Effects of mesenchymal stem cell on dopaminergic neurons,motor and memory functions in animal models of Parkinson's disease:a systematic review and meta-analysis

Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.

Neural stem cells promote neuroplasticity: a promising therapeutic strategy for the treatment of Alzheimer’s disease

Recent studies have demonstrated that neuroplasticity,such as synaptic plasticity and neurogenesis,exists throughout the normal lifespan but declines with age and is significantly impaired in individuals with Alzheimer’s disease.Hence,promoting neuroplasticity may represent an effective strategy with which Alzheimer’s disease can be alleviated.Due to their significant ability to self-renew,differentiate,and migrate,neural stem cells play an essential role in reversing synaptic and neuronal damage,reducing the pathology of Alzheimer’s disease,including amyloid-β,tau protein,and neuroinflammation,and secreting neurotrophic factors and growth factors that are related to plasticity.These events can promote synaptic plasticity and neurogenesis to repair the microenvironment of the mammalian brain.Consequently,neural stem cells are considered to represent a potential regenerative therapy with which to improve Alzheimer’s disease and other neurodegenerative diseases.In this review,we discuss how neural stem cells regulate neuroplasticity and optimize their effects to enhance their potential for treating Alzheimer’s disease in the clinic.

Wharton’s jelly mesenchymal stem cells: Future regenerative medicine for clinical applications in mitigation of radiation injury

Wharton’s jelly mesenchymal stem cells(WJ-MSCs)are gaining significant attention in regenerative medicine for their potential to treat degenerative diseases and mitigate radiation injuries.WJ-MSCs are more naïve and have a better safety profile,making them suitable for both autologous and allogeneic transplantations.This review highlights the regenerative potential of WJ-MSCs and their clinical applications in mitigating various types of radiation injuries.In this review,we will also describe why WJ-MSCs will become one of the most probable stem cells for future regenerative medicine along with a balanced view on their strengths and weaknesses.Finally,the most updated literature related to both preclinical and clinical usage of WJ-MSCs for their potential application in the regeneration of tissues and organs will also be compiled.

Allogeneic mesenchymal stem cells may be a viable treatment modality in cerebral palsy

BACKGROUND Cerebral palsy(CP)describes a group of disorders affecting movement,balance,and posture.Disturbances in motor functions constitute the main body of CP symptoms.These symptoms surface in early childhood and patients are affected for the rest of their lives.Currently,treatment involves various pharmacotherapies for different types of CP,including antiepileptics for epilepsy and Botox A for focal spasticity.However,none of these methods can provide full symptom relief.This has prompted researchers to look for new treatment modalities,one of which is mesenchymal stem cell therapy(MSCT).Despite being a promising tool and offering a wide array of possibilities,mesenchymal stem cells(MSCs)still need to be investigated for their efficacy and safety.AIM To analyze the efficacy and safety of MSCT in CP patients.METHODS Our sample consists of four CP patients who cannot stand or walk without external support.All of these cases received allogeneic MSCT six times as 1×106/kg intrathecally,intravenously,and intramuscularly using umbilical cord-derived MSCs(UC-MSC).We monitored and assessed the patients pre-and post-treatment using the Wee Functional Independence Measure(WeeFIM),Gross Motor Function Classification System(GMFCS),and Manual Ability Classification Scale(MACS)instruments.We utilized the Modified Ashworth Scale(MAS)to measure spasticity.RESULTS We found significant improvements in MAS scores after the intervention on both sides.Two months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046;four months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046;12 months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046.However,there was no significant difference in motor functions based on WeeFIM results(P>0.05).GMFCS and MACS scores differed significantly at 12 months after the intervention(P=0.046,P=0.046).Finally,there was no significant change in cognitive functions(P>0.05).CONCLUSION In light of our findings,we believe that UC-MSC therapy has a positive effect on spasticity,and it partially improves motor functions.

