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.

Safety and efficiency of Wharton’s Jelly-derived mesenchymal stem cell administration in patients with traumatic brain injury:First results of a phase I study

BACKGROUND Traumatic brain injury(TBI)is characterized by a disruption in the normal function of the brain due to an injury following a trauma,which can potentially cause severe physical,cognitive,and emotional impairment.Stem cell transplantation has evolved as a novel treatment modality in the management of TBI,as it has the potential to arrest the degeneration and promote regeneration of new cells in the brain.Wharton’s Jelly-derived mesenchymal stem cells(WJ-MSCs)have recently shown beneficial effects in the functional recovery of neurological deficits.AIM To evaluate the safety and efficiency of MSC therapy in TBI.METHODS We present 6 patients,4 male and 2 female aged between 21 and 27 years who suffered a TBI.These 6 patients underwent 6 doses of intrathecal,intramuscular(i.m.)and intravenous transplantation of WJ-MSCs at a target dose of 1×106/kg for each application route.Spasticity was assessed using the Modified Ashworth scale(MAS),motor function according to the Medical Research Council Muscle Strength Scale,quality of life was assessed by the Functional Independence Measure(FIM)scale and Karnofsky Performance Status scale.RESULTS Our patients showed only early,transient complications,such as subfebrile fever,mild headache,and muscle pain due to i.m.injection,which resolved within 24 h.During the one year follow-up,no other safety issues or adverse events were reported.These 6 patients showed improvements in their cognitive abilities,muscle spasticity,muscle strength,performance scores and fine motor skills when compared before and after the intervention.MAS values,which we used to assess spasticity,were observed to statistically significantly decrease for both left and right sides(P<0.001).The FIM scale includes both motor scores(P<0.05)and cognitive scores(P<0.001)and showed a significant increase in pretest posttest analyses.The difference observed in the participants’Karnofsky Performance Scale values pre and post the intervention was statistically significant(P<0.001).CONCLUSION This study showed that cell transplantation has a safe,effective and promising future in the management of TBI.

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.

Structural and antioxidative properties of royal jelly protein by partial enzymatic hydrolysis

The objective of this study was to investigate the structural and antioxidative properties of royal jelly protein(RJP)at different degrees of hydrolysis(DH)by partial enzymatic hydrolysis. RJP was hydrolyzed by alcalase for 0 min, 15 min, 1 h, 5 h and 8 h to obtain hydrolysates at DH of 5.34%, 11.65%, 15.19%, 21.38% and 23.91%, respectively. With the increased DH, the RJP hydrolysates showed elevated antioxidative activities. The molecular weight of RJP hydrolysates was significantly decreased but their primary backbone kept unchanged. Analysis of circular dichroism spectra revealed that the enzymolysis reduced the content of α-helix but increased the contents of β-sheet, β-turn and random coil. Meanwhile, the surface hydrophobicity and fluorescence intensity of RJP hydrolysates were decreased and a red shift occurred. As the enzymolysis continued, the surface morphology of RJP was gradually changed from a sheet-like structure into microparticles. Changes in antioxidative activities and structures generally followed a DH-dependent manner, however these changes became insignificant for samples at DH beyond 20%. Taking into consideration of both effectiveness and productivity, the optimum enzymatic duration was determined at 5 h.

A Preliminary Study on Consumer Sensory Evaluation and Acceptance of Pomelo Peel Jelly

Pomelo peel is a by-product from pomelo consumption, but it is also rich in a variety of nutrients and functional substances. In order to solve the environmental problems caused by the large amount of discarded pomelo peels every year, in this study, we recycled pomelo peels to make pomelo yellow peel jelly (PYPJ) and pomelo white peel jelly (PWPJ) according to their different characteristics in pomelo peels. And the consumer sensory evaluation (n = 50) was carried out to explore the consumers’ evaluation and acceptance for these two innovative products. The results showed that both jellies received high mean scores for all sensory attributes expect PYPJ’ taste, and the consumer acceptances of PYPJ and PWPJ were 62% and 92%, respectively. These results displayed that there is a need to further improve PYPJ, and PWPJ is a product recognized by consumers. .

