|
1
|
Kushwaha V, Sahu KK. A Comprehensive Review on Preclinical Alzheimer's Disease Models: Evaluating their Clinical Relevance. Curr Pharm Biotechnol 2025; 26:186-207. [PMID: 39161136 DOI: 10.2174/0113892010331845240802073645] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 06/15/2024] [Accepted: 07/02/2024] [Indexed: 08/21/2024]
Abstract
Alzheimer's disease (AD) is a neurological disorder that increases with age and must be treated immediately by worldwide healthcare systems. Internal neurofibrillary tau tangles and extracellular amyloid accumulation have been widely recognized as the primary causes of Alzheimer's disease. These degenerative age-related ailments are expected to proliferate exponentially as life expectancy rises. Experimental models of AD are essential for acquiring a deep knowledge of its pathogenesis and determining the viability of novel therapy options. Although there isn't a model that encompasses all the characteristics of real AD, these models are nonetheless highly helpful for the research of various modifications associated with it, even though they are only partially indicative of the disease circumstances being studied. Better knowledge of the advantages and disadvantages of each of the different models, as well as the use of more than one model to evaluate potential medications, would increase the effectiveness of therapy translation from preclinical research to patients. We outline the pathogenic characteristics and limitations of the main experimental models of AD in this review, including transgenic mice, transgenic rats, primates and non-primate models along with in-vitro cell culture models in humans. Additionally, it highlights the possible future of experimental modeling of AD and includes the co-morbid models.
Collapse
Affiliation(s)
- Virendra Kushwaha
- Institute of Pharmaceutical Research, GLA University, Mathura, UP, 281406, India
| | - Kantrol Kumar Sahu
- Institute of Pharmaceutical Research, GLA University, Mathura, UP, 281406, India
| |
Collapse
|
|
2
|
Zhang Y, Chen J, Li Y, Jiao B, Luo S. Disease-modifying therapies for Alzheimer's disease: Clinical trial progress and opportunity. Ageing Res Rev 2025; 103:102595. [PMID: 39581354 DOI: 10.1016/j.arr.2024.102595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 11/19/2024] [Accepted: 11/19/2024] [Indexed: 11/26/2024]
Abstract
The U.S. Food and Drug Administration (FDA) recently approved lecanemab and donanemab for the treatment of early symptomatic Alzheimer's disease (AD) after their phase III trials reached endpoints. These two anti-amyloid β monoclonal antibodies represent the latest promise of disease-modifying therapy (DMT) for AD, which undoubtedly reignites new hope for DMTs to combat the staggering financial and human costs of AD. However, in addition to these two successful antibodies, there have been enormous efforts to develop DMTs in various aspects to meet the therapeutic requirement of AD. In this review, we delineate the core principles and methodologies of diverse DMTs, covering the advances in clinical trials of drug candidates that either have been discontinued, completed, or are ongoing, as well as brain stimulation and lifestyle interventions. In addition, by overseeing the fate of various candidate molecules, we hope to provide references and ideas for prospective approaches and promising applications of DTMs for AD, particularly in terms of universality and clinical application economics, to optimize efficacy and maximize AD patient benefits in the future.
Collapse
Affiliation(s)
- Yujie Zhang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, PR China; Xiangya School of Medicine, Central South University, Changsha 410013, PR China
| | - Jie Chen
- Department of Rehabilitation, Xiangya Boai Rehabilitation Hospital, Changsha 410100, PR China
| | - Yanru Li
- Department of Rehabilitation, Xiangya Boai Rehabilitation Hospital, Changsha 410100, PR China
| | - Bin Jiao
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, PR China; National Clinical Research Center for Geriatric Disorders, Central South University, Changsha 410008, PR China; Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha 410000, PR China; Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha 410008, PR China
| | - Shilin Luo
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, PR China; National Clinical Research Center for Geriatric Disorders, Central South University, Changsha 410008, PR China; Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha 410000, PR China; Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha 410008, PR China.
| |
Collapse
|
|
3
|
Kumar R, Mahajan S, Gupta U, Madan J, Godugu C, Guru SK, Singh PK, Parvatikar P, Maji I. Stem cell therapy as a novel concept to combat CNS disorders. TARGETED THERAPY FOR THE CENTRAL NERVOUS SYSTEM 2025:175-206. [DOI: 10.1016/b978-0-443-23841-3.00009-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
4
|
Belousova E, Salikhova D, Maksimov Y, Nebogatikov V, Sudina A, Goldshtein D, Ustyugov A. Proposed Mechanisms of Cell Therapy for Alzheimer's Disease. Int J Mol Sci 2024; 25:12378. [PMID: 39596443 PMCID: PMC11595163 DOI: 10.3390/ijms252212378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Revised: 11/08/2024] [Accepted: 11/12/2024] [Indexed: 11/28/2024] Open
Abstract
Alzheimer's disease is a progressive neurodegenerative disorder characterized by mitochondria dysfunction, accumulation of beta-amyloid plaques, and hyperphosphorylated tau tangles in the brain leading to memory loss and cognitive deficits. There is currently no cure for this condition, but the potential of stem cells for the therapy of neurodegenerative pathologies is actively being researched. This review discusses preclinical and clinical studies that have used mouse models and human patients to investigate the use of novel types of stem cell treatment approaches. The findings provide valuable insights into the applications of stem cell-based therapies and include the use of neural, glial, mesenchymal, embryonic, and induced pluripotent stem cells. We cover current studies on stem cell replacement therapy where cells can functionally integrate into neural networks, replace damaged neurons, and strengthen impaired synaptic circuits in the brain. We address the paracrine action of stem cells acting via secreted factors to induce neuroregeneration and modify inflammatory responses. We focus on the neuroprotective functions of exosomes as well as their neurogenic and synaptogenic effects. We look into the shuttling of mitochondria through tunneling nanotubes that enables the transfer of healthy mitochondria by restoring the normal functioning of damaged cells, improving their metabolism, and reducing the level of apoptosis.
Collapse
Affiliation(s)
- Ekaterina Belousova
- Research Centre for Medical Genetics, Moscow 115522, Russia; (E.B.); (D.S.); (Y.M.); (A.S.); (D.G.)
| | - Diana Salikhova
- Research Centre for Medical Genetics, Moscow 115522, Russia; (E.B.); (D.S.); (Y.M.); (A.S.); (D.G.)
- Research Institute of Molecular and Cellular Medicine of the Medical Institute Peoples’ Friendship, University of Russia, Moscow 117198, Russia
| | - Yaroslav Maksimov
- Research Centre for Medical Genetics, Moscow 115522, Russia; (E.B.); (D.S.); (Y.M.); (A.S.); (D.G.)
- Research Institute of Molecular and Cellular Medicine of the Medical Institute Peoples’ Friendship, University of Russia, Moscow 117198, Russia
| | - Vladimir Nebogatikov
- Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry of the Russian Academy of Sciences, Chernogolovka 142432, Russia;
| | - Anastasiya Sudina
- Research Centre for Medical Genetics, Moscow 115522, Russia; (E.B.); (D.S.); (Y.M.); (A.S.); (D.G.)
- Research Institute of Molecular and Cellular Medicine of the Medical Institute Peoples’ Friendship, University of Russia, Moscow 117198, Russia
| | - Dmitry Goldshtein
- Research Centre for Medical Genetics, Moscow 115522, Russia; (E.B.); (D.S.); (Y.M.); (A.S.); (D.G.)
| | - Aleksey Ustyugov
- Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry of the Russian Academy of Sciences, Chernogolovka 142432, Russia;
| |
Collapse
|
|
5
|
Yang L, Liu SC, Liu YY, Zhu FQ, Xiong MJ, Hu DX, Zhang WJ. Therapeutic role of neural stem cells in neurological diseases. Front Bioeng Biotechnol 2024; 12:1329712. [PMID: 38515621 PMCID: PMC10955145 DOI: 10.3389/fbioe.2024.1329712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 02/12/2024] [Indexed: 03/23/2024] Open
Abstract
The failure of endogenous repair is the main feature of neurological diseases that cannot recover the damaged tissue and the resulting dysfunction. Currently, the range of treatment options for neurological diseases is limited, and the approved drugs are used to treat neurological diseases, but the therapeutic effect is still not ideal. In recent years, different studies have revealed that neural stem cells (NSCs) have made exciting achievements in the treatment of neurological diseases. NSCs have the potential of self-renewal and differentiation, which shows great foreground as the replacement therapy of endogenous cells in neurological diseases, which broadens a new way of cell therapy. The biological functions of NSCs in the repair of nerve injury include neuroprotection, promoting axonal regeneration and remyelination, secretion of neurotrophic factors, immune regulation, and improve the inflammatory microenvironment of nerve injury. All these reveal that NSCs play an important role in improving the progression of neurological diseases. Therefore, it is of great significance to better understand the functional role of NSCs in the treatment of neurological diseases. In view of this, we comprehensively discussed the application and value of NSCs in neurological diseases as well as the existing problems and challenges.
Collapse
Affiliation(s)
- Ling Yang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China
- Department of Physical Examination, The Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China
| | - Si-Cheng Liu
- The Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China
| | - Yi-Yi Liu
- The Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China
| | - Fu-Qi Zhu
- The Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China
| | - Mei-Juan Xiong
- The Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China
| | - Dong-Xia Hu
- Department of Rehabilitation Medicine, The Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China
| | - Wen-Jun Zhang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China
| |
Collapse
|
|
6
|
Khan T, Waseem R, Shahid M, Ansari J, Ahanger IA, Hassan I, Islam A. Recent advancement in therapeutic strategies for Alzheimer's disease: Insights from clinical trials. Ageing Res Rev 2023; 92:102113. [PMID: 37918760 DOI: 10.1016/j.arr.2023.102113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 10/16/2023] [Accepted: 10/27/2023] [Indexed: 11/04/2023]
Abstract
Alzheimer's disease (AD) is the most prevalent form of dementia, characterized by the presence of plaques of amyloid beta and Tau proteins. There is currently no permanent cure for AD; the only medications approved by the FDA for mild to moderate AD are cholinesterase inhibitors, NMDA receptor antagonists, and immunotherapies against core pathophysiology, that provide temporary relief only. Researchers worldwide have made significant attempts to find new targets and develop innovative therapeutic molecules to treat AD. The FDA-approved drugs are palliative and couldn't restore the damaged neuron cells of AD. Stem cells have self-differentiation properties, making them prospective therapeutics to treat AD. The promising results in pre-clinical studies of stem cell therapy for AD seek attention worldwide. Various stem cells, mainly mesenchymal stem cells, are currently in different phases of clinical trials and need more advancements to take this therapy to the translational level. Here, we review research from the past decade that has identified several hypotheses related to AD pathology. Moreover, this article also focuses on the recent advancement in therapeutic strategies for AD treatment including immunotherapy and stem cell therapy detailing the clinical trials that are currently undergoing development.
Collapse
Affiliation(s)
- Tanzeel Khan
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
| | - Rashid Waseem
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
| | - Mohammad Shahid
- Department of Basic Medical Sciences, College of Medicine, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Jaoud Ansari
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
| | - Ishfaq Ahmad Ahanger
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India; Department of Clinical Biochemistry, University of Kashmir,190006, India
| | - Imtaiyaz Hassan
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India
| | - Asimul Islam
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
| |
Collapse
|
|
7
|
Dave BP, Shah YB, Maheshwari KG, Mansuri KA, Prajapati BS, Postwala HI, Chorawala MR. Pathophysiological Aspects and Therapeutic Armamentarium of Alzheimer's Disease: Recent Trends and Future Development. Cell Mol Neurobiol 2023; 43:3847-3884. [PMID: 37725199 PMCID: PMC11407742 DOI: 10.1007/s10571-023-01408-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Accepted: 08/31/2023] [Indexed: 09/21/2023]
Abstract
Alzheimer's disease (AD) is the primary cause of dementia and is characterized by the death of brain cells due to the accumulation of insoluble amyloid plaques, hyperphosphorylation of tau protein, and the formation of neurofibrillary tangles within the cells. AD is also associated with other pathologies such as neuroinflammation, dysfunction of synaptic connections and circuits, disorders in mitochondrial function and energy production, epigenetic changes, and abnormalities in the vascular system. Despite extensive research conducted over the last hundred years, little is established about what causes AD or how to effectively treat it. Given the severity of the disease and the increasing number of affected individuals, there is a critical need to discover effective medications for AD. The US Food and Drug Administration (FDA) has approved several new drug molecules for AD management since 2003, but these drugs only provide temporary relief of symptoms and do not address the underlying causes of the disease. Currently, available medications focus on correcting the neurotransmitter disruption observed in AD, including cholinesterase inhibitors and an antagonist of the N-methyl-D-aspartate (NMDA) receptor, which temporarily alleviates the signs of dementia but does not prevent or reverse the course of AD. Research towards disease-modifying AD treatments is currently underway, including gene therapy, lipid nanoparticles, and dendrimer-based therapy. These innovative approaches aim to target the underlying pathological processes of AD rather than just managing the symptoms. This review discusses the novel aspects of pathogenesis involved in the causation of AD of AD and in recent developments in the therapeutic armamentarium for the treatment of AD such as gene therapy, lipid nanoparticles, and dendrimer-based therapy, and many more.