Neural stem cell-derived exosomes promote mitochondrial biogenesis and restore abnormal protein distribution in a mouse model of Alzheimer's disease

Mitochondrial dysfunction is a hallmark of Alzheimer’s disease.We previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of AP P/PS1 mice.Because Alzheimer’s disease affects the entire brain,further research is needed to elucidate alterations in mitochondrial metabolism in the brain as a whole.Here,we investigated the expression of several important mitochondrial biogenesis-related cytokines in multiple brain regions after treatment with neural stem cell-derived exosomes and used a combination of whole brain clearing,immunostaining,and lightsheet imaging to clarify their spatial distribution.Additionally,to clarify whether the sirtuin 1(SIRT1)-related pathway plays a regulatory role in neural stem cell-de rived exosomes interfering with mitochondrial functional changes,we generated a novel nervous system-SIRT1 conditional knoc kout AP P/PS1mouse model.Our findings demonstrate that neural stem cell-de rived exosomes significantly increase SIRT1 levels,enhance the production of mitochondrial biogenesis-related fa ctors,and inhibit astrocyte activation,but do not suppress amyloid-βproduction.Thus,neural stem cell-derived exosomes may be a useful therapeutic strategy for Alzheimer’s disease that activates the SIRT1-PGC1αsignaling pathway and increases NRF1 and COXIV synthesis to improve mitochondrial biogenesis.In addition,we showed that the spatial distribution of mitochondrial biogenesis-related factors is disrupted in Alzheimer’s disease,and that neural stem cell-derived exosome treatment can reverse this effect,indicating that neural stem cell-derived exosomes promote mitochondrial biogenesis.

One-step cell biomanufacturing platform:porous gelatin microcarrier beads promote human embryonic stem cell-derived midbrain dopaminergic progenitor cell differentiation in vitro and survival after transplantation in vivo

Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s disease.However,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation niche.Here,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor cells.These beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in vitro.Importantly,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell grafts.Overall,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.

Long-term outcome of stem cell transplantation with and without anti-tumor necrotic factor therapy in perianal fistula with Crohn’s disease

BACKGROUND Stem cell transplantation is a promising therapeutic option for curing perianal fistula in Crohn’s disease(CD).Anti-tumor necrotic factor(TNF)therapy combined with drainage procedure is effective as well.However,previous studies are limited to proving whether the combination treatment of biologics and stem cell transplantation improves the effect of fistula closure.AIM This study aimed to evaluate the long-term outcomes of stem cell transplantation and compare Crohn’s perianal fistula(CPF)closure rates after stem cell transplantation with and without anti-TNF therapy,and to identify the factors affecting CPF closure and recurrence.METHODS The patients with CD who underwent stem cell transplantation for treating perianal fistula in our institution between Jun 2014 and December 2022 were enrolled.Clinical data were compared according to anti-TNF therapy and CPF closure.RESULTS A total of 65 patients were included.The median age of females was 26 years(range:21-31)and that of males was 29(44.6%).The mean follow-up duration was 65.88±32.65 months,and complete closure was observed in 50(76.9%)patients.The closure rates were similar after stem cell transplantation with and without anti-TNF therapy(66.7%vs 81.6%at 3 year,P=0.098).The patients with fistula closure had short fistulous tract and infrequent proctitis and anorectal stricture(P=0.027,0.002,and 0.008,respectively).Clinical factors such as complexity,number of fistulas,presence of concurrent abscess,and medication were not significant for closure.The cumulative 1-,2-,and 3-year closure rates were 66.2%,73.8%,and 75.4%,respectively.CONCLUSION Anti-TNF therapy does not increase CPF closure rates in patients with stem cell transplantation.However,both refractory and non-refractory CPF have similar closure rates after additional anti-TNF therapy.Fistulous tract length,proctitis,and anal stricture are risk factors for non-closure in patients with CPF after stem cell transplantation.