人脐带Wharton’s jelly源间充质干细胞培养中碱性成纤维细胞生长因子的作用

背景：培养脐带源间充质干细胞过程中,细胞形态常易变得宽大不规则,传代不易贴壁,死亡率高,找到一个维持细胞稳定的方法是有必要的。目的：拟采用组织块培养法从人脐带Wharton’s jelly中分离培养间充质干细胞,观察碱性成纤维细胞生长因子对其生物学特性的影响。方法：采用组织块法分离培养和扩增脐带组织间充质干细胞,对照组用DMEM/F12培养基＋体积分数为10%胎牛血清培养,实验组用DMEM/F12培养基＋体积分数为10%胎牛血清＋20μg/L碱性成纤维细胞生长因子培养。观察组织块游出细胞的时间和细胞形态,每隔3d或4d更换培养液,待细胞达到80%~90%融合时,用0.25%胰酶消化后,按1：2或1：3的比例传代。结果与结论：倒置显微镜下观察对照组中从8~10d开始有细胞从组织块四周游出贴壁,实验组中从6~8d开始有细胞从组织块四周游出贴壁,1周后可见多数呈长梭形或扁平形的成纤维样细胞,围绕组织块成旋涡状,前3代细胞形态及传代间隔时间两组基本相同;3代以后实验组细胞较对照组易于贴壁,传代死亡率低,生长曲线提示增殖能力强。流式细胞术分析两组细胞周期显示第3,6代70%以上的细胞处于G0/G1期,且第3,6代细胞均阳性表达CD29,CD44,弱表达HLA-ABC,不表达CD34、CD45和HLA-DR。结果提示采用组织块培养法可从人脐带Wharton’s jelly中分离出具有间充质干细胞特性的细胞,且碱性成纤维细胞生长因子能使细胞从组织块游出时间提前和有助于促使细胞贴壁,一定程度上维持细胞形态稳定性,提高增殖能力,并且不改变细胞的表面标志物表达。

Processing Technology of Pomelo jelly with Health-care Function

[Objective] The aim was to research the processing technology of pomelo jelly with health-care function. [Method] With Citrus maxima （Burm.） Merr. cv. Guanxiyou as the raw materials, the optimal processing technology of pomelo jelly with health-care function was obtained by orthogonal test based on the results of single factor test. [Result] The optimal processing technology of pomelo jelly with healthAugust 16, 2016care function was as follows： 30% pomelo juice, 15% sugar, 1.0% mixed gel and 0.19% citric acid. Under these conditions, the pomelo jelly had relatively good sensory status, with certain nutritional value and health care function. [Conclusion] This research provides references for the deep processing of pomelo.

“生物药”——Wharton's jelly源间充质干细胞

干细胞治疗代表生物冶疗进入到了一个崭新的时代。间充质干细胞是存在于胚胎或成体组织中来源于中胚层具有多向分化潜能的干细胞。由于成体间充质干细胞的质量与数量自身缺陷,使之应用受到了很大限制。Wharton's jelly组织,是起始于胚胎发育第13天的胚外中胚层组织。使用基因微阵列分析及功能分析,首次发现Wharton's jelly源间充质干细胞(Wharton's jelly derived mesenchymal stem cells,WJMSCs)高表达胚胎早期干性基因及心肌细胞分化早期特异转录因子,可分化心肌细胞等多种细胞。进而,应用临床级WJMSCs经冠状动脉移植治疗ST抬高型急性心肌梗死患者的随机双盲临床试验,首次证明WJMSCs可明显改善心肌活力及心脏功能。因此,WJMSCs具有极其重要益处;无伦理涉及,有强的分化潜能,无致瘤性;加之,WJMSCs可作为产品,在任何时候病情需要时立即应用。为此,WJMSCs作为真正意义上的干细胞族,将最有希望成为具有应用前景的于细胞生物药。

脐带Wharton’s jelly源间充质干细胞——细胞治疗理想选择

脐带Wharton’s jelly源间充质干细胞(WJ-MSCs)是原始的间充质干细胞,具有较强的自我更新及多向分化潜能,无致肿瘤性,同时具有较低的免疫原性,在临床前期多种疾病的防治中具有较好的作用。由于其取材方便,应用无伦理争议,是细胞治疗修复组织损伤的理想选择。文章就WJ-MSCs的性质及应用等做一综述。

