons [102]. Furthermore, some scientists demonstrated that ASCs cannot improve the survival rate of PD
patients after clinical treatment [103]. More research is
required to clarify whether ASCs are useful in the treatmentof PD.
5.3. SCI. SCI is one of the common symptoms in serious
traumas caused by car accidents or falls. Serious injury
to the limbs and muscle atrophy due to disconnection
between muscles and damaged nerves disturb the ordinary
life of patients. Thousands of SCI patients impose a hugeburden on the development of social economy, and it
costs billions of dollars every year [1]. The prevention,
treatment, and rehabilitation of SCI have become a major
issue in the medical ﬁeld due to its urgency for patientsand society.
Some studies have shown that ASCs can survive andmigrate to damaged nerve tissue in animal experimental
models [104]. Meanwhile, transplanted ASCs express GFAP
and neuronal nuclear antigens in ischaemic encephalopathy[105]. In a previous study, the expression of GFAP, NF160,
and Tuj-1 of ASCs was positive after transplanted ASCs wereinserted into lentiviral vectors that were GFP-tagged in SCI
models [8]. It is suggested that the implantation of ASCs
can diﬀerentiate into astrocytes and oligodendrocytes as well
as neurons. Neurons deriving from diﬀerentiation can

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convey regenerative information from proximal-disruptingending neural ﬁbers to the distal side [106].
The neural regeneration in SCI has a positive eﬀect on
innervation to muscle after peripheral nerve injury. Whenthe peripheral nerve breaks down, the skeletal muscle
which is innervated by the damaged nerve degenerates
and muscle atrophy occurs. The neural transdiﬀerentiation process may be the consequence of cytokine secretion, the interactions of ASCs and intercellular signaling
pathways of ASCs [107]. Also, ASCs have been shownto secrete a variety of angiogenic and antiapoptotic cytokines,
which support tissue regeneration and minimize tissue
damage [108].
5.4. TBI. TBI is a type of disruption or alteration of brain
function caused by external forces. Skull fracture and intracranial hypertension caused by TBI can lead to conscious
disturbance, headache, and vomiting which are transientor long-lasting clinical symptoms of patients. External
forces that cause TBI include acceleration or deceleration,
direct compression, penetration of objects, and explosion
damage. In the United States, the top three causes of TBI
are fall (28%), motor vehicle accidents (20%), and pedestrian impact (19%) [109]. Masel and Dewitt thought that
TBI is a cascade process involving primary and secondary
brain injury instead of a simple external force injury process[110]. Primary damage refers to mechanical damage to thebrain tissue caused by external forces. Secondary damage
is a cellular metabolic event that occurs after an external
force injury [111]. Within 24 hours after the brain tissue
injury, the blood-brain barrier has been damaged andinﬂammatory cells enter the brain tissue leading to theoccurrence of inﬂammation.
Tajiri et al. have proved that ASCs and ASC-associatedsecreted proteins can reduce cortical damage in mouse TBI
models [112]. But the experimental mice were killed at an
early stage, and the relevant mechanisms have not been
proved. However, a possible mechanism is increasingly supported in scholars: inﬂammatory suppression theory [113].
Regarding these patients suﬀering TBI, inﬂammatory cells
release kinds of immune-mediated factors. It is often considered as a secondary brain injury [114, 115]. TNF-α, as a kindof inﬂammatory factor, mainly predominates the inﬂammatory response [116, 117]. Controlling the inﬂammatory
response after injury can be thought as a target for the
TBI treatment. Kappy et al. have demonstrated that ASCs
and its own secreting proteins downregulate the secretionof inﬂammatory factors and inhibit the inﬂammation in
TBI [118–120].
Furthermore, β-APP is thought to be an important
marker of nerve damage [121]. β-APP is a complete membrane protein with a high concentration in neuronal synapses. The role of β-APP in the brain has not been clariﬁed,
but the concentration of β-APP has been found increasingin the mouse TBI model [121]. β-APP can be used as amarker for diagnosing nerve damage and assessing the severity of TBI [122]. In Kappy’s experiment, inserting ASCs into
TBI mouse maintains the β-APP concentration instead ofmaking the concentration of β-APP continuously increasing

5[118]. It suggests that ASCs play a neuroprotective role in the
TBI model.

