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Biomaterial-assisted biotherapy:A brief review of biomaterials used in drug delivery,vaccine development,gene therapy,and Stem cell therapy

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Bioactive Materials 2022年第11期7卷 29-48页

作者： Xuejiao Han Aqu Alu Hongmei Liu Yi Shi Xiawei Wei Lulu Cai Yuquan Wei Laboratory of Aging Research and Cancer Drug Target State Key Laboratory of BiotherapyNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduChina Personalized Drug therapy Key Laboratory of Sichuan Province Department of PharmacySichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengdu610072China Sichuan Provincial Key Laboratory for Human Disease Gene Study and Department of Laboratory Medicine Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu610072China

Biotherapy has recently become a hotspot research topic with encouraging prospects in various fields due to a wide range of treatments applications,as demonstrated in preclinical and clinical studies.However,the broad applications of biotherapy have been limited by critical challenges,including the lack of safe and efficient de-livery systems and serious side effects.Due to the unique potentials of biomaterials,such as good biocompati-bility and bioactive properties,biomaterial-assisted biotherapy has been demonstrated to be an attractive strategy.The biomaterial-based delivery systems possess sufficient packaging capacity and versatile functions,enabling a sustained and localized release of drugs at the target sites.Furthermore,the biomaterials can provide a niche with specific extracellular conditions for the proliferation,differentiation,attachment,and migration of stem cells,leading to tissue regeneration.In this review,the state-of-the-art studies on the applications of bio-materials in biotherapy,including drug delivery,vaccine development,gene therapy,and Stem cell therapy,have been summarized.The challenges and an outlook of biomaterial-assisted biotherapies have also been discussed.

关键词： Biomaterial Biotherapy Drug delivery system Vaccine development Gene therapy Stem cell therapy

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Stem cell therapy for Alzheimer’s disease:An overview of experimental models and reality

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Animal Models and Experimental Medicine 2022年第1期5卷 15-26页

作者： Chuan Qin Kewei Wang Ling Zhang Lin Bai Institute of Laboratory Animal Sciences Chinese Academy of Medical Sciences(CAMS)Comparative Medicine CenterPeking Union Medical College(PUMC)NHC Key Laboratory of Human Disease Comparative MedicineKey Laboratory of Human Diseases Animal ModelBeijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases BeijingBeijingChina

Alzheimer's disease(AD)is a neurodegenerative disorder.The pathology of AD is characterized by extracellular amyloid beta(Aβ)plaques,neurofibrillary tangles com-posed of hyperphosphorylated tau,neuronal death,synapse loss,and brain atrophy.Many therapies have been tested to improve or at least effectively modify the course of AD.Meaningful data indicate that the transplantation of stem cells can alleviate neuropathology and significantly ameliorate cognitive deficits in animal models with Alzheimer's disease.Transplanted stem cells have shown their inherent advantages in improving cognitive impairment and memory dysfunction,although certain weak-nesses or limitations need to be overcome.This review recapitulates rodent models for AD,the therapeutic efficacy of stem cells,influencing factors,and the underlying mechanisms behind these changes.Stem cell therapy provides perspective and chal-lenges for its clinical application in the future.

关键词： Alzheimer's disease animal model cognitive deficits memory loss Stem cell therapy

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Treatment of spinal cord injury with biomaterials and Stem cell therapy in non-human primates and humans

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Neural Regeneration Research 2025年第2期20卷 343-353页

作者： Ana Milena Silva Olaya Fernanda Martins Almeida Ana Maria Blanco Martinez Suelen Adriani Marques PhD Program in Pathological Anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Biomedical Science Institute Federal University of Rio de JaneiroRio de JaneiroBrazil Graduate Program in Pathological Anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Graduate Program in Pathological Anatomy(PPGAP/UFRJ) Department of Neurobiology/Institute of BiologyCampus do GragoatáNiteróiRio de JaneiroBrazil

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and Stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

关键词： bioengineering biomaterials cell therapy humans non-human primates spinal cord injury Stem cell therapy