Collapse
Affiliation(s)
- Bhavarth P Dave
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Navrangpura, Ahmedabad, Gujarat, 380009, India
| | - Yesha B Shah
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Navrangpura, Ahmedabad, Gujarat, 380009, India
| | - Kunal G Maheshwari
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Navrangpura, Ahmedabad, Gujarat, 380009, India
| | - Kaif A Mansuri
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Navrangpura, Ahmedabad, Gujarat, 380009, India
| | - Bhadrawati S Prajapati
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Navrangpura, Ahmedabad, Gujarat, 380009, India
| | - Humzah I Postwala
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Navrangpura, Ahmedabad, Gujarat, 380009, India
| | - Mehul R Chorawala
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Navrangpura, Ahmedabad, Gujarat, 380009, India.
| |
Collapse
|
|
8
|
Bhatti JS, Khullar N, Mishra J, Kaur S, Sehrawat A, Sharma E, Bhatti GK, Selman A, Reddy PH. Stem cells in the treatment of Alzheimer's disease – Promises and pitfalls. Biochim Biophys Acta Mol Basis Dis 2023; 1869:166712. [DOI: https:/doi.org/10.1016/j.bbadis.2023.166712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/15/2025]
|
|
9
|
Bhatti JS, Khullar N, Mishra J, Kaur S, Sehrawat A, Sharma E, Bhatti GK, Selman A, Reddy PH. Stem cells in the treatment of Alzheimer's disease - Promises and pitfalls. Biochim Biophys Acta Mol Basis Dis 2023; 1869:166712. [PMID: 37030521 DOI: 10.1016/j.bbadis.2023.166712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Accepted: 03/31/2023] [Indexed: 04/10/2023]
Abstract
Alzheimer's disease (AD) is the most widespread form of neurodegenerative disorder that causes memory loss and multiple cognitive issues. The underlying mechanisms of AD include the build-up of amyloid-β and phosphorylated tau, synaptic damage, elevated levels of microglia and astrocytes, abnormal microRNAs, mitochondrial dysfunction, hormonal imbalance, and age-related neuronal loss. However, the etiology of AD is complex and involves a multitude of environmental and genetic factors. Currently, available AD medications only alleviate symptoms and do not provide a permanent cure. Therefore, there is a need for therapies that can prevent or reverse cognitive decline, brain tissue loss, and neural instability. Stem cell therapy is a promising treatment for AD because stem cells possess the unique ability to differentiate into any type of cell and maintain their self-renewal. This article provides an overview of the pathophysiology of AD and existing pharmacological treatments. This review article focuses on the role of various types of stem cells in neuroregeneration, the potential challenges, and the future of stem cell-based therapies for AD, including nano delivery and gaps in stem cell technology.
Collapse
Affiliation(s)
- Jasvinder Singh Bhatti
- Laboratory of Translational Medicine and Nanotherapeutics, Department of Human Genetics and Molecular Medicine, School of Health Sciences, Central University of Punjab, Bathinda, India.
| | - Naina Khullar
- Department of Zoology, Mata Gujri College, Fatehgarh Sahib, Punjab, India
| | - Jayapriya Mishra
- Laboratory of Translational Medicine and Nanotherapeutics, Department of Human Genetics and Molecular Medicine, School of Health Sciences, Central University of Punjab, Bathinda, India
| | - Satinder Kaur
- Laboratory of Translational Medicine and Nanotherapeutics, Department of Human Genetics and Molecular Medicine, School of Health Sciences, Central University of Punjab, Bathinda, India
| | - Abhishek Sehrawat
- Laboratory of Translational Medicine and Nanotherapeutics, Department of Human Genetics and Molecular Medicine, School of Health Sciences, Central University of Punjab, Bathinda, India
| | - Eva Sharma
- Laboratory of Translational Medicine and Nanotherapeutics, Department of Human Genetics and Molecular Medicine, School of Health Sciences, Central University of Punjab, Bathinda, India
| | - Gurjit Kaur Bhatti
- Department of Medical Lab Technology, University Institute of Applied Health Sciences, Chandigarh University, Mohali, India
| | - Ashley Selman
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
| | - P Hemachandra Reddy
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Department of Public Health, Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Department of Neurology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Department of Speech, Language, and Hearing Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Nutritional Sciences Department, College of Human Sciences, Texas Tech University, 1301 Akron Ave, Lubbock, TX 79409, USA.
| |
Collapse
|
|
10
|
Jeyaraman M, Rajendran RL, Muthu S, Jeyaraman N, Sharma S, Jha SK, Muthukanagaraj P, Hong CM, Furtado da Fonseca L, Santos Duarte Lana JF, Ahn BC, Gangadaran P. An update on stem cell and stem cell-derived extracellular vesicle-based therapy in the management of Alzheimer's disease. Heliyon 2023; 9:e17808. [PMID: 37449130 PMCID: PMC10336689 DOI: 10.1016/j.heliyon.2023.e17808] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 05/10/2023] [Accepted: 06/28/2023] [Indexed: 07/18/2023] Open
Abstract
Globally, neurological diseases pose a major burden to healthcare professionals in terms of the management and prevention of the disorder. Among neurological diseases, Alzheimer's disease (AD) accounts for 50%-70% of dementia and is the fifth leading cause of mortality worldwide. AD is a progressive, degenerative neurological disease, with the loss of neurons and synapses in the cerebral cortex and subcortical regions. The management of AD remains a debate among physicians as no standard and specific "disease-modifying" modality is available. The concept of 'Regenerative Medicine' is aimed at regenerating the degenerated neural tissues to reverse the pathology in AD. Genetically modified engineered stem cells modify the course of AD after transplantation into the brain. Extracellular vesicles (EVs) are an emerging new approach in cell communication that involves the transfer of cellular materials from parental cells to recipient cells, resulting in changes at the molecular and signaling levels in the recipient cells. EVs are a type of vesicle that can be transported between cells. Many have proposed that EVs produced from mesenchymal stem cells (MSCs) may have therapeutic promise in the treatment of AD. The biology of AD, as well as the potential applications of stem cells and their derived EVs-based therapy, were explored in this paper.
Collapse
Affiliation(s)
- Madhan Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai, Tamil Nadu, 600056, India
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, Uttar Pradesh, 201310, India
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow, Uttar Pradesh, 226010, India
| | - Ramya Lakshmi Rajendran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea
| | - Sathish Muthu
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, Uttar Pradesh, 201310, India
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow, Uttar Pradesh, 226010, India
- Department of Orthopedics, Government Dindigul Medical College and Hospital, Dindigul, Tamil Nadu, 624001, India
| | - Naveen Jeyaraman
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow, Uttar Pradesh, 226010, India
- Department of Orthopedics, Shri Sathya Sai Medical College and Research Institute, Sri Balaji Vidyapeeth, Chengalpet, Tamil Nadu, 603108, India
| | - Shilpa Sharma
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow, Uttar Pradesh, 226010, India
- Department of Paediatric Surgery, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Saurabh Kumar Jha
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, Uttar Pradesh, 201310, India
| | - Purushothaman Muthukanagaraj
- Department of Internal Medicine & Psychiatry, SUNY-Upstate Binghamton Clinical Campus, Binghamton, NY, 13904, USA
| | - Chae Moon Hong
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea
| | - Lucas Furtado da Fonseca
- Department of Orthopedics, The Federal University of São Paulo, São Paulo, 04023-062, SP, Brazil
| | | | - Byeong-Cheol Ahn
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea
| | - Prakash Gangadaran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea
| |
Collapse
|
|
11
|
Li J, Zhang F, Zhao L, Dong C. Microbiota-gut-brain axis and related therapeutics in Alzheimer's disease: prospects for multitherapy and inflammation control. Rev Neurosci 2023:revneuro-2023-0006. [PMID: 37076953 DOI: 10.1515/revneuro-2023-0006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 03/26/2023] [Indexed: 04/21/2023]
Abstract
Alzheimer's disease (AD) is the most common type of dementia in the elderly and causes neurodegeneration, leading to memory loss, behavioral disorder, and psychiatric impairment. One potential mechanism contributing to the pathogenesis of AD may be the imbalance in gut microbiota, local and systemic inflammation, and dysregulation of the microbiota-gut-brain axis (MGBA). Most of the AD drugs approved for clinical use today are symptomatic treatments that do not improve AD pathologic changes. As a result, researchers are exploring novel therapeutic modalities. Treatments involving the MGBA include antibiotics, probiotics, transplantation of fecal microbiota, botanical products, and others. However, single-treatment modalities are not as effective as expected, and a combination therapy is gaining momentum. The purpose of this review is to summarize recent advances in MGBA-related pathological mechanisms and treatment modalities in AD and to propose a new concept of combination therapy. "MGBA-based multitherapy" is an emerging view of treatment in which classic symptomatic treatments and MGBA-based therapeutic modalities are used in combination. Donepezil and memantine are two commonly used drugs in AD treatment. On the basis of the single/combined use of these two drugs, two/more additional drugs and treatment modalities that target the MGBA are chosen based on the characteristics of the patient's condition as an adjuvant treatment, as well as the maintenance of good lifestyle habits. "MGBA-based multitherapy" offers new insights for the treatment of cognitive impairment in AD patients and is expected to show good therapeutic results.
Collapse
Affiliation(s)
- Jiahao Li
- Department of Neurology, The First Affiliated Hospital, Dalian Medical University, No. 222 Zhongshan Road, Dalian 116011, China
| | - Feng Zhang
- Department of Neurology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China
| | - Li Zhao
- Department of Neurology, The First Affiliated Hospital, Dalian Medical University, No. 222 Zhongshan Road, Dalian 116011, China
| | - Chunbo Dong
- Department of Neurology, The First Affiliated Hospital, Dalian Medical University, No. 222 Zhongshan Road, Dalian 116011, China
| |
Collapse
|
|
12
|
Bai Y, Wang Z, Yu L, Dong K, Cheng L, Zhu R. The enhanced generation of motor neurons from mESCs by MgAl layered double hydroxide nanoparticles. Biomed Mater 2023; 18. [PMID: 36898160 DOI: 10.1088/1748-605x/acc375] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Accepted: 03/10/2023] [Indexed: 03/12/2023]
Abstract
The committed differentiation of stem cells into neurons is a promising therapeutic strategy for neurological diseases. Predifferentiation of transplanted stem cells into neural precursors could enhance their utilization and control the direction of differentiation. Embryonic stem cells with totipotency can differentiate into specific nerve cells under appropriate external induction conditions. Layered double hydroxide (LDH) nanoparticles have been proven to regulate the pluripotency of mouse ESCs (mESCs), and LDH could be used as carrier in neural stem cells for nerve regeneration. Hence, we sought to study the effects of LDH without loaded factors on mESCs neurogenesis in this work. A series of characteristics analyses indicated the successful construction of LDH nanoparticles. LDH nanoparticles that may adhere to the cell membranes had insignificant effect on cell proliferation and apoptosis. The enhanced differentiation of mESCs into motor neurons by LDH was systematically validated by immunofluorescent staining, quantitative real-time PCR analysis and western blot analysis. In addition, transcriptome sequencing analysis and mechanism verification elucidated the significant regulatory roles of focal adhesion signaling pathway in the enhanced mESCs neurogenesis by LDH. Taken together, the functional validation of inorganic LDH nanoparticles promoting motor neurons differentiation provide a novel strategy and therapeutic prospect for the clinical transition of neural regeneration.
