scholarly journals Evading the Immune System: Immune Modulation and Immune Matching in Cell Replacement Therapies for Parkinson’s Disease

2021 ◽  
pp. 1-6
Author(s):  
Asuka Morizane ◽  
Jun Takahashi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Immune Modulation ◽  
Autologous Transplantation ◽  
Human Leukocyte ◽  
Allogeneic Transplantation ◽  
Leukocyte Antigen ◽  
The Brain

Stem cell-based therapies for Parkinson’s disease are now being applied clinically. Notably, studies have shown that controlling the graft-induced immune response improves the results. In this mini-review, we concisely summarize current approaches used for this control. We focus on four modes of stem cell-based therapies: autologous transplantation, allogeneic transplantation with human leukocyte antigen-matching and allogeneic transplantation without, and finally the application of “universal” pluripotent stem cells. We also discuss immuno-suppressive treatments and the monitoring of immune reactions in the brain.

scholarly journals Modeling the pathophysiology of Parkinson’s disease in patient-specific neurons

2020 ◽  
pp. 153537022096178
Author(s):  
Jian Feng
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Stem Cell ◽  
Basal Ganglia ◽  
Pluripotent Stem Cells ◽  
Patient Specific ◽  
Mechanistic Studies ◽  
Induced Pluripotent ◽  
Further Development

The 30 trillion cells that self-assemble into a human being originate from the pluripotent stem cells in the inner cell mass of a human blastocyst. The discovery of induced pluripotent stem cells (iPSCs) makes it possible to approximate various aspects of this natural developmental process artificially by generating materials that can be used in invasive mechanistic studies of virtually all human conditions. In Parkinson’s disease, instructions computed by the basal ganglia to control voluntary motor functions break down, leading to widespread rhythmic bursting activities in the basal ganglia and beyond. It is thought that these oscillatory neuronal activities, which disrupt aperiodic neurotransmission in a normal brain, may reduce information content in the instructions for motor control. Using midbrain neuronal cultures differentiated from iPSCs of Parkinson’s disease patients with parkin mutations, we find that parkin mutations cause oscillatory neuronal activities when dopamine D1-class receptors are activated. This system makes it possible to study the molecular basis of rhythmic bursting activities in Parkinson’s disease. Further development of stem cell models of Parkinson’s disease will enable better approximation of the situation in the brain of Parkinson’s disease patients. In this review, I will discuss what has been found in the past about the pathophysiology of motor dysfunction in Parkinson’s disease, especially oscillatory neuronal activities and how stem cell technologies may transform our abilities to understand the pathophysiology of Parkinson’s disease. Impact statement Research on the pathophysiology of Parkinson’s disease (PD) has generated effective therapies such as deep brain stimulation. A better understanding of PD pathophysiology calls for patient-specific materials amenable for invasive mechanistic studies. In this minireview, I discuss our recent work on oscillatory neuronal activities in midbrain neurons differentiated from induced pluripotent stem cells (iPSCs) of PD patients with parkin mutations. These patient-specific neurons enable a variety of studies previously not feasible in the human system. Further development in stem cell technologies may generate more realistic models for us to decipher PD pathophysiology. These new developments will transform research and development in Parkinson’s disease.

scholarly journals Allogeneic transplantation improves the overall and progression-free survival of Hodgkin lymphoma patients relapsing after autologous transplantation: a retrospective study based on the time of HLA typing and donor availability

Blood ◽  
2010 ◽  
Vol 115 (18) ◽  
pp. 3671-3677 ◽  
Author(s):  
Barbara Sarina ◽  
Luca Castagna ◽  
Lucia Farina ◽  
Francesca Patriarca ◽  
Fabio Benedetti ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Hodgkin Lymphoma ◽  
Autologous Transplantation ◽  
Multivariable Analysis ◽  
Human Leukocyte ◽  
Progression Free Survival ◽  
Allogeneic Transplantation ◽  
Hla Typing ◽  
Human Leukocyte Antigen Typing ◽  
Leukocyte Antigen