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Effectiveness and mechanisms of adiposederived Stem cell therapy in animal models of Parkinson’s disease:a systematic review and meta-analysis

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Translational Neurodegeneration 2021年第2期10卷 166-177页

作者： Keya Li Xinyue Li Guiying Shi Xuepei Lei Yiying Huang Lin Bai Chuan Qin NHC Key Laboratory of Human Disease Comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijing 100021China

Animal models provide an opportunity to assess the optimal treatment way and the underlying mechanisms of direct clinical application of adipose-derived stem cells(ADSCs).Previous studies have evaluated the effects of primitive and induced ADSCs in animal models of Parkinson’s disease(PD).Here,eight databases were systematically searched for studies on the effects and in vivo changes caused by ADSC intervention.Quality assessment was conducted using a 10-item risk of bias tool.For the subsequent meta-analysis,study characteristics were extracted and effect sizes were computed.Ten out of 2324 published articles(n=169 animals)were selected for further meta-analysis.After ADSC therapy,the rotation behavior(10 experiments,n=156 animals)and rotarod performance(3 experiments,n=54 animals)were improved(Pcells(−2.18;95%CI,−3.29 to−1.07).Stratified analyses by different time intervals indicated that ADSC intervention exhibited a long-term effect.Following the transplantation of ADSCs,tyrosine hydroxylase-positive neurons recovered in the lesion area with pooled SMD of 13.36[6.85,19.86].Transplantation of ADSCs is a therapeutic option that shows long-lasting effects in animal models of PD.The potential mechanisms of ADSCs involve neurogenesis and neuroprotective effects.The standardized induction of neural form of transplanted ADSCs can lead to a future application in clinical practice.

关键词： Parkinson’s disease Adipose-derived stem cells Animal model Stem cell therapy Meta-analysis Neurogenesis Neuroprotection

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Pursuing meaningful end-points for Stem cell therapy assessment in ischemic cardiac disease

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World Journal of stem cells 2017年第12期9卷 203-218页

作者： Maria Dorobantu Nicoleta-Monica Popa-Fotea Mihaela Popa Iulia Rusu Miruna Mihaela Micheu Department of Cardiology Clinical Emergency Hospital of Bucharest Carol Davila University of Medicine 'Carol Davila' University of Medicine and Pharmacy Bucharest

Despite optimal interventional and medical therapy, ischemic heart disease is still an important cause of morbidity and mortality worldwide. Although not included in standard of care rehabilitation, Stem cell therapy(SCT) could be a solution for prompting cardiac regeneration. Multiple studies have been published from the beginning of SCT until now, but overall no unanimous conclusion could be drawn in part due to the lack of appropriate endpoints. In order to appreciate the impact of SCT, multiple markers from different categories should be considered: Structural, biological, functional, physiological, but also major adverse cardiac events or quality of life. Imaging end-points are among the most used-especially left ventricle ejection fraction(LVEF) measured through different methods. Other imaging parameters are infarct size, myocardial viability and perfusion. The impact of SCT on all of the aforementioned end-points is controversial and debatable. 2 D-echocardiography is widely exploited, but new approaches such as tissue Doppler, strain/strain rate or 3 D-echocardiography are more accurate, especially since the latter one is comparable with the MRI gold standard estimation of LVEF. Apart from the objective parameters, there are also patient-centered evaluations to reveal the benefits of SCT, such as quality of life and performance status, the most valuable from the patient point of view. Emerging parameters investigating molecular pathways such as non-coding RNAs or inflammation cytokines have a high potential as prognostic factors. Due to the disadvantages of current techniques, new imaging methods with labelled cells tracked along their lifetime seem promising, but until now only pre-clinical trials have been conducted in humans. Overall, SCT is characterized by high heterogeneity not only in preparation, administration and type of cells, but also in quantification of therapy effects.