Collapse
Affiliation(s)
- Yuxin Bai
- Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital affiliated to Tongji University, School of Life Science and Technology, Tongji University, Shanghai 200065, People's Republic of China
- Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200065, People's Republic of China
| | - Zhaojie Wang
- Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital affiliated to Tongji University, School of Life Science and Technology, Tongji University, Shanghai 200065, People's Republic of China
- Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200065, People's Republic of China
| | - Liqun Yu
- Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital affiliated to Tongji University, School of Life Science and Technology, Tongji University, Shanghai 200065, People's Republic of China
- Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200065, People's Republic of China
| | - Kun Dong
- Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital affiliated to Tongji University, School of Life Science and Technology, Tongji University, Shanghai 200065, People's Republic of China
- Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200065, People's Republic of China
| | - Liming Cheng
- Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital affiliated to Tongji University, School of Life Science and Technology, Tongji University, Shanghai 200065, People's Republic of China
- Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200065, People's Republic of China
| | - Rongrong Zhu
- Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital affiliated to Tongji University, School of Life Science and Technology, Tongji University, Shanghai 200065, People's Republic of China
- Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200065, People's Republic of China
| |
Collapse
|
|
13
|
Zhou Z, Shi B, Xu Y, Zhang J, liu X, Zhou X, Feng B, Ma J, Cui H. Neural stem/progenitor cell therapy for Alzheimer disease in preclinical rodent models: a systematic review and meta-analysis. Stem Cell Res Ther 2023; 14:3. [PMID: 36600321 PMCID: PMC9814315 DOI: 10.1186/s13287-022-03231-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 12/25/2022] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Alzheimer's disease (AD) is a common progressive neurodegenerative disease characterized by memory impairments, and there is no effective therapy. Neural stem/progenitor cell (NSPC) has emerged as potential novel therapy for AD, and we aim to explore whether neural stem/progenitor cell therapy was effective for rodent models of AD. METHODS We searched PubMed, Embase, Cochrane Library and Web of Science up to December 6, 2022. The outcomes included cognitive function, pathological features and BDNF. The GetData Graph Digitizer software (version 2.26) was applied to extract numerical values, and RevMan 5.3 and Stata 16 were used to analyze data. The SYRCLE risk of bias tool was used to assess study quality. RESULTS We evaluated 22 mice studies and 8 rat studies. Compared to control groups, cognitive function of NSPC groups of both mice studies (SMD = - 1.96, 95% CI - 2.47 to - 1.45, I2 = 75%, P < 0.00001) and rat studies (SMD = - 1.35, 95% CI - 2.11 to - 0.59, I2 = 77%, P = 0.0005) was apparently improved. In mice studies, NSPC group has lower Aβ deposition (SMD = - 0.96, 95% CI - 1.40 to - 0.52, P < 0.0001) and p-tau level (SMD = - 4.94, 95% CI - 7.29 to - 2.95, P < 0.0001), higher synaptic density (SMD = 2.02, 95% CI 0.50-3.55, P = 0.009) and BDNF (SMD = 1.69, 95% CI 0.61-2.77, P = 0.002). Combined with nanoformulation (SMD = - 1.29, 95% CI - 2.26 to - 0.32, I2 = 65%, P = 0.009) and genetically modified (SMD = - 1.29, 95% CI - 1.92 to - 0.66, I2 = 60%, P < 0.0001) could improve the effect of NSPC. In addition, both xenogeneic and allogeneic transplant of NSPC could reverse the cognitive impairment of AD animal models. CONCLUSIONS Our results suggested that NSPC therapy could improve the cognitive function and slow down the progression of AD. Due to the limitations of models, more animal trials and clinical trials are needed.
Collapse
Affiliation(s)
- Zijing Zhou
- grid.256883.20000 0004 1760 8442Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017 Hebei Province China ,grid.256883.20000 0004 1760 8442Hebei Research Center for Stem Cell Medical Translational Engineering, Hebei Medical University, Shijiazhuang, 050017 Hebei Province China
| | - Ben Shi
- grid.256883.20000 0004 1760 8442Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017 Hebei Province China ,grid.256883.20000 0004 1760 8442Hebei Research Center for Stem Cell Medical Translational Engineering, Hebei Medical University, Shijiazhuang, 050017 Hebei Province China
| | - Yaxing Xu
- grid.256883.20000 0004 1760 8442Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017 Hebei Province China ,grid.256883.20000 0004 1760 8442Hebei Research Center for Stem Cell Medical Translational Engineering, Hebei Medical University, Shijiazhuang, 050017 Hebei Province China
| | - Jinyu Zhang
- grid.256883.20000 0004 1760 8442Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017 Hebei Province China ,grid.256883.20000 0004 1760 8442Hebei Research Center for Stem Cell Medical Translational Engineering, Hebei Medical University, Shijiazhuang, 050017 Hebei Province China
| | - Xin liu
- grid.256883.20000 0004 1760 8442Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017 Hebei Province China ,grid.256883.20000 0004 1760 8442Hebei Research Center for Stem Cell Medical Translational Engineering, Hebei Medical University, Shijiazhuang, 050017 Hebei Province China
| | - Xinghong Zhou
- grid.256883.20000 0004 1760 8442Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017 Hebei Province China ,grid.256883.20000 0004 1760 8442Hebei Research Center for Stem Cell Medical Translational Engineering, Hebei Medical University, Shijiazhuang, 050017 Hebei Province China
| | - Baofeng Feng
- grid.256883.20000 0004 1760 8442Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017 Hebei Province China ,grid.256883.20000 0004 1760 8442Hebei Research Center for Stem Cell Medical Translational Engineering, Hebei Medical University, Shijiazhuang, 050017 Hebei Province China ,grid.256883.20000 0004 1760 8442Human Anatomy Department, Hebei Medical University, Shijiazhuang, 050017 Hebei Province China
| | - Jun Ma
- Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China. .,Hebei Research Center for Stem Cell Medical Translational Engineering, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China. .,Human Anatomy Department, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China.
| | - Huixian Cui
- grid.256883.20000 0004 1760 8442Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017 Hebei Province China ,grid.256883.20000 0004 1760 8442Hebei Research Center for Stem Cell Medical Translational Engineering, Hebei Medical University, Shijiazhuang, 050017 Hebei Province China ,grid.256883.20000 0004 1760 8442Human Anatomy Department, Hebei Medical University, Shijiazhuang, 050017 Hebei Province China
| |
Collapse
|
|
14
|
Elzayat EM, Shahien SA, El-Sherif AA, Hosney M. miRNAs and Stem Cells as Promising Diagnostic and Therapeutic Targets for Alzheimer's Disease. J Alzheimers Dis 2023; 94:S203-S225. [PMID: 37212107 PMCID: PMC10473110 DOI: 10.3233/jad-221298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/30/2023] [Indexed: 05/23/2023]
Abstract
Alzheimer's disease (AD) is a cumulative progressive neurodegenerative disease characterized mainly by impairment in cognitive functions accompanied by memory loss, disturbance in behavior and personality, and difficulties in learning. Although the main causes of AD pathogenesis are not fully understood yet, amyloid-β peptides and tau proteins are supposed to be responsible for AD onset and pathogenesis. Various demographic, genetic, and environmental risk factors are involved in AD onset and pathogenesis such as age, gender, several genes, lipids, malnutrition, and poor diet. Significant changes were observed in microRNA (miRNA) levels between normal and AD cases giving hope for a diagnostic procedure for AD through a simple blood test. As yet, only two classes of AD therapeutic drugs are approved by FDA. They are classified as acetylcholinesterase inhibitors and N-methyl-D-aspartate antagonists (NMDA). Unfortunately, they can only treat the symptoms but cannot cure AD or stop its progression. New therapeutic approaches were developed for AD treatment including acitretin due to its ability to cross blood-brain barrier in the brain of rats and mice and induce the expression of ADAM 10 gene, the α-secretase of human amyloid-β protein precursor, stimulating the non-amyloidogenic pathway for amyloid-β protein precursor processing resulting in amyloid-β reduction. Also stem cells may have a crucial role in AD treatment as they can improve cognitive functions and memory in AD rats through regeneration of damaged neurons. This review spotlights on promising diagnostic techniques such as miRNAs and therapeutic approaches such as acitretin and/or stem cells keeping in consideration AD pathogenesis, stages, symptoms, and risk factors.
Collapse
Affiliation(s)
- Emad M. Elzayat
- Zoology Department, Faculty of Science, Cairo University, Giza, Egypt
| | - Sherif A. Shahien
- Biotechnology/Bimolecular Chemistry Program, Faculty of Science, Helwan University, Cairo, Egypt
| | - Ahmed A. El-Sherif
- Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt
| | - Mohamed Hosney
- Zoology Department, Faculty of Science, Cairo University, Giza, Egypt
| |
Collapse
|
|
15
|
Abu-El-Rub E, Khasawneh RR, Almahasneh FA, Aloud BM, Zegallai HM. The Molecular and Functional Changes of Neural Stem Cells in Alzheimer's Disease: Can They be Reinvigorated to Conduct Neurogenesis. Curr Stem Cell Res Ther 2023; 18:580-594. [PMID: 36045542 DOI: 10.2174/1574888x17666220831105257] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 07/04/2022] [Accepted: 07/19/2022] [Indexed: 11/22/2022]
Abstract
Alzheimer's disease (AD) is considered one of the most complicated neurodegenerative disorders, and it is associated with progressive memory loss and remarkable neurocognitive dysfunction that negatively impacts the ability to perform daily living activities. AD accounts for an estimated 60-80% of dementia cases. AD's previously known pathological basis is the deposition of amyloid β (Aβ) aggregates and the formation of neurofibrillary tangles by tau hyperphosphorylation in the cell bodies of neurons that are located in the hippocampus, neocortex, and certain other regions of the cerebral hemispheres and limbic system. The lack of neurotransmitter acetylcholine and the activation of oxidative stress cascade may also contribute to the pathogenesis of AD. These pathological events can lead to irreversible loss of neuronal networks and the emergence of memory impairment and cognitive dysfunction that can engender an abnormal change in the personality. AD cannot be cured, and to some extent, the prescribed medications can only manage the symptoms associated with this disease. Several studies have reported that the regenerative abilities of neural stem/progenitor cells (NSCs) remarkably decline in AD, which disturbs the balancing power to control its progression. Exogenous infusion or endogenous activation of NSCs may be the ultimate solution to restore the neuronal networks in the brain of AD patients and regenerate the damaged areas responsible for memory and cognition. In this mini-review, we will touch upon the fate of NSCs in AD and the utilization of neurogenesis using modified NSCs to restore cognitive functions in AD.
Collapse
Affiliation(s)
- Ejlal Abu-El-Rub
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan
| | - Ramada R Khasawneh
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan
| | - Fatimah A Almahasneh
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan
| | - Basma Milad Aloud
- Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Canada
| | - Hana M Zegallai
- Department of Pharmacology & Therapeutics, University of Manitoba, Winnipeg, Canada
- DREAM, Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada
| |
Collapse
|
|
16
|
Srivastava R, Li A, Datta T, Jha NK, Talukder S, Jha SK, Chen ZS. Advances in stromal cell therapy for management of Alzheimer’s disease. Front Pharmacol 2022; 13:955401. [PMID: 36267273 PMCID: PMC9576849 DOI: 10.3389/fphar.2022.955401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Accepted: 09/08/2022] [Indexed: 11/13/2022] Open
Abstract
Deposition of misfolded proteins and synaptic failure affects the brain in Alzheimer’s disease (AD). Its progression results in amnesia and cognitive impairment. Absence of treatment is due to excessive loss of neurons in the patients and the delayed effects of drugs. The enhanced pluripotency, proliferation, differentiation, and recombination characteristics of stromal cells into nerve cells and glial cells present them as a potential treatment for AD. Successful evidence of action in animal models along with positive results in preclinical studies further encourage its utilization for AD treatment. With regard to humans, cell replacement therapy involving mesenchymal stromal cells, induced-pluripotent stromal cells, human embryonic stromal cells, and neural stems show promising results in clinical trials. However, further research is required prior to its use as stromal cell therapy in AD related disorders. The current review deals with the mechanism of development of anomalies such as Alzheimer’s and the prospective applications of stromal cells for treatment.