人脐带Wharton’s Jelly来源间充质干细胞与人牙周膜干细胞成骨分化能力的对比研究

目的:比较人脐带Wharton’s Jelly来源间充质干细胞(human umbilical cord Wharton’s Jelly-derived mesechymal stem cells,h UCWJMSCs)与人牙周膜干细胞(periodontal mesenchymal stem cells,h PDLSCs)成骨分化能力。方法:体外培养h UCWJMSCs和h PDLSCs。MTT法检测细胞增殖情况;成骨诱导后测定细胞的ALP活性,茜素红染色检测细胞矿化能力,Real-time PCR分析OPN和Runx2基因的表达。结果:hUCWJMSCs增殖能力高于hPDLSCs;经矿化诱导后hPDLSCsALP表达、矿化结节形成高于hUCWJMSCs(P<0.05);Runx2在hPDLSCs中表达高于hUCWJMSCs(P<0.05);而hUCWJMSCs中OPN表达高于hPDLSCs(P<0.05)。结论:h UCWJMSCs、hPDLSCs均具有成骨分化能力,hPDLSCs成骨分化能力较强。

Human umbilical cord Wharton's jelly-derived oligodendrocyte precursor-like cells for axon and myelin sheath regeneration

Human umbilical mesenchymal stem cells from Wharton＇s jelly of the umbilical cord were induced to differentiate into oligodendrocyte precursor-like cells in vitro. Oligodendrocyte precursor cells were transplanted into contused rat spinal cords. Immunofluorescence double staining indicated that transplanted cells survived in injured spinal cord, and differentiated into mature and immature oligodendrocyte precursor cells. Biotinylated dextran amine tracing results showed that cell transplantation promoted a higher density of the corticospinal tract in the central and caudal parts of the injured spinal cord. Luxol fast blue and toluidine blue staining showed that the volume of residual myelin was significantly increased at 1 and 2 mm rostral and caudal to the lesion epicenter after cell transplantation. Furthermore, immunofluorescence staining verified that the newly regenerated myelin sheath was derived from the central nervous system. Basso, Beattie and Bresnahan testing showed an evident behavioral recovery. These results suggest that human umbilical mesenchymal stem cell-derived oligodendrocyte precursor cells promote the regeneration of spinal axons and myelin sheaths.

Wharton's jelly mesenchymal stem cells differentiate into retinal progenitor cells

Human Wharton＇s jelly mesenchymal stem cells were isolated from fetal umbilical cord. Cells were cultured in serumfree neural stem cellconditioned medium or neural stem cellconditioned medium supplemented with Dkk1, a Wnt/13 catenin pathway antagonist, and LeftyA, a Nodal signaling pathway antagonist to induce differentiation into retinal progenitor cells. Inverted microscopy showed that after induction, the spindleshaped or fibroblastlike Wharton＇s jelly mesenchymal stem cells changed into bulbous cells with numerous processes. Immunofluorescent cytochemical stain ing and reversetranscription PCR showed positive expression of retinal progenitor cell markers, Pax6 and Rx, as well as weakly downregulated nestin expression. These results demonstrate that Wharton＇s jelly mesenchymal stem cells are capable of differentiating into retinal progenitor cells in vitro.

人脐带Wharton's Jelly来源间充质干细胞和人牙周膜干细胞复合PHBHHx、PHBV支架成骨分化能力的体外研究

目的:探讨人脐带Wharton's Jelly来源间充质干细胞(h UCWJMSCs)和人牙周膜干细胞(h PDLSCs)复合聚(3-羟基丁酸酯-3-羟基己酸酯)(PHBHHx)、聚羟基丁酸-羟基戊酸酯(PHBV)支架成骨分化的能力。方法:将2种干细胞分别接种在2种支架中,MTT法及粘附率分析2种干细胞和PHBHHx、PHBV的生物相容性;成骨诱导后ALP活性检测、茜素红染色和扫描电镜观察研究两种干细胞在两种支架上的成骨分化情况。结果:2种干细胞与PHBV具有更好的黏附效果及增殖效率(P <0. 05),且h UCWJMSCs组优于h PDLSCs组; h UCWJMSCs和h PDLSCs与PHBV组ALP活性检测、茜素红染色阳性表达明显高于与PHBHHx组; h UCWJMSCs与2种支架组的表达高于h PDLSCs组。扫描电镜显示2种干细胞与PHBV组可见大量矿化基质形成。结论:h UCWJMSCs与PHBV生物相容性和成骨能力优于h PDLSCs组。

Differential volatile organic compounds in royal jelly associated with different nectar plants

The aim of this work was to distinguish volatile organic compound（VOC） profiles of royal jelly（RJ） from different nectar plants. Headspace solid-phase microextraction（HS-SPME） was used to extract VOCs from raw RJ harvested from 10 nectar plants in flowering seasons. Qualitative and semi-quantitative analysis of VOCs extracts were performed by gas chromatography-mass spectrometry（GC-MS）. Results showed that VOC profiles of RJ from the samples were rich in acid, ester and aldehyde compound classes, however, contents of them were differential, exemplified by the data from acetic acid, benzoic acid methyl ester, hexanoic acid and octanoic acid. As a conclusion, these four VOCs can be used for distinguishing RJ harvested in the seasons of different nectar plants.