Potential plausible role of Wharton’s jelly mesenchymal stem cells for diabetic bone regeneration

This letter addresses the review titled“Wharton’s jelly mesenchymal stem cells:Future regenerative medicine for clinical applications in mitigation of radiation injury”.The review highlights the regenerative potential of Wharton’s jelly mesenchymal stem cells(WJ-MSCs)and describes why WJ-MSCs will become one of the most probable stem cells for future regenerative medicine.The potential plausible role of WJ-MSCs for diabetic bone regeneration should be noticeable,which will provide a new strategy for improving bone regeneration under diabetic conditions.

Future directions:combination of acupuncture with mesenchymal stem cells for Parkinson’s disease

Parkinson’s disease(PD)is a progressive chronic disease currently with no radical cure drugs and means due to the complex pathological mechanisms and limited regenerative capacity of neurons.Acupuncture aids in neuronal regeneration via various signaling routes like ROCK,Wnt,and Notch,safeguarding dopaminergic neurons against inflammation,oxidative stress,and cell death,which in turn enhances the progression of PD progression.Numerous research findings indicate that integrating acupuncture with mesenchymal stem cells(MSCs)transplantation is more effective than using either acupuncture or MSCs infusion alone.The combined treatment improves the survival rate of MSCs,promotes the generation of functional neural networks by stimulating the secretion of neurotrophic factors,and ultimately improves the disease microenvironment.In this review,we state the neuroprotective effects of acupuncture or MSCs treament alone in PD,then summarize the application of acupuncture combined with MSCs therapy in other diseases.Consequently,we anticipate that integrating acupuncture with MSCs transplantation may emerge as a novel and efficient approach for managing PD.This possibility needs to be verified through further basic and clinical research.

Effect of Different Chemical Treatments on Seedling Emergence Growth of Frozen Cassava

The rooting and growth of frozen cassava under different chemical treatments were studied.The result has demonstrated that disinfection effect could increase rooting rate and seedling emergence rate of cassava seed stem and decrease the rate of mildew.The sportak treatment could generate better effect(rooting rate and seedling emergence rate were 63%,the mildew rate of stem was 28%).Among different rooting reagents,Genwang+lime treatment generated better effect on rooting rate and emergence rate of frozen cassava than these of other groups and control group.It was concluded from the effects of different rooting reagents on growth of seed stem that Genwang+lime treatment could promote elongation and growth of cassava significantly(the mean plant height of experimental groups inceased 8.58 cm compared with that of control group) while paclobutrazol+lime generated the best effect on crassation of stem(the stem diameter of experimental group increased 0.4 cm compared with that of control group).

美国STEM教育计划对我国科技创新人才培养的启示及建议

在分析美国推动STEM(科学、技术、工程和数学)教育的时代背景、发展特点和成效的基础上,研究美国集合社会各方面力量、多部门协同推进STEM教育的组织协调机制,为我国创新型人才培养和工程技术、创新教育开展提供经验借鉴。就确立创新型人力资源在国家未来发展中的战略地位、部门协同和动员全社会资源参与、加快我国教育和科技体制改革步伐等三个方面提出政策启示和建议。

STEM-X的急性毒性与抗肿瘤活性实验研究

目的研究STEM-X的急性毒性和体内对肿瘤的抑制作用。方法采用急性毒性实验:选取昆明种小鼠30只,随机分为3组,每组10只。禁食24h后一次性给药。给药后连续观察14d,详细记录小鼠的死亡数目、死亡时间及主要毒性反应。抗肿瘤实验:建立S180荷瘤小鼠模型40只,随机分为4组,每组10只,即低剂量药物组(浓缩液10mL.kg-1),高剂量药物组浓缩液(20mL.kg-1),氟尿嘧啶(5-Fu)阳性对照组(20mg·kg-1),空白对照组。连续灌胃给药10d,处死动物,称重,完整剥离瘤块并称瘤重。计算肿瘤抑制率。结果急性毒性实验的3个剂量组均未出现小鼠死亡,无明显异常。STEM-X浓缩液的半数致死量(LD50)>50mL.kg-1。抗肿瘤活性实验中,高、低剂量组、阳性对照组的瘤重和空白组比较,差异有显著性。高剂量组的肿瘤抑制率和阳性对照组比较,差异无显著性。低剂量组和阳性对照组比较,差异有显著性。结论STEM-X在正常剂量下,安全、毒副作用极低。对S180肉瘤有明显抑制作用。