Collapse
Affiliation(s)
- Rashi Srivastava
- Chemical and Biochemical Engineering, Indian Institute of Technology, Patna, India
| | - Aidong Li
- Department of Rehabilitation, The Second People’s Hospital of Shenzhen, Shenzhen, China
| | - Tirtharaj Datta
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, India
| | - Niraj Kumar Jha
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, India
| | - Salehikram Talukder
- Institute for Biotechnology, St. John’s University, New York City, NY, United States
| | - Saurabh Kumar Jha
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, India
- Department of Biotechnology, School of Applied and Life Sciences, Uttaranchal University, Dehradun, India
- Department of Biotechnology Engineering and Food Technology, Chandigarh University, Mohali, India
- *Correspondence: Saurabh Kumar Jha, ; Zhe-Sheng Chen,
| | - Zhe-Sheng Chen
- Institute for Biotechnology, St. John’s University, New York City, NY, United States
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, New York City, NY, United States
- *Correspondence: Saurabh Kumar Jha, ; Zhe-Sheng Chen,
| |
Collapse
|
|
17
|
Yue C, Feng S, Chen Y, Jing N. The therapeutic prospects and challenges of human neural stem cells for the treatment of Alzheimer's Disease. CELL REGENERATION (LONDON, ENGLAND) 2022; 11:28. [PMID: 36050613 PMCID: PMC9437172 DOI: 10.1186/s13619-022-00128-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 07/15/2022] [Indexed: 06/15/2023]
Abstract
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder associated with aging. Due to its insidious onset, protracted progression, and unclear pathogenesis, it is considered one of the most obscure and intractable brain disorders, and currently, there are no effective therapies for it. Convincing evidence indicates that the irreversible decline of cognitive abilities in patients coincides with the deterioration and degeneration of neurons and synapses in the AD brain. Human neural stem cells (NSCs) hold the potential to functionally replace lost neurons, reinforce impaired synaptic networks, and repair the damaged AD brain. They have therefore received extensive attention as a possible source of donor cells for cellular replacement therapies for AD. Here, we review the progress in NSC-based transplantation studies in animal models of AD and assess the therapeutic advantages and challenges of human NSCs as donor cells. We then formulate a promising transplantation approach for the treatment of human AD, which would help to explore the disease-modifying cellular therapeutic strategy for the treatment of human AD.
Collapse
Affiliation(s)
- Chunmei Yue
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.
- Department of Biological Sciences, School of Science, Xi'an Jiaotong-Liverpool University, Suzhou, 215000, China.
| | - Su Feng
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China
- Bioland Laboratory/Guangzhou Laboratory, Guangzhou, 510005, China
| | - Yingying Chen
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China
| | - Naihe Jing
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.
- Bioland Laboratory/Guangzhou Laboratory, Guangzhou, 510005, China.
- CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
- School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
| |
Collapse
|
|
18
|
Role and Function of Mesenchymal Stem Cells on Fibroblast in Cutaneous Wound Healing. Biomedicines 2022; 10:biomedicines10061391. [PMID: 35740413 PMCID: PMC9219688 DOI: 10.3390/biomedicines10061391] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Revised: 06/06/2022] [Accepted: 06/10/2022] [Indexed: 11/24/2022] Open
Abstract
Skin wounds often repair themselves completely over time; however, this is true only for healthy individuals. Although various studies are being conducted to improve wound-healing therapy outcomes, the mechanisms of wound healing and regeneration are not completely understood yet. In recent years, mesenchymal stem cells (MSCs) have been reported to contribute significantly to wound healing and regeneration. Understanding the function of MSCs will help to elucidate the fundamentals of wound healing. MSCs are multipotent stem cells that are used in regenerative medicine for their ability to self-renew and differentiate into bone, fat, and cartilage, with few ethical problems associated with cell harvesting. Additionally, they have anti-inflammatory and immunomodulatory properties and antifibrotic effects via paracrine signaling, and many studies have been conducted to use them to treat graft-versus-host disease, inflammatory bowel disease, and intractable cutaneous wounds. Many substances derived from MSCs are involved in the wound-healing process, and specific cascades and pathways have been elucidated. This review aims to explain the fundamental role of MSCs in wound healing and the effects of MSCs on fibroblasts.
Collapse
|
|
19
|
Zhao H, Wei J, Du Y, Chen P, Liu X, Liu H. Improved cognitive impairments by silencing DMP1 via enhancing the proliferation of neural progenitor cell in Alzheimer-like mice. Aging Cell 2022; 21:e13601. [PMID: 35366382 PMCID: PMC9124312 DOI: 10.1111/acel.13601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 03/08/2022] [Accepted: 03/17/2022] [Indexed: 11/28/2022] Open
Abstract
Alzheimer's disease (AD) is age-related progressive neurological dysfunction. Limited clinical benefits for current treatments indicate an urgent need for novel therapeutic strategies. Previous transcriptomic analysis showed that DMP1 expression level was increased in AD model animals whereas it can induce cell-cycle arrest in several cell lines. However, whether the cell-cycle arrest of neural progenitor cell induced by DMP1 affects cognitive function in Alzheimer-like mice still remains unknown. The objective of our study is to explore the issue. We found that DMP1 is correlated with cognitive function based on the clinical genomic analysis of ADNI database. The negative role of DMP1 on neural progenitor cell (NPC) proliferation was revealed by silencing and overexpressing DMP1 in vitro. Furthermore, silencing DMP1 could increase the number of NPCs and improve cognitive function in Alzheimer-like mice, through decreasing P53 and P21 levels, which suggested that DMP1-induced cell-cycle arrest could influence cognitive function.
Collapse
Affiliation(s)
- Huimin Zhao
- Center of Drug Metabolism and PharmacokineticsChina Pharmaceutical UniversityNanjingChina
| | - Jie Wei
- Center of Drug Metabolism and PharmacokineticsChina Pharmaceutical UniversityNanjingChina
| | - Yanan Du
- Center of Drug Metabolism and PharmacokineticsChina Pharmaceutical UniversityNanjingChina
| | - Peipei Chen
- Center of Drug Metabolism and PharmacokineticsChina Pharmaceutical UniversityNanjingChina
| | - Xiaoquan Liu
- Center of Drug Metabolism and PharmacokineticsChina Pharmaceutical UniversityNanjingChina
| | - Haochen Liu
- Center of Drug Metabolism and PharmacokineticsChina Pharmaceutical UniversityNanjingChina
| | | |
Collapse
|
|
20
|
Karvelas N, Bennett S, Politis G, Kouris NI, Kole C. Advances in stem cell therapy in Alzheimer's disease: a comprehensive clinical trial review. Stem Cell Investig 2022; 9:2. [PMID: 35280344 PMCID: PMC8898169 DOI: 10.21037/sci-2021-063] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 01/27/2022] [Indexed: 07/30/2023]
Abstract
Alzheimer's disease (AD) is the most common type of dementia responsible for more than 121,499 deaths from AD in 2019 making AD the sixth-leading cause in the United States. AD is a progressive neurodegenerative disorder characterized by decline of memory, behavioral impairments that affects a person's ability to function independently ultimately leading to death. The current pressing need for a treatment for (AD) and advances in the field of cell therapy, has rendered stem cell therapeutics a promising field of research. Despite advancements in stem cell technology, confirmed by encouraging pre-clinical utilization of stem cells in AD animal models, the number of clinical trials evaluating the efficacy of stem cell therapy is limited, with the results of many ongoing clinical trials on cell therapy for AD still pending. Mesenchymal stem cells (MSCs) have been the main focus in these studies, reporting encouraging results concerning safety profile, however their efficacy remains unproven. In the current article we review the latest advances regarding different sources of stem cell therapy and present a comprehensive list of every available clinical trial in national and international registries. Finally, we discuss drawbacks arising from AD pathology and technical limitations that hinder the transition of stem cell technology from bench to bedside. Our findings emphasize the need to increase clinical trials towards uncovering the mode of action and the underlying therapeutic mechanisms of transplanted cells as well as the molecular mechanisms controlling regeneration and neuronal microenvironment.
Collapse
Affiliation(s)
- Nikolaos Karvelas
- Faculty of Medicine, National and Kapodistrian University of Athens, Athina, Greece
| | | | - Georgios Politis
- Faculty of Medicine, National and Kapodistrian University of Athens, Athina, Greece
| | | | - Christo Kole
- Faculty of Medicine, National and Kapodistrian University of Athens, Athina, Greece
| |
Collapse
|
|
21
|
Qin C, Wang K, Zhang L, Bai L. Stem cell therapy for Alzheimer's disease: An overview of experimental models and reality. Animal Model Exp Med 2022; 5:15-26. [PMID: 35229995 PMCID: PMC8879630 DOI: 10.1002/ame2.12207] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 01/04/2022] [Accepted: 01/12/2022] [Indexed: 11/06/2022] Open
Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder. The pathology of AD is characterized by extracellular amyloid beta (Aβ) plaques, neurofibrillary tangles composed 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 weaknesses 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 challenges for its clinical application in the future.
Collapse
Affiliation(s)
- Chuan Qin
- Institute of Laboratory Animal SciencesChinese 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
| | - Kewei Wang
- Institute of Laboratory Animal SciencesChinese 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
| | - Ling Zhang
- Institute of Laboratory Animal SciencesChinese 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
| | - Lin Bai
- Institute of Laboratory Animal SciencesChinese 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
| |
Collapse
|
|
22
|
Chiavellini P, Canatelli-Mallat M, Lehmann M, Goya RG, Morel GR. Therapeutic potential of glial cell line-derived neurotrophic factor and cell reprogramming for hippocampal-related neurological disorders. Neural Regen Res 2022; 17:469-476. [PMID: 34380873 PMCID: PMC8504380 DOI: 10.4103/1673-5374.320966] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Hippocampus serves as a pivotal role in cognitive and emotional processes, as well as in the regulation of the hypothalamus-pituitary axis. It is known to undergo mild neurodegenerative changes during normal aging and severe atrophy in Alzheimer’s disease. Furthermore, dysregulation in the hippocampal function leads to epilepsy and mood disorders. In the first section, we summarized the most salient knowledge on the role of glial cell-line-derived neurotrophic factor and its receptors focused on aging, cognition and neurodegenerative and hippocampal-related neurological diseases mentioned above. In the second section, we reviewed the therapeutic approaches, particularly gene therapy, using glial cell-line-derived neurotrophic factor or its gene, as a key molecule in the development of neurological disorders. In the third section, we pointed at the potential of regenerative medicine, as an emerging and less explored strategy for the treatment of hippocampal disorders. We briefly reviewed the use of partial reprogramming to restore brain functions, non-neuronal cell reprogramming to generate neural stem cells, and neural progenitor cells as source-specific neuronal types to be implanted in animal models of specific neurodegenerative disorders.
Collapse
Affiliation(s)
- Priscila Chiavellini
- Biochemistry Research Institute of La Plata (INIBIOLP)-Histology and Embryology B, School of Medical Sciences, National University of La Plata (UNLP), La Plata, Buenos Aires, Argentina
| | - Martina Canatelli-Mallat
- Biochemistry Research Institute of La Plata (INIBIOLP)-Histology and Embryology B, School of Medical Sciences, National University of La Plata (UNLP), La Plata, Buenos Aires, Argentina
| | - Marianne Lehmann
- Biochemistry Research Institute of La Plata (INIBIOLP)-Histology and Embryology B, School of Medical Sciences, National University of La Plata (UNLP), La Plata, Buenos Aires, Argentina
| | - Rodolfo G Goya
- Biochemistry Research Institute of La Plata (INIBIOLP)-Histology and Embryology B, School of Medical Sciences, National University of La Plata (UNLP), La Plata, Buenos Aires, Argentina
| | - Gustavo R Morel
- Biochemistry Research Institute of La Plata (INIBIOLP)-Histology and Embryology B, School of Medical Sciences, National University of La Plata (UNLP), La Plata, Buenos Aires, Argentina
| |
Collapse
|
|
23
|
Zhang HA, Yuan CX, Liu KF, Yang QF, Zhao J, Li H, Yang QH, Song D, Quan ZZ, Qing H. Neural stem cell transplantation alleviates functional cognitive deficits in a mouse model of tauopathy. Neural Regen Res 2022; 17:152-162. [PMID: 34100451 PMCID: PMC8451553 DOI: 10.4103/1673-5374.314324] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
The mechanisms of the transplantation of neural stem cells (NSCs) in the treatment of Alzheimer’s disease remain poorly understood. In this study, NSCs were transplanted into the hippocampal CA1 region of the rTg (tau P301L) 4510 mouse model, a tauopathy model that is thought to reflect the tau pathology associated with Alzheimer’s disease. The results revealed that NSC transplantation reduced the abnormal aggregation of tau, resulting in significant improvements in the short-term memory of the tauopathy model mice. Compared with wild-type and phosphate-buffered saline (PBS)-treated mice, mice that received NSC transplantations were characterized by changes in the expression of multiple proteins in brain tissue, particularly those related to the regulation of tau aggregation or misfolding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) function analysis revealed that these proteins were primarily enriched in pathways associated with long-term potentiation, neurogenesis, and other neurobiological processes. Changes in the expression levels of key proteins were verified by western blot assays. These data provided clues to improve the understanding of the functional capacity associated with NSC transplantation in Alzheimer’s disease treatment. This study was approved by the Beijing Animal Ethics Association and Ethics Committee of Beijing Institute of Technology (approval No. SYXK-BIT-school of life science-2017-M03) in 2017.