Abstract Hodgkin lymphoma relapsing after autologous transplantation (autoSCT) has a dismal outcome. Allogeneic transplantation (alloSCT) using reduced intensity conditioning (RIC) is a salvage option, but its effectiveness is still unclear. To evaluate the role of RIC alloSCT, we designed a retrospective study based on the commitment of attending physicians to perform a salvage alloSCT; thus, only Hodgkin lymphoma patients having human leukocyte antigen-typing immediately after the failed autoSCT were included. Of 185 patients, 122 found an identical sibling (55%), a matched unrelated (32%) or a haploidentical sibling (13%) donor; 63 patients did not find any donor. Clinical features of both groups did not differ. Two-year progression-free (PFS) and overall survival (OS) were better in the donor group (39.3% vs 14.2%, and 66% vs 42%, respectively, P < .001) with a median follow-up of 48 months. In multivariable analysis, having a donor was significant for better PFS and OS (P < .001). Patients allografted in complete remission showed a better PFS and OS. This is the largest study comparing RIC alloSCT versus conventional treatment after a failed autoSCT, indicating a survival benefit for patients having a donor.

scholarly journals Human leukocyte antigen variation and Parkinson’s disease

2011 ◽  
Vol 17 (5) ◽  
pp. 376-378 ◽  
Author(s):  
Andreas Puschmann ◽  
Christophe Verbeeck ◽  
Michael G. Heckman ◽  
Alexandra I. Soto-Ortolaza ◽  
Timothy Lynch ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Leukocyte Antigen

scholarly journals Immunogenetic Epidemiology of Dementia and Parkinson’s Disease in 14 Continental European Countries: Shared Human Leukocyte Antigen (HLA) Profiles

2021 ◽  
Vol 5 (2) ◽  
pp. 16-26
Author(s):  
Lisa M. James ◽  
Apostolos P. Georgopoulos
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Hla Class I ◽  
European Countries ◽  
Class I ◽  
Protective Mechanisms ◽  
Leukocyte Antigen ◽  
Epidemiology Of Dementia

Human leukocyte antigen (HLA), which is critically involved in immune response to foreign antigens and in autoimmunity, has been implicated in dementia and Parkinson’s disease. Here we report on the correlations between the population frequencies of 127 HLA Class I and II alleles and the population prevalence of dementia and Parkinson’s disease in 14 Continental Western European countries, extending previous work1,2. We used these correlations to construct and compare HLA profiles for each disease3. We found that (a) the HLA profiles of the two diseases were significantly correlated across both HLA Class I and Class II alleles, (b) negative (“protective”) HLA-disease correlations did not differ significantly for either HLA class, but (c) positive (“susceptibility”) HLA-disease correlations were significantly higher in dementia than in Parkinson’s disease for both HLA classes of alleles. These findings indicate that (a) dementia and Parkinson’s disease share immunogenetic HLA-related mechanisms, (b) HLA-related protective mechanisms (presumably against pathogens) do not differ between the two diseases, but (c) HLA-related susceptibility mechanisms (presumably underlying autoimmunity) are significantly stronger in dementia than in Parkinson’s disease.

scholarly journals Replacing what’s lost: a new era of stem cell therapy for Parkinson’s disease

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Yong Fan ◽  
Winanto ◽  
Shi-Yan Ng
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Stem Cell ◽  
Cell Therapy ◽  
Pluripotent Stem Cells ◽  
Cell Types ◽  
Cell Replacement Therapy ◽  
Safety And Efficacy ◽  
Cell Replacement

