Differentiation of fetal pancreatic stem cells into neuron-like and islet-like cells in vitro

Pancreatic stem cells were isolated and cultured from aborted human fetal pancreases of gestational age 14-20 weeks. They were seeded at a density of 1 × 104 in serum-free media for differentiation into neuron-like cells, expressing β-tubulin III and glial fibrillary acidic protein. These neuron-like cells displayed a synapse-like morphology and appeared to form a neuronal network. Pancreatic stem cells were also seeded at a density of 1 × 105 for differentiation into islet-like cells, expressing insulin and glucagon, with an islet-like morphology. These cells had glucose-stimulated secretion of human insulin and C-peptide. Results suggest that pancreatic stem cells can be differentiated into neuron-like and islet-like cells.

Effects of human umbilical cord serum on proliferation and insulin content of human fetal islet-like cell clusters

BACKGROUND: Type 1 diabets is an autoimmune disease caused by the destruction of pancreatic β-cell with an in- creased incidence worldwide in the closing decades of the 20th century. This study was to investigate the effects of human umbilical cord serum (UCS) on the proliferation and function of human fetal islet-like cell clusters (ICCs) in vitro. METHODS: Eight fresh pancreatic glands obtained after in- duction of labor with water bag were mildly exposed to col- lagenase V, and the digested cells were cultured in a RPMI- 1640 medium plus 10% pooled UCS or fetal calf serum (FCS) to permit cells attachment and outgrowth of ICCs. RESULTS: In 8 consecutively explanted glands, develop- ment and proliferation of ICCs were observed. In the pre- sence of FCS, the outgrowth of ICC took place on the top of a flbroblast monocellular layer. UCS affected less growth of fibroblasts and increased the formation of ICCs about four-fold compared with explants from the same glands maintained in FCS. In both UCS and FCS, the insulin con- tent of the medium was variable to a certain extent and progressively declined from day 2 to day 6. Dithizone- stained ICCs in UCS suggested that most cell clusters were islet cells ( β-cells), and the purity of islets was estimated 80%-90%. The ultrastructure of the cultured cells showed a large number of granule-containing cells, most of which were identified as β-cells. CONCLUSION: We conclude that in comparison with ex- plants with FCS, the yield of ICCs and purification of islet cells are markedly increased by UCS and may facilitate the proliferation of pancreatic β-cells intended for islet trans- plantation.

Reversal of hyperglycemia in diabetic rats by portal vein transplantation of islet-like cells generated from bone marrow mesenchymal stem cells

AIM: To study the capacity of bone marrow mesenchymal stem cells (BM-MSCs) trans-differentiating into islet-like cells and to observe the effect of portal vein transplantation of islet-like cells in the treatment of streptozotocin-induced diabetic rat. METHODS: BM-MSCs were isolated from SD rats and induced to differentiate into islet-like cells under defined conditions. Differentiation was evaluated with electron microscopy, RT-PCR, immunofluorescence and flow cytometry. insulin release after glucose challenge was tested with ELiSA. Then allogeneic islet-like cells were transplanted into diabetic rats via portal vein. Blood glucose levels were monitored and islet hormones were detected in the liver and pancreas of the recipient by immunohistochemistry. RESULTS: BM-MSCs were spheroid adherent monolayers with high CD90, CD29 and very low CD45 expression. Typical islet-like cells clusters were formed after induction. Electron microscopy revealed that secretory granules were densely packed within the cytoplasm of the differentiated cells. The spheroid cells expressed islet related genes and hormones. The insulin-positive cells accounted for 19.8% and mean fluorescence intensity increased by 2.6 fold after induction. The cells secreted a small amount of insulin that was increased 1.5 fold after glucose challenge. After transplantation, islet-like cells could locate in the liver expressing islet hormones and lower the glucose levels of diabetic rats during d 6 to d 20.CONCLUSION: Rat BM-MSCs could be transdifferentiated into islet-like cells in vitro . Portal vein transplantation of islet-like cells could alleviate the hyperglycemia of diabetic rats.