Collapse
Affiliation(s)
- He-Ao Zhang
- Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing, China
| | - Chun-Xu Yuan
- Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing, China
| | - Ke-Fu Liu
- Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing, China
| | - Qi-Fan Yang
- Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing, China
| | - Juan Zhao
- Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing, China
| | - Hui Li
- Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing, China
| | - Qing-Hu Yang
- Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing, China
| | - Da Song
- Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing, China
| | - Zhen-Zhen Quan
- Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing, China
| | - Hong Qing
- Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing, China
| |
Collapse
|
|
24
|
Sharma NS, Karan A, Lee D, Yan Z, Xie J. Advances in Modeling Alzheimer's Disease In Vitro. ADVANCED NANOBIOMED RESEARCH 2021. [DOI: 10.1002/anbr.202100097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Affiliation(s)
- Navatha Shree Sharma
- Department of Surgery-Transplant and Mary & Dick Holland Regenerative Medicine Program University of Nebraska Medical Center Omaha NE 68198 USA
| | - Anik Karan
- Department of Surgery-Transplant and Mary & Dick Holland Regenerative Medicine Program University of Nebraska Medical Center Omaha NE 68198 USA
| | - Donghee Lee
- Department of Surgery-Transplant and Mary & Dick Holland Regenerative Medicine Program University of Nebraska Medical Center Omaha NE 68198 USA
| | - Zheng Yan
- Department of Mechanical & Aerospace Engineering and Department of Biomedical Biological and Chemical Engineering University of Missouri Columbia MO 65211 USA
| | - Jingwei Xie
- Department of Surgery-Transplant and Mary & Dick Holland Regenerative Medicine Program University of Nebraska Medical Center Omaha NE 68198 USA
- Department of Mechanical and Materials Engineering College of Engineering University of Nebraska Lincoln Lincoln NE 68588 USA
| |
Collapse
|
|
25
|
Engrafted stem cell therapy for Alzheimer's disease: A promising treatment strategy with clinical outcome. J Control Release 2021; 338:837-857. [PMID: 34509587 DOI: 10.1016/j.jconrel.2021.09.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 09/06/2021] [Accepted: 09/07/2021] [Indexed: 12/27/2022]
Abstract
To date, although the microscopic alterations present in Alzheimer's disease (AD) have been well known for over a century only a handful of symptomatic treatments have been developed which are a far cry from a full cure providing volatile benefits. In this context, the intervention of stem cell therapy (SCT) has been proposed as an auxiliary treatment for AD as suggested by the rising number of pre-clinical studies that stem cell engraftment could provide an exciting future treatment regimen against neurodegeneration. Although, most of the primary enthusiasm about this approach was based on replacing deteriorating neurons, the latest studies have implied that the positive modulations fostered by stem cells are fuelled by bystander effects. Present review provides a detailed update on stem cell therapy for AD along with meticulous discussion regarding challenges in developing different stem cells from an aspect of experiment to clinical research and their potential in the milieu of AD hallmarks. Specifically, we focus and provide in depth view on recent advancements in the discipline of SCT aiming to repopulate or regenerate the degenerating neuronal circuitry in AD using stem-cell-on-a-chip and 3D bioprinting techniques. The focus is specifically on the successful restoration of cognitive functions upon engraftment of stem cells on in vivo models for the benefit of the current researchers and their understanding about the status of SCT in AD and finally summarizing on what future holds for SCT in the treatment of AD.
Collapse
|
|
26
|
Zhao L, Liu JW, Shi HY, Ma YM. Neural stem cell therapy for brain disease. World J Stem Cells 2021; 13:1278-1292. [PMID: 34630862 PMCID: PMC8474718 DOI: 10.4252/wjsc.v13.i9.1278] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 05/28/2021] [Accepted: 08/27/2021] [Indexed: 02/06/2023] Open
Abstract
Brain diseases, including brain tumors, neurodegenerative disorders, cerebrovascular diseases, and traumatic brain injuries, are among the major disorders influencing human health, currently with no effective therapy. Due to the low regeneration capacity of neurons, insufficient secretion of neurotrophic factors, and the aggravation of ischemia and hypoxia after nerve injury, irreversible loss of functional neurons and nerve tissue damage occurs. This damage is difficult to repair and regenerate the central nervous system after injury. Neural stem cells (NSCs) are pluripotent stem cells that only exist in the central nervous system. They have good self-renewal potential and ability to differentiate into neurons, astrocytes, and oligodendrocytes and improve the cellular microenvironment. NSC transplantation approaches have been made for various neurodegenerative disorders based on their regenerative potential. This review summarizes and discusses the characteristics of NSCs, and the advantages and effects of NSCs in the treatment of brain diseases and limitations of NSC transplantation that need to be addressed for the treatment of brain diseases in the future.
Collapse
Affiliation(s)
- Lan Zhao
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300381, China.
| | - Jian-Wei Liu
- Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Hui-Yan Shi
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300381, China
| | - Ya-Min Ma
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300381, China
| |
Collapse
|
|
27
|
Chan HJ, Yanshree, Roy J, Tipoe GL, Fung ML, Lim LW. Therapeutic Potential of Human Stem Cell Implantation in Alzheimer's Disease. Int J Mol Sci 2021; 22:10151. [PMID: 34576314 PMCID: PMC8471075 DOI: 10.3390/ijms221810151] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 09/14/2021] [Accepted: 09/15/2021] [Indexed: 12/27/2022] Open
Abstract
Alzheimer's disease (AD) is a progressive debilitating neurodegenerative disease and the most common form of dementia in the older population. At present, there is no definitive effective treatment for AD. Therefore, researchers are now looking at stem cell therapy as a possible treatment for AD, but whether stem cells are safe and effective in humans is still not clear. In this narrative review, we discuss both preclinical studies and clinical trials on the therapeutic potential of human stem cells in AD. Preclinical studies have successfully differentiated stem cells into neurons in vitro, indicating the potential viability of stem cell therapy in neurodegenerative diseases. Preclinical studies have also shown that stem cell therapy is safe and effective in improving cognitive performance in animal models, as demonstrated in the Morris water maze test and novel object recognition test. Although few clinical trials have been completed and many trials are still in phase I and II, the initial results confirm the outcomes of the preclinical studies. However, limitations like rejection, tumorigenicity, and ethical issues are still barriers to the advancement of stem cell therapy. In conclusion, the use of stem cells in the treatment of AD shows promise in terms of effectiveness and safety.
Collapse
Affiliation(s)
| | | | | | | | | | - Lee Wei Lim
- School of Biomedical, Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; (H.J.C.); (Y.); (J.R.); (G.L.T.); (M.-L.F.)
| |
Collapse
|
|
28
|
Aishwarya L, Arun D, Kannan S. Stem cells as a potential therapeutic option for treating neurodegenerative diseases. Curr Stem Cell Res Ther 2021; 17:590-605. [PMID: 35135464 DOI: 10.2174/1574888x16666210810105136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/27/2021] [Accepted: 06/01/2021] [Indexed: 11/22/2022]
Abstract
In future, neurodegenerative diseases will take over cancer's place and become the major cause of death in the world, especially in developed countries. Advancements in the medical field and its facilities have led to an increase in the old age population, and thus contributing to the increase in number of people suffering from neurodegenerative diseases. Economically it is of a great burden to society and the affected family. No current treatment aims to replace, protect, and regenerate lost neurons; instead, it alleviates the symptoms, extends the life span by a few months and creates severe side effects. Moreover, people who are affected are physically dependent for performing their basic activities, which makes their life miserable. There is an urgent need for therapy that could be able to overcome the deficits of conventional therapy for neurodegenerative diseases. Stem cells, the unspecialized cells with the properties of self-renewing and potency to differentiate into various cells types can become a potent therapeutic option for neurodegenerative diseases. Stem cells have been widely used in clinical trials to evaluate their potential in curing different types of ailments. In this review, we discuss the various types of stem cells and their potential use in the treatment of neurodegenerative disease based on published preclinical and clinical studies.
Collapse
Affiliation(s)
- Aishwarya L
- Department of Biomedical Sciences, Sri Ramachandra Institute of Higher Education and Research, Chennai-600 116. India
| | - Dharmarajan Arun
- Department of Biomedical Sciences, Sri Ramachandra Institute of Higher Education and Research, Chennai-600 116. India
| | - Suresh Kannan
- Department of Biomedical Sciences, Sri Ramachandra Institute of Higher Education and Research, Chennai-600 116. India
| |
Collapse
|
|
29
|
Yang C, Qi Y, Sun Z. The Role of Sonic Hedgehog Pathway in the Development of the Central Nervous System and Aging-Related Neurodegenerative Diseases. Front Mol Biosci 2021; 8:711710. [PMID: 34307464 PMCID: PMC8295685 DOI: 10.3389/fmolb.2021.711710] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 06/10/2021] [Indexed: 01/09/2023] Open
Abstract
The Sonic hedgehog (SHH) pathway affects neurogenesis and neural patterning during the development of the central nervous system. Dysregulation of the SHH pathway in the brain contributes to aging-related neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. At present, the SHH signaling pathway can be divided into the canonical signaling pathway and non-canonical signaling pathway, which directly or indirectly mediates other related pathways involved in the development of neurodegenerative diseases. Hence, an in-depth knowledge of the SHH signaling pathway may open an avenue of possibilities for the treatment of neurodegenerative diseases. Here, we summarize the role and mechanism of the SHH signaling pathway in the development of the central nervous system and aging-related neurodegenerative diseases. In this review, we will also highlight the potential of the SHH pathway as a therapeutic target for treating neurodegenerative diseases.
Collapse
Affiliation(s)
- Chen Yang
- Department of Neurology, The Second Affiliated Hospital of Shanxi Medical University, Taiyuan, China
| | - Yan Qi
- Department of Neurology, The Second Affiliated Hospital of Shanxi Medical University, Taiyuan, China
| | - Zhitang Sun
- Department of Neurology, The Second Affiliated Hospital of Shanxi Medical University, Taiyuan, China
| |
Collapse
|
|
30
|
Ornelas-González A, González-González M, Rito-Palomares M. Microcarrier-based stem cell bioprocessing: GMP-grade culture challenges and future trends for regenerative medicine. Crit Rev Biotechnol 2021; 41:1081-1095. [PMID: 33730936 DOI: 10.1080/07388551.2021.1898328] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Recently, stem cell-based therapies have been proposed as an alternative for the treatment of many diseases. Stem cells (SCs) are well known for their capacity to preserve themselves, proliferate, and differentiate into multiple lineages. These characteristics allow stem cells to be a viable option for the treatment of diverse diseases. Traditional methodologies based on 2-dimensional culture techniques (T-flasks and Petri dishes) are simple and well standardized; however, they present disadvantages that limit the production of the cell yield required for regenerative medicine applications. Lately, microcarrier (MC)-based culture techniques have emerged as an attractive platform for expanding stem cells in suspension systems. Although the use of stem cell expansion on MCs has recently shown significant increase, their implementation for medical purposes is been hampered by bottlenecks in upstream and downstream processing. Therefore, there is an urgent need in the development of bioprocesses that simplify stem cell cultures under xeno-free conditions and detachment from MCs without diminishing their pluripotency and viability. A critical analysis of the factors that impact the up and downstream bioprocessing on MC-based stem cell cultures is presented in this review. This analysis aims to raise the awareness of the current drawbacks that limit MC-based stem cell bioprocessing in regenerative medicine and propose alternatives to overcome them.