6. Conclusion
Stem cells have great abilities of multidirectional diﬀerentiation and are widely found in nearly all organs and tissues
except the heart. When human tissues or organs are damaged
or diseased, stem cells can diﬀerentiate into corresponding
progenitor cells and replenish the cell pools to recover normal function of organs. However, due to the particularity of
the nervous system, nerves are less able to self-regenerate.
The nerve injury is not only limited to the nerve tissues but
also often aﬀects the musculoskeletal tissues. Muscle atrophyand scar formation can be eﬀectively prevented by neuralregeneration. At present, the clinical therapy for neurodegenerative diseases mainly includes surgical and nonsurgicalmeans, such as neurolysis, direct nerve suture, and drug
treatment. Although these methods have been proved to havea degree of curative eﬀect, it has not lived up to expectations.
In recent years, stem cell-based therapies are expected toreplace orthodox treatment.
ASCs that are isolated from adipose tissue can diﬀerentiate into other kinds of cells with a low mortality rate in vivo
and in vitro. ASCs have advantages of easy material extraction, which means that they could be extracted from many
types of tissues with slight damage to the body. Most importantly, ASCs are characterized by low immunogenicity andare not susceptible to immune rejection. Considering theadvantages above, we are looking forward to a fact that ASCs
will play a crucial role in the treatment of various tissue andorgan diseases. In particular, in the nervous system, ASCs areimportant for promoting neural regeneration. The neurogenic and osteogenic diﬀerentiation of ASCs accelerates therecovery of damaged tissues. It will provide a new method
for orthodox treatments. However, there are still many issues
in the ﬁeld of neural regeneration with ASCs. For example,
the neural diﬀerentiation ability of ASCs extracted from different tissues should be clariﬁed in order to identify the mosteﬃcacious ASC source for neural regeneration. Moreresearch is needed in the ﬁeld for clinical application. We
truly believe that ASCs would play a signature role for neuralregeneration in the future.

Abbreviations
AD:
APP:
ASCs:
BDNF:
BM-MSCs:
CNS:
CNTF:
CREB:
DPSCs:
FDSCs:
FGF:
GDNF:
GFAP:

Alzheimer’s disease
Amyloid precursor protein
Adipose stem cells
Brain-derived neurotrophic factor
Bone marrow mesenchymal stem cells
Central nervous system
Ciliary neurotrophic factor
cAMP response element-binding protein
Dental pulp stem cells
Fetal-derived stem cells
Fibroblast growth factor
Glial-derived neurotrophic factor
Glial ﬁbrillary acidic protein

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HGF:
Hepatocyte growth factor
HFSCs:
Hair follicle stem cells
hPCy-MSCs: Human apical cyst-mesenchymal stem cells
iPSCs:
Induced pluripotent stem cells
LPS:
Lipopolysaccharide
MSCs:
Mesenchymal stem cells
MWM:
Morris water maze test
NeuN:
Neuronal nuclei protein
NGF:
Nerve growth factor
NSCs:
Neural stem cells
OEC-CM:
Olfactory ensheathing cell conditioned medium
PD:
Parkinson’s disease
PNS:
Peripheral nervous system
SC-CM:
Schwann cell conditioned medium
SCI:
Spinal cord injury
SESCs:
Skin epidermal stem cells
SSCs:
Skeletal stem cells
SVF:
Stromal vascular fraction
TBI:
Traumatic brain injury
TGF-β:
Transforming growth factor-β
TNF-α:
Tumour necrosis factor-αTSG-6:
Tumour necrosis factor-inducible gene 6
protein
VEGF:
Vascular endothelial growth factor.

Conflicts of Interest
The authors declare no conﬂict of interests.

Acknowledgments
This work was supported by grants from the project of Science & Technology Department of Sichuan Province(2017SZ0094) and the project of Science & Technology
Bureau of Chengdu (2016-HM01-00071-SF).

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