眼斑双锯鱼(Amphiprion ocellaris)发育中体色花纹时序发生的色素细胞变化和控制基因表达的分析Ⅱ.仔稚幼鱼时期

眼斑双锯鱼(Amphiprion ocellaris)属于鲈形目、雀鲷科、双锯鱼属,是热带珊瑚礁观赏鱼类的首选品种,其不同发育时期各种色素细胞的动态变化及其控制基因表达情况有待深入研究。记录了眼斑双锯鱼仔稚幼鱼体色花纹模式建成的发育过程,对比不同发育时期体色变化的特点,筛选出仔稚幼鱼时期体色花纹变化较为明显的9个发育时期,并利用荧光定量PCR检测了眼斑双锯鱼各发育时期的10个体色控制基因的表达情况。结果显示:眼斑双锯鱼的体色发生存在明显的时序性,仔鱼时期鱼体呈现半透明状,黑色素细胞排列在身体两侧,随着生长发育数量逐渐增多;稚鱼时期,体表开始出现红色素细胞和黄色素细胞,身体慢慢变得不透明,9 dph开始出现第一道条纹,虹彩色素细胞数量逐渐增多,10 dph时期观察到第二道条纹出现;幼鱼时期,三道白色条纹完全形成,体表的橙红色和白色条纹被黑色素细胞分隔开来,界线逐渐清晰,长成完整的花纹。结合荧光定量PCR结果分析发现:在仔稚幼鱼阶段,10个体色控制基因在各发育时期均有表达,不同功能分类的基因在不同发育时期的表达变化趋势差异较大,在仔稚幼鱼前期表达量变化较大的基因主要为TYR、Dct、Ednrb、Sox10等与黑色素细胞迁移、分化、合成相关的基因;随着幼鱼不断的生长发育,白色条纹逐条出现,与虹彩色素细胞相关的Fms、Foxd3等基因也开始出现表达量显著上升的趋势。

Expression of Pdx-1 in bone marrow mesenchymal stem cells promotes differentiation of islet-like cells in vitro

Bone marrow mesenchymal stem cells(BMSCs) have the ability of self-renewal and multi-directional differentiation.Recent reports showed that BMSCs could differentiate into endocrine cells of pancreas.However,the differentiation is not efficient enough to produce insulin-producing cells for the future therapeutic use.Pdx-1 is a crucial regulator for pancreatic development.Therefore we constructed a eukaryotic expression vector containing Pdx-1 to determine the effect of Pdx-1 ex-pression on differentiation of BMSCs in vitro.The results showed that BMSCs could self-assemble to form functional pancreatic islet-like structures after differentiation in vitro.The proportion of insu-lin-producing cells differentiated from Pdx-1+BMSCs was 28.23%±2.56%,higher than that from BMSCs transfected with vacant vector and Pdx-1-BMSCs(7.23%±1.56% and 4.08%±2.69% respec-tively) by flow cytometry.Immunocytochemical examination also testified the expression of multiple β-cells-specific genes such as insulin,glucagons,somatostatin in differentiated BMSCs.The results also revealed that the expressions of genes mentioned above in Pdx-1+BMSCs were higher than that in Pdx-1-BMSCs,which was confirmed by Western blotting analysis and RT-PCR.Glucose-induced insulin secretion from Pdx-1+BMSCs in 5mmol/L and 25mmol/L glocuse was(56.61±4.82) μU/mL and(115.29±2.56) μU/mL respectively,which were much higher than those from Pdx-1-BMSCs((25.53±6.49) μU/mL and(53.26±7.56) μU/mL respectively) .Grafted animals were able to maintain their body weight and survive for relatively longer periods of time than hyperglycemic sham-grafted controls,which demonstrated an overall beneficial effect of the grafted cells on the health of the animals.These findings thus suggested that exogenous expression of Pdx-1 should provide a promising approach for efficiently producing islet-like cells from BMSCs for the future therapeutic use in diabetic patients.

Metabolic and proteostatic differences in quiescent and active neural stem cells

Adult neural stem cells are neurogenesis progenitor cells that play an important role in neurogenesis.Therefore,neural regeneration may be a promising target for treatment of many neurological illnesses.The regenerative capacity of adult neural stem cells can be chara cterized by two states:quiescent and active.Quiescent adult neural stem cells are more stable and guarantee the quantity and quality of the adult neural stem cell pool.Active adult neural stem cells are chara cterized by rapid proliferation and differentiation into neurons which allow for integration into neural circuits.This review focuses on diffe rences between quiescent and active adult neural stem cells in nutrition metabolism and protein homeostasis.Furthermore,we discuss the physiological significance and underlying advantages of these diffe rences.Due to the limited number of adult neural stem cells studies,we refe rred to studies of embryonic adult neural stem cells or non-mammalian adult neural stem cells to evaluate specific mechanisms.