Collapse
Affiliation(s)
| | | | - Marco Rito-Palomares
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Mexico
| |
Collapse
|
|
31
|
Ahani-Nahayati M, Shariati A, Mahmoodi M, Olegovna Zekiy A, Javidi K, Shamlou S, Mousakhani A, Zamani M, Hassanzadeh A. Stem cell in neurodegenerative disorders; an emerging strategy. Int J Dev Neurosci 2021; 81:291-311. [PMID: 33650716 DOI: 10.1002/jdn.10101] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 02/13/2021] [Accepted: 02/24/2021] [Indexed: 01/28/2023] Open
Abstract
Neurodegenerative disorders are a diversity of disorders, surrounding Alzheimer's (AD), Parkinson's (PD), Huntington's diseases (HD), and amyotrophic lateral sclerosis (ALS) accompanied by some other less common diseases generally characterized by either developed deterioration of central or peripheral nervous system structurally or functionally. Today, with the viewpoint of an increasingly aging society, the number of patients with neurodegenerative diseases and sociomedical burdens will spread intensely. During the last decade, stem cell technology has attracted great attention for treating neurodegenerative diseases worldwide because of its unique attributes. As acknowledged, there are several categories of stem cells being able to proliferate and differentiate into various cellular lineages, highlighting their significance in the context of regenerative medicine. In preclinical models, stem cell therapy using mesenchymal stem/stromal cells (MSCs), hematopoietic stem cells (HSCs), and neural progenitor or stem cells (NPCs or NSCs) along with pluripotent stem cells (PSCs)-derived neuronal cells could elicit desired therapeutic effects, enabling functional deficit rescue partially. Regardless of the noteworthy progress in our scientific awareness and understanding of stem cell biology, there still exist various challenges to defeat. In the present review, we provide a summary of the therapeutic potential of stem cells and discuss the current status and prospect of stem cell strategy in neurodegenerative diseases, in particular, AD, PD, ALS, and HD.
Collapse
Affiliation(s)
- Milad Ahani-Nahayati
- Department of Tissue Engineering and Applied Cell Science, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Ali Shariati
- Stem Cell Research Center, Tehran University of Medical Science, Tehran, Iran
| | - Mahnaz Mahmoodi
- Department of Biology, School of Basic Science, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Angelina Olegovna Zekiy
- Department of Prosthetic Dentistry, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Kamran Javidi
- School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.,Immunology Research Center (IRC), Tabriz University of Medical Sciences, Tabriz, Iran
| | - Somayeh Shamlou
- Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Akbar Mousakhani
- Department of Plant Sciences, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Majid Zamani
- Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Ali Hassanzadeh
- Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Neurosciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
32
|
Ford E, Pearlman J, Ruan T, Manion J, Waller M, Neely GG, Caron L. Human Pluripotent Stem Cells-Based Therapies for Neurodegenerative Diseases: Current Status and Challenges. Cells 2020; 9:E2517. [PMID: 33233861 PMCID: PMC7699962 DOI: 10.3390/cells9112517] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Revised: 11/13/2020] [Accepted: 11/17/2020] [Indexed: 12/11/2022] Open
Abstract
Neurodegenerative diseases are characterized by irreversible cell damage, loss of neuronal cells and limited regeneration potential of the adult nervous system. Pluripotent stem cells are capable of differentiating into the multitude of cell types that compose the central and peripheral nervous systems and so have become the major focus of cell replacement therapies for the treatment of neurological disorders. Human embryonic stem cell (hESC) and human induced pluripotent stem cell (hiPSC)-derived cells have both been extensively studied as cell therapies in a wide range of neurodegenerative disease models in rodents and non-human primates, including Parkinson's disease, stroke, epilepsy, spinal cord injury, Alzheimer's disease, multiple sclerosis and pain. In this review, we discuss the latest progress made with stem cell therapies targeting these pathologies. We also evaluate the challenges in clinical application of human pluripotent stem cell (hPSC)-based therapies including risk of oncogenesis and tumor formation, immune rejection and difficulty in regeneration of the heterogeneous cell types composing the central nervous system.
Collapse
Affiliation(s)
- Elizabeth Ford
- Dr. John and Anne Chong Lab for Functional Genomics, Charles Perkins Centre, Centenary Institute, University of Sydney, Camperdown, NSW 2006, Australia; (E.F.); (J.P.); (T.R.); (J.M.); (M.W.); (G.G.N.)
- School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW 2006, Australia
- Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
| | - Jodie Pearlman
- Dr. John and Anne Chong Lab for Functional Genomics, Charles Perkins Centre, Centenary Institute, University of Sydney, Camperdown, NSW 2006, Australia; (E.F.); (J.P.); (T.R.); (J.M.); (M.W.); (G.G.N.)
- School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW 2006, Australia
- Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
| | - Travis Ruan
- Dr. John and Anne Chong Lab for Functional Genomics, Charles Perkins Centre, Centenary Institute, University of Sydney, Camperdown, NSW 2006, Australia; (E.F.); (J.P.); (T.R.); (J.M.); (M.W.); (G.G.N.)
- School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW 2006, Australia
| | - John Manion
- Dr. John and Anne Chong Lab for Functional Genomics, Charles Perkins Centre, Centenary Institute, University of Sydney, Camperdown, NSW 2006, Australia; (E.F.); (J.P.); (T.R.); (J.M.); (M.W.); (G.G.N.)
- School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW 2006, Australia
- Department of Urology, Boston Children’s Hospital, Boston, MA 02115, USA
- Departments of Surgery and Microbiology, Harvard Medical School, Boston, MA 02115, USA
| | - Matthew Waller
- Dr. John and Anne Chong Lab for Functional Genomics, Charles Perkins Centre, Centenary Institute, University of Sydney, Camperdown, NSW 2006, Australia; (E.F.); (J.P.); (T.R.); (J.M.); (M.W.); (G.G.N.)
- School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW 2006, Australia
| | - Gregory G. Neely
- Dr. John and Anne Chong Lab for Functional Genomics, Charles Perkins Centre, Centenary Institute, University of Sydney, Camperdown, NSW 2006, Australia; (E.F.); (J.P.); (T.R.); (J.M.); (M.W.); (G.G.N.)
- School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW 2006, Australia
| | - Leslie Caron
- Dr. John and Anne Chong Lab for Functional Genomics, Charles Perkins Centre, Centenary Institute, University of Sydney, Camperdown, NSW 2006, Australia; (E.F.); (J.P.); (T.R.); (J.M.); (M.W.); (G.G.N.)
- School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW 2006, Australia
| |
Collapse
|
|
33
|
Jia N, Chong J, Sun L. Application of stem cell biology in treating neurodegenerative diseases. Int J Neurosci 2020; 132:815-825. [PMID: 33081549 DOI: 10.1080/00207454.2020.1840376] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
BACKGROUND The appropriate strategies are needed for stimulating the endogenous neurogenesis or introducing extrinsic neural progenitors, which could be harnessed as the regenerative resources for cueing the neurodegenerations. Adult neurogenesis is the endogenous continuing physiology in limited brain regions such as hippocampus, olfactory system, and hypothalamus. Besides adult neurogenesis, induced pluripotent stem cells (iPSCs) induced functional neurons could be another option for regenerative therapies. OBJECTIVE Current studies are trying to improve the adult neurogenesis and enable the iPSCs induced neurons into neural regeneration. Methods: Here in this review, we mainly introduced the recent progress in neural stem cell biology and its application in the treatment of the neurodegenerations. We main separated the strategy in summarizing the mediators and potential targets to promoting endogenous neural regeneration and transplantation of neural progenitors. CONCLUSION By collecting and comparing the advantages disadvantages between above-mentioned two strategies, we will offer the insight on future development of stem cell therapy in treating neurodegenerative patients.
Collapse
Affiliation(s)
- Na Jia
- Beijing University of Posts and Telecommunications, Beijing, China
| | - Jingping Chong
- Beijing University of Posts and Telecommunications, Beijing, China.,Shanghai University of Engineering Science, Shanghai, China
| | - Lina Sun
- Beijing University of Posts and Telecommunications, Beijing, China.,College of PE and Sport, Beijing Normal University, Beijing, China
| |
Collapse
|
|
34
|
Kim J, Lee Y, Lee S, Kim K, Song M, Lee J. Mesenchymal Stem Cell Therapy and Alzheimer's Disease: Current Status and Future Perspectives. J Alzheimers Dis 2020; 77:1-14. [PMID: 32741816 DOI: 10.3233/jad-200219] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Alzheimer's disease (AD) is the most common progressive neurodegenerative disease worldwide, but its cause remains unclear. Although a few drugs can provide temporary and partial relief of symptoms in some patients, no curative treatment is available. Therefore, attention has been focused on research using stem cells to treat AD. Among stem cells, mesenchymal stem cells (MSCs) have been used to treat the related pathologies in animal models of AD, and other neurodegenerative disease. This review describes latest research trends on the use of MSC-based therapies in AD and its action of mechanism. MSCs have several beneficial effects. They would be specified as the reduction of neuroinflammation, the elimination of amyloid-β, neurofibrillary tangles, and abnormal protein degradation, the promotion of autophagy-associated and blood-brain barrier recoveries, the upregulation of acetylcholine levels, improved cognition, and the recovery of mitochondrial transport. Therefore, this review describes the latest research trends in MSC-based therapy for AD by demonstrating the importance of MSC-based therapy and understanding of its mechanisms in AD and discusses the limitations and perspectives of stem cell therapy in AD.
Collapse
Affiliation(s)
- Jieun Kim
- Department of Pharmacy, College of Pharmacy, Pusan National University, Busan, Republic of Korea
| | - Yujeong Lee
- Department of Pharmacy, College of Pharmacy, Pusan National University, Busan, Republic of Korea.,Cognitive Science Research Group, Korea Brain Research Institute, Daegu, Republic of Korea
| | - Seulah Lee
- Department of Pharmacy, College of Pharmacy, Pusan National University, Busan, Republic of Korea
| | - Kipom Kim
- Brain Research Core Facilities, Korea Brain Research Institute, Daegu, Republic of Korea
| | - Minjung Song
- Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit, Wellcome Trust - Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, UK
| | - Jaewon Lee
- Department of Pharmacy, College of Pharmacy, Pusan National University, Busan, Republic of Korea
| |
Collapse
|
|
35
|
Liu XY, Yang LP, Zhao L. Stem cell therapy for Alzheimer's disease. World J Stem Cells 2020; 12:787-802. [PMID: 32952859 PMCID: PMC7477654 DOI: 10.4252/wjsc.v12.i8.787] [Citation(s) in RCA: 92] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 04/10/2020] [Accepted: 07/26/2020] [Indexed: 02/07/2023] Open
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory loss and cognitive impairment. It is caused by synaptic failure and excessive accumulation of misfolded proteins. To date, almost all advanced clinical trials on specific AD-related pathways have failed mostly due to a large number of neurons lost in the brain of patients with AD. Also, currently available drug candidates intervene too late. Stem cells have improved characteristics of self-renewal, proliferation, differentiation, and recombination with the advent of stem cell technology and the transformation of these cells into different types of central nervous system neurons and glial cells. Stem cell treatment has been successful in AD animal models. Recent preclinical studies on stem cell therapy for AD have proved to be promising. Cell replacement therapies, such as human embryonic stem cells or induced pluripotent stem cell-derived neural cells, have the potential to treat patients with AD, and human clinical trials are ongoing in this regard. However, many steps still need to be taken before stem cell therapy becomes a clinically feasible treatment for human AD and related diseases. This paper reviews the pathophysiology of AD and the application prospects of related stem cells based on cell type.
Collapse
Affiliation(s)
- Xin-Yu Liu
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China
| | - Lin-Po Yang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China
| | - Lan Zhao
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China
- Tianjin Key Laboratory of Acupuncture and Moxibustion, Tianjin 300381, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300381, China.
| |
Collapse
|
|
36
|
Zhang L, Dong ZF, Zhang JY. Immunomodulatory role of mesenchymal stem cells in Alzheimer's disease. Life Sci 2020; 246:117405. [PMID: 32035129 DOI: 10.1016/j.lfs.2020.117405] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 02/03/2020] [Accepted: 02/04/2020] [Indexed: 02/06/2023]
Abstract
Alzheimer's disease (AD) is one of the most common causes of dementia and is characterized by gradual loss in memory, language, and cognitive function. The hallmarks of AD include extracellular amyloid deposition, intracellular neuronal fiber entanglement, and neuronal loss. Despite strenuous efforts toward improvement of AD, there remains a lack of effective treatment and current pharmaceutical therapies only alleviate the symptoms for a short period of time. Interestingly, some progress has been achieved in treatment of AD based on mesenchymal stem cell (MSC) transplantation in recent years. MSC transplantation, as a rising therapy, is used as an intervention in AD, because of the enormous potential of MSCs, including differentiation potency, immunoregulatory function, and no immunological rejection. Although numerous strategies have focused on the use of MSCs to replace apoptotic or degenerating neurons, recent studies have implied that MSC-immunoregulation, which modulates the activity state of microglia or astrocytes and mediates neuroinflammation via several transcription factors (NFs) signaling pathways, may act as a major mechanism for the therapeutic efficacy of MSC and be responsible for some of the satisfactory results. In this review, we will focus on the role of MSC-immunoregulation in MSC-based therapy for AD.