关键词： Stem cell therapy Cardiac imaging techniques Ischemic cardiac disease Cardiac regeneration Endpoints

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Stem cell therapy for central nerve system injuries: glial cells hold the key

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Neural Regeneration Research 2014年第13期9卷 1253-1260页

作者： Li Xiao Chikako Saiki Ryoji Ide Pharmacology Department The Nippon Dental University School of Life Dentistry at Tokyo Tokyo Japan Physiology Department The Nippon Dental University School of Life Dentistry at Tokyo Tokyo Japan

Mammalian adult central nerve system （CNS） injuries are devastating because of the intrinsic difficulties for effective neuronal regeneration. The greatest problem to be overcome for CNS recovery is the poor regeneration of neurons and myelin-forming cells, oligodendrocytes. Endogenous neural progenitors and transplanted exogenous neuronal stem cells can be the source for neuronal regeneration. However, because of the harsh local microenvironment, they usually have very low efficacy for functional neural regeneration which cannot compensate for the loss of neurons and oligodendrocytes. Glial cells （including astrocytes, microglia, oligodendrocytes and NG2 glia） are the majority of cells in CNS that provide support and protection for neurons. Inside the local microenvironment, glial cells largely influence local and transplanted neural stem cells survival and fates. This review critically analyzes current finding of the roles of glial cells in CNS regeneration, and highlights strategies for regulating glial cells＇ behavior to create a permissive microenvironment for neuronal stem cells.

关键词： Neuron regeneration Stem cell therapy glial cells microenvironment oligodendrocyteregeneration CNS injury

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stem cell-based ischemic stroke therapy:Novel modifications and clinical challenges

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Asian Journal of Pharmaceutical Sciences 2024年第1期19卷 18-34页

作者： Yuankai Sun Xinchi Jiang Jianqing Gao Institute of Pharmaceutics College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Hangzhou Institute of Innovative Medicine College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Dr.Li Dak Sum&Yip Yio Chin Center for stem cell and Regenerative Medicine Zhejiang UniversityHangzhou 310058China Department of Pharmacy The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China

Ischemic stroke(IS)causes severe disability and high mortality worldwide.stem cell(SC)therapy exhibits unique therapeutic potential for IS that differs from current treatments.SC’s cell homing,differentiation and paracrine abilities give hope for neuroprotection.Recent studies on SC modification have enhanced therapeutic effects for IS,including gene transfection,nanoparticle modification,biomaterial modification and pretreatment.Thesemethods improve survival rate,homing,neural differentiation,and paracrine abilities in ischemic areas.However,many problems must be resolved before SC therapy can be clinically applied.These issues include production quality and quantity,stability during transportation and storage,as well as usage regulations.Herein,we reviewed the brief pathogenesis of IS,the“multi-mechanism”advantages of SCs for treating IS,various SC modification methods,and SC therapy challenges.We aim to uncover the potential and overcome the challenges of using SCs for treating IS and convey innovative ideas for modifying SCs.

关键词： Ischemic stroke Stem cell therapy stem cell modification cell therapy challenge

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Quantification of corneal neovascularization after ex vivo limbal epithelial Stem cell therapy

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International Journal of Ophthalmology(English edition) 2014年第6期7卷 988-995页

作者： Adriano Guarnieri Javier Moreno-Monta?és Belén Alfonso-Bartolozzi Alfonso L.Sabater María García-Guzmán Enrique J.Andreu Felipe Prosper Department of Ophthalmology Clínica Universidad de Navarra Department of cell therapy Clínica Universidad de Navarra

AIM: To assess cultured limbal epithelial stem cell transplantation in patients with limbal stem cell deficiency by analyzing and quantifying corneal neovascularization.METHODS: This retrospective, interventional case series included eight eyes with total limbal stem cell deficiency. Ex vivo limbal epithelial stem cells were cultured on human amniotic membrane using an animalfree culture method. The clinical parameters of limbal stem cell deficiency, impression cytology, and quantification of corneal neovascularization were evaluated before and after cultured limbal stem cell transplantation. The area of corneal neovascularization,vessel caliber(VC), and invasive area(IA) were analyzed before and after stem cell transplantation by image analysis software. Best-corrected visual acuity(BCVA),epithelial transparency, and impression cytology were also measured.RESULTS: One year after surgery, successful cases showed a reduction(improvement) of all three parameters of corneal neovascularization [neovascular area(NA), VC, IA], while failed cases did not. NA decreased a mean of 32.31%(P =0.035), invasion area29.37%(P =0.018) and VC 14.29%(P =0.072). BCVA improved in all eyes(mean follow-up, 76 ±21mo).Epithelial transparency improved significantly from 2.00 ±0.93 to 0.88±1.25(P =0.014). Impression cytology showed that three cases failed after limbal epithelial Stem cell therapy before 1y of follow-up.CONCLUSION: This method of analyzing andmonitoring surface vessels is useful for evaluating the epithelial status during follow-up, as successful cases showed a bigger reduction in corneal neovascularization parameters than failed cases. Using this method,successful cases could be differentiated from failed cases.