Research progress and prospects of markers for liver cancer stem cells

Liver cancer is a common malignancy and surgery is the main treatment strategy. However, the prognosis is still poor because of high frequencies of postoperative recurrence and metastasis. In recent years, cancer stem cell(CSC) theory has evolved with the concept of stem cells, and has been applied to oncological research. According to cancer stem cell theory, liver cancer can be radically cured only by eradication of liver cancer stem cells(LCSCs). This notion has lead to the isolation and identification of LCSCs, which has become a highly researched area. Analysis of LCSC markers is considered to be the primary method for identification of LCSCs. Here, we provide an overview of the current research progress and prospects of surface markers for LCSCs.

WJSC 6^(th) Anniversary Special Issues(2):Mesenchymal stem cells Umbilical cord-derived mesenchymal stem cells:Their advantages and potential clinical utility

Human umbilical cord(UC)is a promising source of mesenchymal stem cells(MSCs).Apart from their prominent advantages,such as a painless collection procedure and faster self-renewal,UC-MSCs have shown the ability to differentiate into three germ layers,to accumulate in damaged tissue or inflamed regions,to promote tissue repair,and to modulate immune response.There are diverse protocols and culture methods for the isolation of MSCs from the various compartments of UC,such as Wharton’s jelly,vein,arteries,UC lining and subamnion and perivascular regions.In this review,we give a brief introduction to various compartments of UC as a source of MSCs and emphasize the potential clinical utility of UC-MSCs for regenerative medicine and immunotherapy.

Decreased osteogenesis of adult mesenchymal stem cel s by reactive oxygen species under cyclic stretch: a possible mechanism of age related osteoporosis

Age related defect of the osteogenic differentiation of mesenchymal stem cells（MSCs） plays a key role in osteoporosis. Mechanical loading is one of the most important physical stimuli for osteoblast differentiation.Here, we compared the osteogenic potential of MSCs from young and adult rats under three rounds of 2 h of cyclic stretch of 2.5% elongation at 1 Hz on 3 consecutive days. Cyclic stretch induced a significant osteogenic differentiation of MSCs from young rats, while a compromised osteogenesis in MSCs from the adult rats.Accordingly, there were much more reactive oxygen species（ROS） production in adult MSCs under cyclic stretch compared to young MSCs. Moreover, ROS scavenger N-acetylcysteine rescued the osteogenic differentiation of adult MSCs under cyclic stretch. Gene expression analysis revealed that superoxide dismutase 1（SOD1） was significantly downregulated in those MSCs from adult rats. In summary, our data suggest that reduced SOD1 may result in excessive ROS production in adult MSCs under cyclic stretch, and thus manipulation of the MSCs from the adult donors with antioxidant would improve their osteogenic ability.

Mesenchymal stem cell-derived exosomes promote neurogenesis and cognitive function recovery in a mouse model of Alzheimer’s disease

Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment.The purpose of this study was to investigate the effects of mesenchymal stem cell-derived exosomes on neurogenesis and cognitive capacity in a mouse model of Alzheimer’s disease.Alzheimer’s disease mouse models were established by injection of beta amyloid 1?42 aggregates into dentate gyrus bilaterally.Morris water maze and novel object recognition tests were performed to evaluate mouse cognitive deficits at 14 and 28 days after administration.Afterwards,neurogenesis in the subventricular zone was determined by immunofluorescence using doublecortin and PSA-NCAM antibodies.Results showed that mesenchymal stem cells-derived exosomes stimulated neurogenesis in the subventricular zone and alleviated beta amyloid 1?42-induced cognitive impairment,and these effects are similar to those shown in the mesenchymal stem cells.These findings provide evidence to validate the possibility of developing cell-free therapeutic strategies for Alzheimer’s disease.All procedures and experiments were approved by Institutional Animal Care and Use Committee(CICUAL)(approval No.CICUAL 2016-011)on April 25,2016.