Collapse
Affiliation(s)
- Lu Zhang
- Department of Pediatric Research Institute, Ministry of Education Key Laboratory of Child Development and Disorders, National Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, China.
| | - Zhi-Fang Dong
- Department of Pediatric Research Institute, Ministry of Education Key Laboratory of Child Development and Disorders, National Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, China.
| | - Jie-Yuan Zhang
- Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China.
| |
Collapse
|
|
37
|
Abstract
Alzheimer's disease (AD) is the most common neurodegenerative disease caused by eventually aggregated amyloid β (Aβ) plaques in degenerating neurons of the aging brain. These aggregated protein plaques mainly consist of Aβ fibrils and neurofibrillary tangles (NFTs) of phosphorylated tau protein. Even though some cholinesterase inhibitors, NMDA receptor antagonist, and monoclonal antibodies were developed to inhibit neurodegeneration or activate neural regeneration or clear off the Aβ deposits, none of the treatment is effective in improving the cognitive and memory dysfunctions of the AD patients. Thus, stem cell therapy represents a powerful tool for the treatment of AD. In addition to discussing the advents in molecular pathogenesis and animal models of this disease and the treatment approaches using small molecules and immunoglobulins against AD, we will focus on the stem cell sources for AD using neural stem cells (NSCs); embryonic stem cells (ESCs); and mesenchymal stem cells (MSCs) from bone marrow, umbilical cord, and umbilical cord blood. In particular, patient-specific-induced pluripotent stem cells (iPS cells) are proposed as a future prospective and the challenges for the treatment of AD.
Collapse
|
|
38
|
Zhang T, Ke W, Zhou X, Qian Y, Feng S, Wang R, Cui G, Tao R, Guo W, Duan Y, Zhang X, Cao X, Shu Y, Yue C, Jing N. Human Neural Stem Cells Reinforce Hippocampal Synaptic Network and Rescue Cognitive Deficits in a Mouse Model of Alzheimer's Disease. Stem Cell Reports 2019; 13:1022-1037. [PMID: 31761676 PMCID: PMC6915849 DOI: 10.1016/j.stemcr.2019.10.012] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Revised: 10/21/2019] [Accepted: 10/23/2019] [Indexed: 12/26/2022] Open
Abstract
Alzheimer's disease (AD) is characterized by memory impairments in its earliest clinical phase. The synaptic loss and dysfunction leading to failures of synaptic networks in AD brain directly cause cognitive deficits of patient. However, it remains unclear whether the synaptic networks in AD brain could be repaired. In this study, we generated functional human induced neural progenitor/stem cells (iNPCs) that had been transplanted into the hippocampus of immunodeficient wild-type and AD mice. The grafted human iNPCs efficiently differentiated into neurons that displayed long-term survival, progressively acquired mature membrane properties, formed graft-host synaptic connections with mouse neurons and functionally integrated into local synaptic circuits, which eventually reinforced and repaired the neural networks of host hippocampus. Consequently, AD mice with human iNPCs exhibited enhanced synaptic plasticity and improved cognitive abilities. Together, our results suggest that restoring synaptic failures by stem cells might provide new directions for the development of novel treatments for human AD.
Collapse
Affiliation(s)
- Ting Zhang
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China
| | - Wei Ke
- State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, 19 Xinjiekou Wai Street, Beijing 100875, China
| | - Xuan Zhou
- Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai, China
| | - Yun Qian
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China
| | - Su Feng
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China
| | - Ran Wang
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China
| | - Guizhong Cui
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China
| | - Ran Tao
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China
| | - Wenke Guo
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
| | - Yanhong Duan
- Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai, China
| | - Xiaobing Zhang
- Division of Regenerative Medicine, Department of Medicine, Loma Linda University, Loma Linda, CA, 92350, USA
| | - Xiaohua Cao
- Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai, China
| | - Yousheng Shu
- State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, 19 Xinjiekou Wai Street, Beijing 100875, China
| | - Chunmei Yue
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
| | - Naihe Jing
- State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China.
| |
Collapse
|
|
39
|
Boese AC, Hamblin MH, Lee JP. Neural stem cell therapy for neurovascular injury in Alzheimer's disease. Exp Neurol 2019; 324:113112. [PMID: 31730762 DOI: 10.1016/j.expneurol.2019.113112] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Revised: 11/02/2019] [Accepted: 11/11/2019] [Indexed: 02/07/2023]
Abstract
Alzheimer's disease (AD), the most common form of dementia, is characterized by progressive neurodegeneration leading to severe cognitive decline and eventual death. AD pathophysiology is complex, but neurotoxic accumulation of amyloid-β (Aβ) and hyperphosphorylation of Tau are believed to be main drivers of neurodegeneration in AD. The formation and deposition of Aβ plaques occurs in the brain parenchyma as well as in the cerebral vasculature. Thus, proper blood-brain barrier (BBB) and cerebrovascular functioning are crucial for clearance of Aβ from the brain, and neurovascular dysfunction may be a critical component of AD development. Further, neuroinflammation and dysfunction of angiogenesis, neurogenesis, and neurorestorative capabilities play a role in AD pathophysiology. Currently, there is no effective treatment to prevent or restore loss of brain tissue and cognitive decline in patients with AD. Based on multifactorial and complex pathophysiological cascades in multiple Alzheimer's disease stages, effective AD therapies need to focus on targeting early AD pathology and preserving cerebrovascular function. Neural stem cells (NSCs) participate extensively in mammalian brain homeostasis and repair and exhibit pleiotropic intrinsic properties that likely make them attractive candidates for the treatment of AD. In the review, we summarize the current advances in knowledge regarding neurovascular aspects of AD-related neurodegeneration and discuss multiple actions of NSCs from preclinical studies of AD to evaluate their potential for future clinical treatment of AD.
Collapse
Affiliation(s)
- Austin C Boese
- Department of Physiology, Tulane University School of Medicine, New Orleans, LA 70112, USA
| | - Milton H Hamblin
- Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA
| | - Jean-Pyo Lee
- Department of Physiology, Tulane University School of Medicine, New Orleans, LA 70112, USA; Tulane Brain Institute, Tulane University, New Orleans, LA 70112, USA.
| |
Collapse
|
|
40
|
Barrett MJ, Cloud LJ, Shah H, Holloway KL. Therapeutic approaches to cholinergic deficiency in Lewy body diseases. Expert Rev Neurother 2019; 20:41-53. [DOI: 10.1080/14737175.2020.1676152] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Affiliation(s)
- Matthew J. Barrett
- Department of Neurology, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Leslie J. Cloud
- Department of Neurology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
| | - Harsh Shah
- Department of Neurosurgery, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
| | - Kathryn L. Holloway
- Department of Neurosurgery, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
- The Southeast Parkinson’s Disease Research, Education, and Care Center, Hunter Holmes McGuire Veteran Affairs Medical Center, Richmond, VA, USA
| |
Collapse
|
|
41
|
Neurodegeneration and Neuro-Regeneration-Alzheimer's Disease and Stem Cell Therapy. Int J Mol Sci 2019; 20:ijms20174272. [PMID: 31480448 PMCID: PMC6747457 DOI: 10.3390/ijms20174272] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Revised: 08/27/2019] [Accepted: 08/28/2019] [Indexed: 12/17/2022] Open
Abstract
Aging causes many changes in the human body, and is a high risk for various diseases. Dementia, a common age-related disease, is a clinical disorder triggered by neurodegeneration. Brain damage caused by neuronal death leads to cognitive decline, memory loss, learning inabilities and mood changes. Numerous disease conditions may cause dementia; however, the most common one is Alzheimer’s disease (AD), a futile and yet untreatable illness. Adult neurogenesis carries the potential of brain self-repair by an endogenous formation of newly-born neurons in the adult brain; however it also declines with age. Strategies to improve the symptoms of aging and age-related diseases have included different means to stimulate neurogenesis, both pharmacologically and naturally. Finally, the regulatory mechanisms of stem cells neurogenesis or a functional integration of newborn neurons have been explored to provide the basis for grafted stem cell therapy. This review aims to provide an overview of AD pathology of different neural and glial cell types and summarizes current strategies of experimental stem cell treatments and their putative future use in clinical settings.
Collapse
|
|
42
|
Reddy AP, Ravichandran J, Carkaci-Salli N. Neural regeneration therapies for Alzheimer's and Parkinson's disease-related disorders. Biochim Biophys Acta Mol Basis Dis 2019; 1866:165506. [PMID: 31276770 DOI: 10.1016/j.bbadis.2019.06.020] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Revised: 06/24/2019] [Accepted: 06/26/2019] [Indexed: 12/20/2022]
Abstract
Neurodegenerative diseases are devastating mental illnesses without a cure. Alzheimer's disease (AD) characterized by memory loss, multiple cognitive impairments, and changes in personality and behavior. Although tremendous progress has made in understanding the basic biology in disease processes in AD and PD, we still do not have early detectable biomarkers for these diseases. Just in the United States alone, federal and nonfederal funding agencies have spent billions of dollars on clinical trials aimed at finding drugs, but we still do not have a drug or an agent that can slow the AD or PD disease process. One primary reason for this disappointing result may be that the clinical trials enroll patients with AD or PD at advances stages. Although many drugs and agents are tested preclinical and are promising, in human clinical trials, they are mostly ineffective in slowing disease progression. One therapy that has been promising is 'stem cell therapy' based on cell culture and pre-clinical studies. In the few clinical studies that have investigated therapies in clinical trials with AD and PD patients at stage I. The therapies, such as stem cell transplantation - appear to delay the symptoms in AD and PD. The purpose of this article is to describe clinical trials using 1) stem cell transplantation methods in AD and PD mouse models and 2) regenerative medicine in AD and PD mouse models, and 3) the current status of investigating preclinical stem cell transplantation in patients with AD and PD.
Collapse
Affiliation(s)
- Arubala P Reddy
- Pharmacology & Neuroscience Department, Texas Tech University Health Sciences Center, 3601 4th Street, MS 9424, Lubbock, TX 79430, United States.
| | - Janani Ravichandran
- Texas Tech University Health Sciences Center El Paso, 5001 El Paso Drive, El Paso, TX 79905, United States.
| | - Nurgul Carkaci-Salli
- Department of Pharmacology, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033.
| |
Collapse
|
|
43
|
Chakari-Khiavi F, Dolati S, Chakari-Khiavi A, Abbaszadeh H, Aghebati-Maleki L, Pourlak T, Mehdizadeh A, Yousefi M. Prospects for the application of mesenchymal stem cells in Alzheimer's disease treatment. Life Sci 2019; 231:116564. [PMID: 31202840 DOI: 10.1016/j.lfs.2019.116564] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2019] [Revised: 06/11/2019] [Accepted: 06/11/2019] [Indexed: 01/09/2023]
Abstract
Alzheimer's disease (AD) as a dementia and neurodegenerative disease, is mostly prevalent among people more than 65 years. AD is mostly manifested in the form of degraded mental function, such as losing memory and impaired cognitive function. Due to inefficiency of traditional pharmacological therapeutic approaches with no long-term cure, cell therapy can be considered as a capable approach in AD management. Therapies based on mesenchymal stem cells (MSCs) have provided hopeful results in experimental models regarding several disorders. MSCs enhance the levels of functional recoveries in pathologic experimental models of central nervous system (CNS) and are being investigated in clinical trials in neurological disorders. However, there is limited knowledge on the protective capabilities of MSCs in AD management. Almost, several experiments have suggested positive effects of MSCs and helped to better understand of AD-related dementia mechanism. MSCs have the potential to be used in AD treatment through amyloid-β peptide (AB), Tau protein and cholinergic system. This review aimed to clarify the promising perspective of MSCs in the context of AD.