Differentiation of marrow-derived islet-like cells and their effects on diabetic rats

In recent years, islet transplantation for diabetes has shown signs of the treatment efficacy, but its application is limited due to lack of donor organizations, sources and immune rejection. Bone marrow mesenchymal stem cells （BMSCs） have become a new resource of islet cell substitutes. One focus of the current research is the application of a specific inducing agent or a culture system to get directed differentiation of BMSCs, which may have part characteristics of islet cells and then be used in autologous transplantation for the treatment of diabetes.

The MORC2 p.S87L mutation reduces proliferation of pluripotent stem cells derived from a patient with the spinal muscular atrophy-like phenotype by inhibiting proliferation-related signaling pathways

Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical phenotype.The aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment strategies.Epithelial cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor cells.Next-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem cells.Reduced proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like patient.MORC2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem cells.Howeve r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor cells.These findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stage of pluripotent stem cell induction.

Evaluation of the intracellular lipid-lowering effect of polyphenols extract from highland barley in HepG2 cells

Active ingredients from highland barley have received considerable attention as natural products for developing treatments and dietary supplements against obesity.In practical application,the research of food combinations is more significant than a specific food component.This study investigated the lipid-lowering effect of highland barley polyphenols via lipase assay in vitro and HepG2 cells induced by oleic acid(OA).Five indexes,triglyceride(TG),total cholesterol(T-CHO),low density lipoprotein-cholesterol(LDL-C),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),were used to evaluate the lipidlowering effect of highland barley extract.We also preliminary studied the lipid-lowering mechanism by Realtime fluorescent quantitative polymerase chain reaction(q PCR).The results indicated that highland barley extract contains many components with lipid-lowering effects,such as hyperoside and scoparone.In vitro,the lipase assay showed an 18.4%lipase inhibition rate when the additive contents of highland barley extract were 100μg/m L.The intracellular lipid-lowering effect of highland barley extract was examined using 0.25 mmol/L OA-induced HepG2 cells.The results showed that intracellular TG,LDL-C,and T-CHO content decreased by 34.4%,51.2%,and 18.4%,respectively.ALT and AST decreased by 51.6%and 20.7%compared with the untreated hyperlipidemic HepG2 cells.q PCR results showed that highland barley polyphenols could up-regulation the expression of lipid metabolism-related genes such as PPARγand Fabp4.

Cell metabolism pathways involved in the pathophysiological changes of diabetic peripheral neuropathy

Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.

Model reduction of fractional impedance spectra for time–frequency analysis of batteries, fuel cells, and supercapacitors

Joint time–frequency analysis is an emerging method for interpreting the underlying physics in fuel cells,batteries,and supercapacitors.To increase the reliability of time–frequency analysis,a theoretical correlation between frequency-domain stationary analysis and time-domain transient analysis is urgently required.The present work formularizes a thorough model reduction of fractional impedance spectra for electrochemical energy devices involving not only the model reduction from fractional-order models to integer-order models and from high-to low-order RC circuits but also insight into the evolution of the characteristic time constants during the whole reduction process.The following work has been carried out:(i)the model-reduction theory is addressed for typical Warburg elements and RC circuits based on the continued fraction expansion theory and the response error minimization technique,respectively;(ii)the order effect on the model reduction of typical Warburg elements is quantitatively evaluated by time–frequency analysis;(iii)the results of time–frequency analysis are confirmed to be useful to determine the reduction order in terms of the kinetic information needed to be captured;and(iv)the results of time–frequency analysis are validated for the model reduction of fractional impedance spectra for lithium-ion batteries,supercapacitors,and solid oxide fuel cells.In turn,the numerical validation has demonstrated the powerful function of the joint time–frequency analysis.The thorough model reduction of fractional impedance spectra addressed in the present work not only clarifies the relationship between time-domain transient analysis and frequency-domain stationary analysis but also enhances the reliability of the joint time–frequency analysis for electrochemical energy devices.