Stem cell injection for complex anal fistula in Crohn’s disease: A single-center experience

BACKGROUND Despite tremendous progress in medical therapy and optimization of surgical strategies,considerable failure rates after surgery for complex anal fistula in Crohn’s disease have been reported.Therefore,stem cell therapy for the treatment of complex perianal fistula can be an innovative option with potential long-term healing.AIM To evaluate the results of local administration of allogenic,adipose-derived mesenchymal stem cells(darvadstrocel)for complex anal Crohn’s fistula.METHODS All patients with complex anal fistulas associated with Crohn’s disease who were amenable for definite fistula closure within a defined observation period were potential candidates for stem cell injection(darvadstrocel)if at least one conventional or surgical attempt to close the fistula had failed.Darvadstrocel was only indicated in patients without active Crohn’s disease and without presence of anorectal abscess.Local injection of darvadstrocel was performed as a standardized procedure under general anesthesia including single-shot antibiotic prophylaxis,removal of seton drainage,fistula curettage,closure of the internal openings and local stem cell injection.Data collection focusing on healing rates,occurrence of abscess and follow-up was performed on a regular basis of quality control and patient care.Data were retrospectively analyzed.RESULTS Between July 2018 and January 2021,12 patients(6 females,6 males)with a mean age of 42.5(range:26-61)years underwent stem cell therapy.All patients had a minimum of one complex fistula,including patients with two complex fistulas in 58.3%(7/12).Two of the 12 patients had horse-shoe fistula and 3 had one complex fistula.According to Parks classification,the majority of fistulas were transsphincteric(76%)or suprasphincteric(14%).All patients underwent removal of seton,fistula curettage,transanal closure of internal opening by suture(11/12)or mucosal flap(1/12)and stem cell injection.At a mean follow-up of 14.3(range:3-30)mo,a healing rate was documented in 66.7%(8/12);mean duration to achieve healing was 12(range:6-30)wk.Within follow-up,4 patients required reoperation due to perianal abscess(33.3%).Focusing on patients with a minimum follow-up of 12 mo(6/12)or 24 mo(4/12),long-term healing rates were 66.7%(4/6)and 50.0%(2/4),respectively.CONCLUSION Data of this single-center experience are promising but limited due to the small number of patients and the retrospective analysis.

Effects of cotransplantated Schwann cells and neural stem cells in a rat model of Alzheimer's disease

Schwann cells （SCs） are significantly better at promoting neural stem cell （NSCs） proliferation, differentiation and synaptic formation when cocultured with NSCs in vitro, compared with cultured in a single nerve growth factor. The present study transplanted NSCs and SCs into the brain of a rat model of Alzheimer＇s disease to investigate the effect of cotransplantation. Results show transplantation of both NSCs alone and NSCs ＋ SCs significantly promoted learning and memory functions in Alzheimer＇s disease rats, decreased glial fibrillary acidic protein and calcium binding protein S100β expression, but increased expression of the cholinergic neuron marker choline acetyl transferase mRNA. The effect of NSCs ＋ SCs cotransplantation was, however, more significant. NSCs and SCs cotransplantation significantly reduced the number of astrocytes and increased cholinergic neurons, facilitating the recovery of learning and memory function, compared with NSCs transplantation alone.