Major royal jelly proteins accelerate onset of puberty and promote ovarian follicular development in immature female mice

The major royal jelly proteins(MRJPs)are the central constituents responsible for the specific activities of royal jelly.Here MRJPs via oral administration daily for 45 consecutive days were evaluated the effects on the reproductive parameters in immature female mice(FM).Neonatal FM were divided into four groups fed MRJPs with doses of 0,125,250 and 500 mg/kg/body weight(M125,M250 and M500).The results in M125,M250 and M500 showed that the times of estrus were accelerated by 10.7%,15.5%and 10.7%,the secondary follicles number were increased by 50.7%,78.8%and 38.6%,the Graafian follicles were increased by 600.0%and 774.0%and 150.0%,respectively.M500 induced multi-oocyte follicles.The serum estradiol levels of the three groups were increased by 47.1%,64.9%and 31.1%,the action of MRJPs raising hormone secretion level is mainly via upregulating expression of ERˇgene.Antioxidant parameters of ovarian tissue showed that the malondialdehyde levels in M125 and M250 were decreased,the superoxide dismutase activities and glutathione peroxidase activities in M125 and M250 were increased.In conclusion,MRJPs may accelerate onset of puberty and promote follicular development in FM.Our findings would facilitate better understanding of the benefit effect of MRJPs as the key ingredient in royal jelly on promoting fertility performance.

Royal-jelly-based apitherapy can attenuate damages to male reproductive parameter following nicotine administration

Background:Nicotine administration can generate severe oxidative stress and lipid peroxidation.Royal jelly,with its antioxidant properties,acts as a scavenger of reactive oxygen species.This study describes the apitherapy effects of royal jelly on testicular damage following nicotine administration.Methods:Forty-eight male BALB/c mice were divided into 8 groups(n=6):saline,3 different doses of royal jelly(100,150,and 200 mg/kg body weight(BW)per day),nicotine(1.5 mg/kg),and 3 different groups of Nic+Roy(1.5 mg/kg of Nic+100,150,and 200 mg/kg BW per day of royal jelly).Nicotine was administrated intraperitoneally,and royal jelly was prescribed orally for 10 consecutive days.Serum levels of hormones(testosterone,luteinizing hormone,and follicle-stimulating hormone),total antioxidant capacity,nitric oxide(NO)status,malondialdehyde levels,sperm DNA fragmentation,sperm parameters,histopathological changes(H&E staining),immunohistochemistry against apoptotic proteins,and gene expression of Bcl-2,p53,Caspase-3,and Nrf2(real-time PCR)were assessed to evaluate the molecular and histological changes.Results:Hormone levels,sperm parameters,and status of antioxidants were decreased significantly(p<.05)following nicotine administration.Moreover,royal jelly treatment normalized hormonal and antioxidant characteristics,decreased apoptotic gene expression,increased Nfr2 gene expression,and restored histopathological alteration to the physiological status significantly(p<.05).Conclusion:Royal jelly upregulates the antioxidant status,inhibits the mitochondrialdependent apoptosis pathway,and increases the rate of proliferation.This therapeutic agent effectively protected the testis against nicotine-associated damages by antioxidant and anti-apoptotic effects.

Human Wharton’s jelly mesenchymal stem cells inhibit cytokine storm in acute respiratory distress syndrome in a rat model

Objective:To evaluate the potential effect of human Wharton’s jelly mesenchymal stem cells(hWJMSCs)on acute respiratory distress syndrome in lipopolysaccharide(LPS)-induced rats.Methods:The hWJMSCs(5×10^(4)/mL,5×10^(5)/mL,5×10^(6)/mL)were administered to rats on day 1 and day 8 after being induced by LPS(5 mg/kg body weight).TNF-αlevels in the lung and IL-18 and IL-1βlevels in the serum were measured using ELISA.In addition,caspase-1 expression in lung tissues was quantified using qRT-PCR,and NF-κB and IL-6 expressions were assessed using immunohistochemistry.Results:The hWJMSCs decreased TNF-αlevels in the lung and plasma IL-18 and IL-1βlevels.Moreover,the hWJMSCs downregulated the expressions of caspase-1,IL-6,and NF-κB in lung tissues.Conclusions:The hWJMSCs can decrease inflammatory markers of acute respiratory distress syndrome in a rat model and may be further investigated for the treatment of acute respiratory distress syndrome.