Cell replacement with stem cell-derived retinal ganglion cells from different protocols

Glaucoma,characterized by a degenerative loss of retinal ganglion cells,is the second leading cause of blindness worldwide.There is currently no cure for vision loss in glaucoma because retinal ganglion cells do not regenerate and are not replaced after injury.Human stem cell-derived retinal ganglion cell transplant is a potential therapeutic strategy for retinal ganglion cell degenerative diseases.In this review,we first discuss a 2D protocol for retinal ganglion cell differentiation from human stem cell culture,including a rapid protocol that can generate retinal ganglion cells in less than two weeks and focus on their transplantation outcomes.Next,we discuss using 3D retinal organoids for retinal ganglion cell transplantation,comparing cell suspensions and clusters.This review provides insight into current knowledge on human stem cell-derived retinal ganglion cell differentiation and transplantation,with an impact on the field of regenerative medicine and especially retinal ganglion cell degenerative diseases such as glaucoma and other optic neuropathies.

Erastin-induced ferroptosis is a regulator forthe growth and function of humanpancreatic islet-like cell clusters

Ferroptosis is a newly identified and novel form of cell death, which is characterized by an iron- and reactiveoxygen species (ROS)-dependent manner. Potential utility of ferroptotic cell death has been recently proposed forcancer treatment. Meanwhile, ROS generation and apoptosis are inherently consequent to cell apoptosis anddysfunction during islet cell preparation and transplantation. Whether ferroptosis induction is a regulator for cellviability and function in human pancreatic islet-cell clusters (ICCs) derived from pancreatic progenitor cells (PPCs)remains elusive. We thus sought to induce ferroptosis in our established cell culture system of human PPCs/ICCs,examine the effects of ferroptosis on ICCs, and explore the potential regulatory pathways involved. Our resultsshowed that ICCs were prone to the use of ferroptosis-inducing and inhibiting agents under our culture conditions.Erastin, a ferroptosis inducer, was found to trigger ferroptosis in ICCs, without the apparent detection of other typesof cell death involved, such as apoptosis and autophagy. In corroboration, the use of ferroptosis inhibitor,ferrostatin-1 (Fer-1), was found to enhance the cell viability of ICCs and prevent them from ferroptosis as well asimprove its function. Mechanistically, the erastin-induced ferroptosis in ICCs was probably mediated via activation ofJNK/P38/MAPK pathways and upregulation of NOX4 expression. Together, our findings may provide a scientificbasis of ferroptosis inhibition as a potential for the amelioration of ICC survival and functionality during islettransplantation in diabetic patients.

The combined application of stem cells and three-dimensional bioprinting scaffolds for the repair of spinal cord injury

Spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous system.Following surgery,the poor regenerative capacity of nerve cells and the generation of new scars can make it very difficult for the impaired nervous system to restore its neural functionality.Traditional treatments can only alleviate secondary injuries but cannot fundamentally repair the spinal cord.Consequently,there is a critical need to develop new treatments to promote functional repair after spinal cord injury.Over recent years,there have been seve ral developments in the use of stem cell therapy for the treatment of spinal cord injury.Alongside significant developments in the field of tissue engineering,three-dimensional bioprinting technology has become a hot research topic due to its ability to accurately print complex structures.This led to the loading of three-dimensional bioprinting scaffolds which provided precise cell localization.These three-dimensional bioprinting scaffolds co uld repair damaged neural circuits and had the potential to repair the damaged spinal cord.In this review,we discuss the mechanisms underlying simple stem cell therapy,the application of different types of stem cells for the treatment of spinal cord injury,and the different manufa cturing methods for three-dimensional bioprinting scaffolds.In particular,we focus on the development of three-dimensional bioprinting scaffolds for the treatment of spinal cord injury.

TM9SF1 promotes bladder cancer cell growth and infiltration

BACKGROUND Bladder cancer(BC)is the most common urological tumor.It has a high recur-rence rate,displays tutor heterogeneity,and resists chemotherapy.Furthermore,the long-term survival rate of BC patients has remained unchanged for decades,which seriously affects the quality of patient survival.To improve the survival rate and prognosis of BC patients,it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention.Transmembrane 9 superfamily member 1(TM9SF1),also known as MP70 and HMP70,is a member of a family of nine transmembrane superfamily proteins,which was first identified in 1997.TM9SF1 can be expressed in BC,but its biological function and mechanism in BC are not clear.AIM To investigate the biological function and mechanism of TM9SF1 in BC.Overexpression of TM9SF1 increased the in vitro proliferation,migration,and invasion of BC cells by promoting the entry of BC cells into the G2/M phase.Silencing of TM9SF1 inhibited in vitro proliferation,migration,and invasion of BC cells and blocked BC cells in the G1 phase.CONCLUSION TM9SF1 may be an oncogene in BC.