Abstract Background Stem cells hold tremendous promise for regenerative medicine because they can be expanded infinitely, giving rise to large numbers of differentiated cells required for transplantation. Stem cells can be derived from fetal sources, embryonic origins (embryonic stem cells or ESCs) or reprogrammed from adult cell types (induced pluripotent stem cells or iPSCs). One unique property of stem cells is their ability to be directed towards specific cell types of clinical interest, and can mature into functional cell types in vivo. While transplantations of fetal or ESC-derived tissues are known to illicit a host immunogenic response, autologous transplantations using cell types derived from one’s own iPSCs eliminate risks of tissue rejection and reduce the need for immunosuppressants. However, even with these benefits, cell therapy comes with significant hurdles that researchers are starting to overcome. In this review, we will discuss the various steps to ensure safety, efficacy and clinical practicality of cell replacement therapy in neurodegenerative diseases, in particular, Parkinson’s disease. Main body Parkinson’s disease (PD) results from a loss of dopaminergic neurons from the substantia nigra and is an ideal target for cell replacement therapy. Early trials using fetal midbrain material in the late 1980s have resulted in long term benefit for some patients, but there were multiple shortcomings including the non-standardization and quality control of the transplanted fetal material, and graft-induced dyskinesia that some patients experience as a result. On the other hand, pluripotent stem cells such as ESCs and iPSCs serve as an attractive source of cells because they can be indefinitely cultured and is an unlimited source of cells. Stem cell technologies and our understanding of the developmental potential of ESCs and iPSCs have deepened in recent years and a clinical trial for iPSC-derived dopaminergic cells is currently undergoing for PD patients in Japan. In this focused review, we will first provide a historical aspect of cell therapies in PD, and then discuss the various challenges pertaining to the safety and efficacy of stem cell-based cell transplantations, and how these hurdles were eventually overcome. Conclusion With the maturity of the iPSC technology, cell transplantation appears to be a safe and effective therapy. Grafts in non-human primates survive and remain functional for more than 2 years after transplantation, with no signs of tumorigenesis, indicating safety and efficacy of the treatment. However, immunosuppressants are still required because of the lack of “universal stem cells” that would not evoke an immune response. The results of ongoing and upcoming trials by a global consortium known as GForce-PD would be highly anticipated because the success of these trials would open up possibilities for using cell therapy for the treatment of PD and other degenerative diseases.

Possible roles of epigenetics in stem cell therapy for Parkinson’s disease

Epigenomics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 647-656
Author(s):  
Cassandra Thompson ◽  
Paulina Otero ◽  
Bhairavi Srinageshwar ◽  
Robert B Petersen ◽  
Gary L Dunbar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Therapeutic Potential ◽  
Epigenetic Changes ◽  
Epigenetic Alterations ◽  
Differential Gene ◽  
The Brain

Parkinson’s disease (PD) is a neurodegenerative disease with loss of dopaminergic neurons. PD has genetic and epigenetic influences that determine specific changes in the brain. Epigenetic changes result in defective methylation of genes leading to differential gene-expression causing PD. This review provides an overview of stem cell transplantations as potential therapies for PD, with a focus on the epigenetic changes, prior or following transplantation. To date, no reports have addressed epigenetic alterations following stem cell transplantation into the PD brain. Given the potential for affecting the efficacy of stem cell therapy, increased attention needs to be given to the epigenetic processes that occur during stem cell culture and transplantation to maximize the therapeutic potential of stem cells to PD.

scholarly journals A new area of stem cell therapy for Parkinson disease

2020 ◽  
Vol 7 (11) ◽  
pp. 4615
Author(s):  
Khaled M. Hassan ◽  
Zahra H. Alqarni ◽  
Ali A. Almontashri ◽  
Ahmed M. Allubly ◽  
Khalid A. Alalmaee ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Stem Cell ◽  
Animal Models ◽  
Pluripotent Stem Cells ◽  
Motor Complications ◽  
Disease Symptoms ◽  
Cell Sources ◽  
Induced Pluripotent

No treatment currently can be used in order to slow or even stop the progression of Parkinson's disease. Nowadays, researchers are already using stem cells to grow dopamine-producing nerve cells in the lab so that they can study the disease, especially in those cases where there is a known genetic cause for the condition. The development of the advanced cellular therapies and using induced pluripotent stem cells is making it possible to combat the progression of the disease without the resulting motor complications. It has been shown that the transplantation of many cell sources leads to reduce Parkinson’s disease symptoms in animal models.

Stem cell deficiency in Parkinson's disease

2005 ◽  
Vol 32 (06) ◽  
Author(s):  
GU Höglinger ◽  
P Rizk ◽  
WH Oertel ◽  
EC Hisch
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Stem Cell
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