Study on the Production Technology of Pueraria lobata Jelly

An orthogonal experiment was carried out to investigate the optimal production formula of Pueraria lobata jelly combining P. lobata,red beans and sugar as the main raw materials. The isoflavone contents in P. lobata and the P. lobata jelly were determined by colorimetry and sensory evaluation. The results showed that the optimal formula for the product was: P. lobata paste 50%,red bean paste 60%,and white granular sugar and agar 20% and 3% of the total weight of P. lobata paste and bean paste,respectively. The development of this product is of great significance to the utilization of P. lobata.

Formulation and evaluation of semisolid jelly produced by Musa acuminata Colla(AAA Group) peels

Objective:To study the jelly formulation produced by Musa acuminata Colla(AAA Group) peels and evaluate its antioxidant properties which are related to the product quality.Methods:The formulations of peel jelly were established under two-level full factorial designs within two blocks and one center point.Regarding response optimizer,the amount of sugar and citric acid was obtained;hence,the peel jellies were produced.The evaluation of antioxidant properties was conducted by using total phenolic content(TPC)assay and 1,1 diphenyl-2-picrylhydrazyl(DPPH) free radical assay.Results:The TPC of peel powder varied from 91.8 to 602.26 mg gallic acid equivalents/100 g dry weight,and 5%-7% peel jellies had phenolic content ranging from 29.38 to 48.31 mg gallic acid equivalents/100 g dry weight.The results of DPPH test indicated that at 10 mg/mL,the peel powder showed 89% DPPH inhibition,while 7% peel jelly prominently exhibited 84% DPPH inhibition.The correlation between DPPH IC50 value and TPC of peel powder as well as peel jelly was quite reasonably high with correlation coefficient ranging from 0.843 7 to 0.995.Conclusions:TPC can be used as an indicator in assessing the antioxidant activity of fruits and vegetables.The present investigation reveals that TPC is mainly responsible for DPPH free radical scavenging capacity.

Use of hybrid chitosan membranes and human mesenchymal stem cells from the Wharton jelly of umbilical cord for promoting nerve regeneration in an axonotmesis rat model

Many studies have been dedicated to the development of scaffolds for improving post-traumatic nerve regeneration. The goal of this study was to assess the effect on nerve regeneration, associating a hybrid chitosan membrane with non-differentiated human mesenchymal stem cells isolated from Wharton＇s jelly of umbilical cord, in peripheral nerve reconstruction after crush injury. Chromosome analysis on human mesenchymal stem cell line from Wharton＇s jelly was carried out and no structural alterations were found in metaphase. Chitosan membranes were previously tested in vitro, to assess their ability in supporting human mesenchymal stem cell survival, expansion, and differentiation. For the in vivo testing, Sasco Sprague adult rats were divided in 4 groups of 6 or 7 animals each： Group 1, sciatic axonotmesis injury without any other intervention （Group 1-Crush）; Group 2, the axonotmesis lesion of 3 mm was infiltrated with a suspension of 1 250 -1 500 human mesenchymal stem cells （total volume of 50 pL） （Group 2-CrushCell）; Group 3, axonotmesis lesion of 3 mm was enwrapped with a chitosan type Ill membrane covered with a monolayer of non-differentiated human mesenchymal stem cells （Group 3-CrushChitlllCell） and Group 4, axonotmesis lesion of 3 mm was enwrapped with a chitosan type III membrane （Group 4-CrushChiUll）. Motor and sensory functional recovery was evaluated throughout a healing period of 12 weeks using sciatic functional index, static sciatic index, extensor postural thrust, and withdrawal reflex latency. Stereological analysis was carded out on regenerated nerve fibers. Results showed that infiltration of human mesenchymal stem cells, or the combination of chitosan membrane enwrapment and human mesenchymal stem cell enrichment after nerve crush injury provide a slight advantage to post-traumatic nerve regeneration. Results obtained with chitosan type III membrane alone confirmed that they significantly improve post-traumatic axonal regrowth and may represent a very promising clinical tool in peripheral nerve reconstructive surgery. Yet, umbilical cord human mesenchymal stem cells, that can be expanded in culture and induced to form several different types of cells, may prove, in future experiments, to be a new source of cells for cell therapy, including targets such as peripheral nerve and muscle.