Long non-coding RNA H19 regulates neurogenesis of induced neural stem cells in a mouse model of closed head injury

Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.

Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.

Promoting Sickle Cell Trait Awareness and Education: A Typology of Interventions in the United States to Inform Ongoing Efforts to Patients and Providers

Research Background: Sickle cell trait has no treatment or cure and predominantly affects people who are Black, but can affect anyone of any race or ethnicity. While commonly incorrectly considered benign by providers and the public, people with a sickle cell trait experience life-threatening outcomes that are exacerbated by extreme conditions. There is a severe lack of awareness and understanding of sickle cell trait and the associated health complications among sickle cell trait carriers and healthcare providers. Purpose/Aim: Interventions that aim to improve awareness of sickle cell trait differ in approaches and are not well documented in the literature. This typology aims to highlight current efforts to inform targeted interventions that raise awareness through consistent messaging, educate people and providers on sickle cell trait and the related health complications, and support the design and implementation of comprehensive sickle cell trait awareness initiatives. Methods: We conducted a scoping review of United States-based sickle cell trait interventions and performed a content analysis to identify the categories and characteristics of these efforts. We then organized the results into a typology according to established protocols. Results: Among 164 interventions, twenty-five (15%) met the typology inclusion criteria described above and were grouped into categories: Seven of twenty-five interventions were Educational Interventions (28%), three of twenty-five interventions (12%) were Combined Screening and Educational-Based Interventions, eight of twenty-five interventions (32%) were Policy and Guideline-Based Intervention, and six of twenty-five interventions (24%) were Sickle Cell Trait Organization-Led Interventions. Conclusions: There is a lack of consistency in messaging across interventions whether delivered by credible healthcare institutions or national organizations, which can result in lack of education and awareness and confusion around sickle cell trait. Categorizing interventions through a typology allows clarity and informs consistency in messaging, which should be at the forefront of future sickle cell trait efforts.

High glucose microenvironment and human mesenchymal stem cell behavior

High glucose(HG)culture conditions in vitro and persistent exposure to hyperglycemia in diabetes patients are detrimental to stem cells,analogous to any other cell type in our body.It interferes with diverse signaling pathways,i.e.mammalian target of rapamycin(mTOR)-phosphoinositide 3-kinase(PI3K)-Akt signaling,to impact physiological cellular functions,leading to low cell survival and higher cell apoptosis rates.While elucidating the underlying mechanism responsible for the apoptosis of adipose tissue-derived mesenchymal stem cells(MSCs),a recent study has shown that HG culture conditions dysregulate mTORPI3K-Akt signaling in addition to mitochondrial malfunctioning due to defective mitochondrial membrane potential(MtMP)that lowers ATP production.This organelle-level dysfunction energy-starves the cells and increases oxidative stress and ultrastructural abnormalities.Disruption of the mitochondrial electron transport chain produces an altered mitochondrial NAD+/NADH redox state as evidenced by a low NAD+/NADH ratio that primarily contributes to the reduced cell survival in HG.Some previous studies have also reported altered mitochondrial membrane polarity(causing hyperpolarization)and reduced mitochondrial cell mass,leading to perturbed mitochondrial homeostasis.The hostile microenvironment created by HG exposure creates structural and functional changes in the mitochondria,altering their bioenergetics and reducing their capacity to produce ATP.These are significant data,as MSCs are extensively studied for tissue regeneration and restoring their normal functioning in cell-based therapy.Therefore,MSCs from hyperglycemic donors should be cautiously used in clinical settings for cell-based therapy due to concerns of their poor sur-vival rates and increased rates of post engraftment proliferation.As hypergly-cemia alters the bioenergetics of donor MSCs,rectifying the loss of MtMP may be an excellent target for future research to restore the normal functioning of MSCs in hyperglycemic patients.

Emerging strategies for nerve repair and regeneration in ischemic stroke:neural stem cell therapy

Ischemic stroke is a major cause of mortality and disability worldwide,with limited treatment options available in clinical practice.The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function.Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect.Neural stem cells regulate multiple physiological responses,including nerve repair,endogenous regeneration,immune function,and blood-brain barrier permeability,through the secretion of bioactive substances,including extracellular vesicles/exosomes.However,due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation,limitations in the treatment effect remain unresolved.In this paper,we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke,review current neural stem cell therapeutic strategies and clinical trial results,and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells.We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.