关键词： limbal stem cell corneal neovascularization Stem cell therapy impression cytology limbal stem cell deficiency

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Pancreatic transplant surgery and Stem cell therapy:Finding the balance between therapeutic advances and ethical principles

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World Journal of stem cells 2022年第8期14卷 577-586页

作者： Martina Padovano Matteo Scopetti Federico Manetti Donato Morena Davide Radaelli Stefano D’Errico Nicola Di Fazio Paola Frati Vittorio Fineschi Department of Anatomical HistologicalForensic and Orthopaedic SciencesSapienza University of RomeRome 00185Italy Department of Medical Surgical Sciences and Translational Medicine Sapienza University of RomeRome 00189Italy Department of Medicine Surgery and HealthUniversity of TriesteTrieste 34149Italy

The latest achievements in the field of pancreas transplantation and Stem cell therapy require an effort by the scientific community to clarify the ethical implications of pioneering treatments,often characterized by high complexity from a surgical point of view,due to transplantation of multiple organs at the same time or at different times,and from an immunological point of view for Stem cell therapy.The fundamental value in the field of organ transplants is,of course,a solidarity principle,namely that of protecting the health and life of people for whom transplantation is a condition of functional recovery,or even of survival.The nature of this value is that of a concept to which the legal discipline of transplants entrusts its own ethical dignity and for which it has ensured a constitutional recognition in different systems.The general principle of respect for human life,both of the donor and of the recipient,evokes the need not to put oneself and one’s neighbor in dangerous conditions.The present ethical reflection aims to find a balance between the latest therapeutic advances and several concepts including the idea of the person,the respect due to the dead,the voluntary nature of the donation and the consent to the same,the gratuitousness of the donation,the scientific progress and the development of surgical techniques,and the policies of health promotion.

关键词： Pancreas transplantation Multi-organ transplants Stem cell therapy Ethical principles Donor Recipient

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Stem cell therapy for insulin-dependent diabetes:Are we still on the road?

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World Journal of stem cells 2022年第7期14卷 503-512页

作者： Lu Yang Zhu-Meng Hu Fang-Xu Jiang Wei Wang Department of Endocrinology Xiang’an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361100Fujian ProvinceChina School of Biomedical Science University of Western AustraliaNedlands 6009Australia School of Health and Medical Sciences Edith Cowan UniversityPerth 6000Australia

In insulin-dependent diabetes,the isletβcells do not produce enough insulin and the patients must receive exogenous insulin to control blood sugar.However,there are still many deficiencies in exogenous insulin supplementation.Therefore,the replacement of destroyed functionalβcells with insulin-secreting cells derived from functional stem cells is a good idea as a new therapeutic idea.This review introduces the development schedule of mouse and human embryonic islets.The differences between mouse and human pancreas embryo development were also listed.Accordingly to the different sources of stem cells,the important research achievements on the differentiation of insulin-secretingβcells of stem cells and the current research status of Stem cell therapy for diabetes were reviewed.stem cell replacement therapy is a promising treatment for diabetes,caused by defective insulin secretion,but there are still many problems to be solved,such as the biosafety and reliability of treatment,the emergence of tumors during treatment,untargeted differentiation and autoimmunity,etc.Therefore,further understanding of Stem cell therapy for insulin is needed.

关键词： Diabetes mellitus Stem cell therapy Transplantation βcell Differentiation

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