Protective effects of transplanted neural stem cells on the brain of Alzheimer’s disease rats

BACKGROUND： To date, no drugs are able to halt the progression of Alzheimer＇s disease （AD）. Neural stem cells （NSCs） transplantation has been widely used to treat AD, but the mechanism of AD treatment remains unclear. OBJECTIVE： To observe changes in protein and factors in the hippocampus and frontal lobe of AD rats following NSCs transplantation, and to understand mechanism of action of NSCs transplantation in AD treatment. DESIGN, TIME AND SETTING： A randomized, controlled animal study was conducted at the First Clinical Hospital, Jilin University, China from July 2007 to March 2009. MATERIALS： NSCs were harvested from the hippocampus of 10 E16 Wistar rats. METHODS： A total of 57 male adult Wistar rats were equally and randomly divided into normal control, AD model and NSCs groups. AD models were established in the AD model and NSCs groups by bilateral removal of hippocampus. At 2 weeks postsurgery, NSCs were transplanted into the hippocampus of rats from the NSCs group. MAIN OUTCOME MEASURES： Protein levels were measured in the hippocampus of rats from normal control, NSCs and AD model groups using proteomics. Expression of choline acetyl transferase mRNA, glial fibrillary acidic protein and S100β was measured in the hippocampus and frontal lobe of rats using in situ hybridization and immunohistochemistry. RESULTS： Expression of choline acetyl transferase mRNA, heat shock protein 70, heat shock protein 90, F-actin and actin was significantly higher in the NSCs group compared with AD model group. Glial fibrillary acidic protein and S100β expression was less in the NSCs group compared with AD model group. CONCLUSlOIN： NSCs implanted into the brain may generate new neural cells, which can relieve damage to the cholinergic system and resist apoptosis. NSCs transplantation plays a protective role in the cholinergic system in the AD rats to some extent.

Stem cell therapy for Parkinson’s disease: safety and modeling

For decades,clinicians have developed medications and therapies to alleviate the symptoms of Parkinson’s disease,but no treatment currently can slow or even stop the progression of this localized neurodegeneration.Fortunately,sparked by the genetic revolution,stem cell reprogramming research and the advancing capabilities of personalization in medicine enable forward-thinking to unprecedented patient-specific modeling and cell therapies for Parkinson’s disease using induced pluripotent stem cells(iPSCs).In addition to modeling Parkinson’s disease more accurately than chemically-induced animal models,patient-specific stem cell lines can be created,elucidating the effects of genetic susceptibility and sub-populations’differing responses to in vitro treatments.Sourcing cell therapy with iPSC lines provides ethical advantages because these stem cell lines do not require the sacrifice of human zygotes and genetically-specific drug trails can be tested in vitro without lasting damage to patients.In hopes of finally slowing the progression of Parkinson’s disease or re-establishing function,iPSC lines can ultimately be corrected with gene therapy and used as cell sources for neural transplantation for Parkinson’s disease.With relatively localized neural degeneration,similar to spinal column injury,Parkinson’s disease presents a better candidacy for cell therapy when compared to other diffuse degeneration found in Alzheimer’s or Huntington’s Disease.Neurosurgical implantation of pluripotent cells poses the risk of an innate immune response and tumorigenesis.Precautions,therefore,must be taken to ensure cell line quality before transplantation.While cell quality can be quantified using a number of assays,a yielding a high percentage of therapeutically relevant dopaminergic neurons,minimal de novo genetic mutations,and standard chromosomal structure is of the utmost importance.Current techniques focus on iPSCs because they can be matched with donors using human leukocyte antigens,thereby reducing the severity and risk of immune rejection.In August of 2018,researchers in Kyoto,Japan embarked on the first human clinical trial using iPSC cell therapy transplantation for patients with moderate Parkinson’s disease.Transplantation of many cell sources has already proven to reduce Parkinson’s disease symptoms in mouse and primate models.Here we discuss the history and implications for cell therapy for Parkinson’s disease,as well as the necessary safety standards needed for using iPSC transplantation to slow or halt the progression of Parkinson’s disease.