Collapse
Affiliation(s)
- Forough Chakari-Khiavi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Pharmaceutical Chemistry, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sanam Dolati
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Aging Research Institute, Tabriz University of Medical Sciences Tabriz, Iran
| | - Aref Chakari-Khiavi
- Aging Research Institute, Tabriz University of Medical Sciences Tabriz, Iran
| | - Hossein Abbaszadeh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Tannaz Pourlak
- Aging Research Institute, Tabriz University of Medical Sciences Tabriz, Iran
| | - Amir Mehdizadeh
- Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehdi Yousefi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Aging Research Institute, Tabriz University of Medical Sciences Tabriz, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran..
| |
Collapse
|
|
44
|
Abstract
In recent years, stem cell therapy has become a very promising and advanced scientific research topic. The development of treatment methods has evoked great expectations. This paper is a review focused on the discovery of different stem cells and the potential therapies based on these cells. The genesis of stem cells is followed by laboratory steps of controlled stem cell culturing and derivation. Quality control and teratoma formation assays are important procedures in assessing the properties of the stem cells tested. Derivation methods and the utilization of culturing media are crucial to set proper environmental conditions for controlled differentiation. Among many types of stem tissue applications, the use of graphene scaffolds and the potential of extracellular vesicle-based therapies require attention due to their versatility. The review is summarized by challenges that stem cell therapy must overcome to be accepted worldwide. A wide variety of possibilities makes this cutting edge therapy a turning point in modern medicine, providing hope for untreatable diseases.
Collapse
Affiliation(s)
- Wojciech Zakrzewski
- Department of Experimental Surgery and Biomaterials Research, Wroclaw Medical University, Bujwida 44, Wrocław, 50-345 Poland
| | - Maciej Dobrzyński
- Department of Conservative Dentistry and Pedodontics, Krakowska 26, Wrocław, 50-425 Poland
| | - Maria Szymonowicz
- Department of Experimental Surgery and Biomaterials Research, Wroclaw Medical University, Bujwida 44, Wrocław, 50-345 Poland
| | - Zbigniew Rybak
- Department of Experimental Surgery and Biomaterials Research, Wroclaw Medical University, Bujwida 44, Wrocław, 50-345 Poland
| |
Collapse
|
|
45
|
Alipour M, Nabavi SM, Arab L, Vosough M, Pakdaman H, Ehsani E, Shahpasand K. Stem cell therapy in Alzheimer's disease: possible benefits and limiting drawbacks. Mol Biol Rep 2018; 46:1425-1446. [PMID: 30565076 DOI: 10.1007/s11033-018-4499-7] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2018] [Accepted: 11/13/2018] [Indexed: 02/06/2023]
Abstract
Alzheimer's disease (AD) is the sixth leading cause of death globally and the main reason for dementia in elderly people. AD is a long-term and progressive neurodegenerative disorder that steadily worsens memory and communicating skills eventually leads to a disabled person of performing simple daily tasks. Unfortunately, numerous clinical trials exploring new therapeutic drugs have encountered disappointing outcomes in terms of improved cognitive performance since they are not capable of halting or stimulating the regeneration of already-damaged neural cells, and merely provide symptomatic relief. Therefore, a deeper understanding of the mechanism of action of stem cell may contribute to the development of novel and effective therapies. The revolutionary discovery of stem cells has cast a new hope for the development of disease-modifying treatments for AD, in terms of their potency in the replenishment of lost cells via differentiating towards specific lineages, stimulating in situ neurogenesis, and delivering the therapeutic agents to the brain. Herein, firstly, we explore the pathophysiology of AD. Next, we summarize the most recent preclinical stem cell reports designed for AD treatment, their benefits and outcomes according to cell type. We briefly review relevant clinical trials and their potential clinical applications in order to find a unique solution to effectively relieve the patients' pain.
Collapse
Affiliation(s)
- Masoume Alipour
- Department of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Banihashem Sq., Banihashem St., Resalat highway, P.O. Box 19395-4644, Tehran, Iran
| | - Seyed Massood Nabavi
- Department of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Banihashem Sq., Banihashem St., Resalat highway, P.O. Box 19395-4644, Tehran, Iran
| | - Leila Arab
- Department of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Banihashem Sq., Banihashem St., Resalat highway, P.O. Box 19395-4644, Tehran, Iran
| | - Massoud Vosough
- Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Hossein Pakdaman
- Department of Neurology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ehsan Ehsani
- Department of Biology, Roudehen Branch, Islamic Azad University, Roudehen, Iran
| | - Koorosh Shahpasand
- Department of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Banihashem Sq., Banihashem St., Resalat highway, P.O. Box 19395-4644, Tehran, Iran.
| |
Collapse
|
|
46
|
Duru LN, Quan Z, Qazi TJ, Qing H. Stem cells technology: a powerful tool behind new brain treatments. Drug Deliv Transl Res 2018; 8:1564-1591. [PMID: 29916013 DOI: 10.1007/s13346-018-0548-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Stem cell research has recently become a hot research topic in biomedical research due to the foreseen unlimited potential of stem cells in tissue engineering and regenerative medicine. For many years, medicine has been facing intense challenges, such as an insufficient number of organ donations that is preventing clinicians to fulfill the increasing needs. To try and overcome this regrettable matter, research has been aiming at developing strategies to facilitate the in vitro culture and study of stem cells as a tool for tissue regeneration. Meanwhile, new developments in the microfluidics technology brought forward emerging cell culture applications that are currently allowing for a better chemical and physical control of cellular microenvironment. This review presents the latest developments in stem cell research that brought new therapies to the clinics and how the convergence of the microfluidics technology with stem cell research can have positive outcomes on the fields of regenerative medicine and high-throughput screening. These advances will bring new translational solutions for drug discovery and will upgrade in vitro cell culture to a new level of accuracy and performance. We hope this review will provide new insights into the understanding of new brain treatments from the perspective of stem cell technology especially regarding regenerative medicine and tissue engineering.
Collapse
Affiliation(s)
- Lucienne N Duru
- School of Life Science, Beijing Institute of Technology, Beijing, China
| | - Zhenzhen Quan
- School of Life Science, Beijing Institute of Technology, Beijing, China
| | - Talal Jamil Qazi
- School of Life Science, Beijing Institute of Technology, Beijing, China
| | - Hong Qing
- School of Life Science, Beijing Institute of Technology, Beijing, China. .,Beijing Key Laboratory of Separation and Analysis in Biomedical and Pharmaceuticals, Department of Biomedical Engineering, School of Life Science, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing, 100081, China.
| |
Collapse
|
|
47
|
Hosseini SA, Mohammadi R, Noruzi S, Mohamadi Y, Azizian M, Mousavy SM, Ghasemi F, Hesari A, Sahebkar A, Salarinia R, Aghdam AM, Mirzaei H. Stem cell- and gene-based therapies as potential candidates in Alzheimer's therapy. J Cell Biochem 2018; 119:8723-8736. [PMID: 30074262 DOI: 10.1002/jcb.27202] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2018] [Accepted: 05/24/2018] [Indexed: 12/11/2022]
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder, which is associated with impairments of memory, thinking, language, and reasoning. Despite extensive research aiming at the treatment of AD, durable and complete remissions are rare. Hence, new therapeutic approaches are required. Among various therapeutic approaches, stem cells (ie, neural stem cells, mesenchymal stem cells, and embryonic stem cells) and delivery of protective genes such as encoding nerve growth factor, APOE, and glial cell-derived neurotrophic factor have generated promise in AD therapy. Here, we summarized a variety of effective therapeutic approaches (ie, stem cells, and genes) in AD therapy.
Collapse
Affiliation(s)
- Seyede Atefe Hosseini
- Department of Medical Biotechnology and Molecular Sciences, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Rezvan Mohammadi
- Department of Medical Biotechnology and Molecular Sciences, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Somaye Noruzi
- Department of Medical Biotechnology and Molecular Sciences, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Yousef Mohamadi
- Department of Anatomy, Faculty of medicine, Tehran university of medical sciences, Tehran, Iran; Department of Anatomy, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
| | - Mitra Azizian
- Department of Clinical Biochemistry, Faculty of Medicine, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Seyed Mojta Mousavy
- Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Faezeh Ghasemi
- Department of Biotechnology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran
| | - AmirReza Hesari
- Department of Biotechnology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran.,School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Reza Salarinia
- Department of Medical Biotechnology and Molecular Sciences, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Arad Mobasher Aghdam
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamed Mirzaei
- Department of Biomaterials, Tissue Engineering and Nanotechnology, School of Advanced Technologies in Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| |
Collapse
|
|
48
|
Stem Cells as Potential Targets of Polyphenols in Multiple Sclerosis and Alzheimer's Disease. BIOMED RESEARCH INTERNATIONAL 2018; 2018:1483791. [PMID: 30112360 PMCID: PMC6077677 DOI: 10.1155/2018/1483791] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Accepted: 06/19/2018] [Indexed: 12/16/2022]
Abstract
Alzheimer's disease (AD) and multiple sclerosis are major neurodegenerative diseases, which are characterized by the accumulation of abnormal pathogenic proteins due to oxidative stress, mitochondrial dysfunction, impaired autophagy, and pathogens, leading to neurodegeneration and behavioral deficits. Herein, we reviewed the utility of plant polyphenols in regulating proliferation and differentiation of stem cells for inducing brain self-repair in AD and multiple sclerosis. Firstly, we discussed the genetic, physiological, and environmental factors involved in the pathophysiology of both the disorders. Next, we reviewed various stem cell therapies available and how they have proved useful in animal models of AD and multiple sclerosis. Lastly, we discussed how polyphenols utilize the potential of stem cells, either complementing their therapeutic effects or stimulating endogenous and exogenous neurogenesis, against these diseases. We suggest that polyphenols could be a potential candidate for stem cell therapy against neurodegenerative disorders.
Collapse
|
|
49
|
Kwak KA, Lee SP, Yang JY, Park YS. Current Perspectives regarding Stem Cell-Based Therapy for Alzheimer's Disease. Stem Cells Int 2018; 2018:6392986. [PMID: 29686714 PMCID: PMC5852851 DOI: 10.1155/2018/6392986] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2017] [Accepted: 01/15/2018] [Indexed: 02/07/2023] Open
Abstract
Alzheimer's disease (AD), a progressive neurodegenerative disorder featuring memory loss and cognitive impairment, is caused by synaptic failure and the excessive accumulation of misfolded proteins. Many unsuccessful attempts have been made to develop new small molecules or antibodies to intervene in the disease's pathogenesis. Stem cell-based therapies cast a new hope for AD treatment as a replacement or regeneration strategy. The results from recent preclinical studies regarding stem cell-based therapies are promising. Human clinical trials are now underway. However, a number of questions remain to be answered prior to safe and effective clinical translation. This review explores the pathophysiology of AD and summarizes the relevant stem cell research according to cell type. We also briefly summarize related clinical trials. Finally, future perspectives are discussed with regard to their clinical applications.
Collapse
Affiliation(s)
- Kyeong-Ah Kwak
- Department of Oral Anatomy, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea
| | - Seung-Pyo Lee
- Department of Oral Anatomy, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea
| | - Jin-Young Yang
- Department of Dental Hygiene, Daejeon Institute of Science and Technology, Daejeon, Republic of Korea
| | - Young-Seok Park
- Department of Oral Anatomy, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea
| |
Collapse
|
|
50
|
Kang JM, Yeon BK, Cho SJ, Suh YH. Stem Cell Therapy for Alzheimer's Disease: A Review of Recent Clinical Trials. J Alzheimers Dis 2018; 54:879-889. [PMID: 27567851 DOI: 10.3233/jad-160406] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Stem cell therapy has been noted to be a disease-modifying treatment for Alzheimer's disease (AD). After the failure to develop new drugs for AD, the number of studies on stem cells, such as mesenchymal stem cells (MSCs) and neural stem cells (NSCs), has increased from the early 2000 s. Issues pertaining to stem cells have been investigated in many animal studies in terms of stem cell origin, differentiation potency, method of culture, tumor formation, injection route, and mobility. Since 2010, mainly in East Asia, researchers began clinical trials investigating the use of stem cells for AD. Two phase I trials on moderate AD have been completed; though they revealed no severe acute or long-term side effects, no significant clinical efficacy was observed. Several studies, which involve more sophisticated study designs using different injection routes, well-established scales, and biomarkers such as amyloid positron emission tomography, are planned for mild to moderate AD patients. Here, we review the concept of stem cell therapy for AD and the progress of recent clinical trials.
Collapse
Affiliation(s)
- Jae Myeong Kang
- Department of Psychiatry, Gil Medical Center, Gachon University, College of Medicine, Incheon, Korea
| | - Byeong Kil Yeon
- Department of Psychiatry, Gil Medical Center, Gachon University, College of Medicine, Incheon, Korea.,Incheon Metropolitan Dementia Center, Incheon, Korea
| | - Seong-Jin Cho
- Department of Psychiatry, Gil Medical Center, Gachon University, College of Medicine, Incheon, Korea
| | - Yoo-Hun Suh
- Neuroscience Research Institute, Gachon University, College of Medicine, Incheon, Korea
| |
Collapse
|