Resolving Ethical Issues in Stem Cell Clinical Trials: The Example of Parkinson Disease

2010 ◽  
Vol 38 (2) ◽  
pp. 257-266 ◽  
Author(s):  
Bernard Lo ◽  
Lindsay Parham
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Parkinson Disease ◽  
Cell Transplantation ◽  
Ethical Issues ◽  
Current Therapy ◽  
Pluripotent Cells ◽  
Cord Injury

Stem cells derived from pluripotent cells offer the hope of new treatments for diseases for which current therapy is inadequate. Clinical trials are essential in developing effective and safe stem cell therapies and fulfilling this promise. However, such clinical trials raise ethical issues that are more complex than those raised in clinical trials using drugs, cord blood stem cells, or adult stem cells. Several clinical trials are now being carried out with stem cells derived from pluripotent cells, and many more can be expected in light of the rapid scientific progress in the field.Degenerative neurological diseases are desirable targets for stem cell clinical trials. The FDA has approved Phase 1 clinical trials of neural stem cell transplantation for Batten Disease, Pelizaeus-Merzbacher Disease, and spinal cord injury. In Parkinson Disease (PD), stem cell transplantation could correct the primary pathophysiological defect — inadequate levels of the neurotransmitter dopamine. Current treatment is unsatisfactory in late-stage PD.

Stem Cell Transplantation: A Promising Therapy for Spinal Cord Injury

2020 ◽  
Vol 15 (4) ◽  
pp. 321-331 ◽  
Author(s):  
Zhe Gong ◽  
Kaishun Xia ◽  
Ankai Xu ◽  
Chao Yu ◽  
Chenggui Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Therapeutic Potential ◽  
Embryonic Stem ◽  
Current Status ◽  
Cord Injury

Spinal Cord Injury (SCI) causes irreversible functional loss of the affected population. The incidence of SCI keeps increasing, resulting in huge burden on the society. The pathogenesis of SCI involves neuron death and exotic reaction, which could impede neuron regeneration. In clinic, the limited regenerative capacity of endogenous cells after SCI is a major problem. Recent studies have demonstrated that a variety of stem cells such as induced Pluripotent Stem Cells (iPSCs), Embryonic Stem Cells (ESCs), Mesenchymal Stem Cells (MSCs) and Neural Progenitor Cells (NPCs) /Neural Stem Cells (NSCs) have therapeutic potential for SCI. However, the efficacy and safety of these stem cellbased therapy for SCI remain controversial. In this review, we introduce the pathogenesis of SCI, summarize the current status of the application of these stem cells in SCI repair, and discuss possible mechanisms responsible for functional recovery of SCI after stem cell transplantation. Finally, we highlight several areas for further exploitation of stem cells as a promising regenerative therapy of SCI.

scholarly journals Human-Induced Neural and Mesenchymal Stem Cell Therapy Combined with a Curcumin Nanoconjugate as a Spinal Cord Injury Treatment

2021 ◽  
Vol 22 (11) ◽  
pp. 5966
Author(s):  
Pablo Bonilla ◽  
Joaquim Hernandez ◽  
Esther Giraldo ◽  
Miguel A. González-Pérez ◽  
Ana Alastrue-Agudo ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Neural Function ◽  
Neuroprotective Effects ◽  
Cord Injury

We currently lack effective treatments for the devastating loss of neural function associated with spinal cord injury (SCI). In this study, we evaluated a combination therapy comprising human neural stem cells derived from induced pluripotent stem cells (iPSC-NSC), human mesenchymal stem cells (MSC), and a pH-responsive polyacetal–curcumin nanoconjugate (PA-C) that allows the sustained release of curcumin. In vitro analysis demonstrated that PA-C treatment protected iPSC-NSC from oxidative damage in vitro, while MSC co-culture prevented lipopolysaccharide-induced activation of nuclear factor-κB (NF-κB) in iPSC-NSC. Then, we evaluated the combination of PA-C delivery into the intrathecal space in a rat model of contusive SCI with stem cell transplantation. While we failed to observe significant improvements in locomotor function (BBB scale) in treated animals, histological analysis revealed that PA-C-treated or PA-C and iPSC-NSC + MSC-treated animals displayed significantly smaller scars, while PA-C and iPSC-NSC + MSC treatment induced the preservation of β-III Tubulin-positive axons. iPSC-NSC + MSC transplantation fostered the preservation of motoneurons and myelinated tracts, while PA-C treatment polarized microglia into an anti-inflammatory phenotype. Overall, the combination of stem cell transplantation and PA-C treatment confers higher neuroprotective effects compared to individual treatments.

scholarly journals Clinical Trials of Stem Cell Treatment for Spinal Cord Injury

2020 ◽  
Vol 21 (11) ◽  
pp. 3994
Author(s):  
Kazuyoshi Yamazaki ◽  
Masahito Kawabori ◽  
Toshitaka Seki ◽  
Kiyohiro Houkin
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Clinical Trials ◽  
Stem Cell ◽  
Cell Transplantation ◽  
Current Knowledge ◽  
Special Focus ◽  
Cord Injury ◽  
Clinical Experiments

There are more than one million patients worldwide suffering paralysis caused by spinal cord injury (SCI). SCI causes severe socioeconomic problems not only to the patients and their caregivers but also to society; therefore, the development of innovative treatments is crucial. Many pharmacological therapies have been attempted in an effort to reduce SCI-related damage; however, no single therapy that could dramatically improve the serious long-term sequelae of SCI has emerged. Stem cell transplantation therapy, which can ameliorate damage or regenerate neurological networks, has been proposed as a promising candidate for SCI treatment, and many basic and clinical experiments using stem cells for SCI treatment have been launched, with promising results. However, the cell transplantation methods, including cell type, dose, transplantation route, and transplantation timing, vary widely between trials, and there is no consensus regarding the most effective treatment strategy. This study reviews the current knowledge on this issue, with a special focus on the clinical trials that have used stem cells for treating SCI, and highlights the problems that remain to be solved before the widespread clinical use of stem cells can be adopted.

scholarly journals Advances in the understanding of poor graft function following allogeneic hematopoietic stem-cell transplantation

2020 ◽  
Vol 11 ◽  
pp. 204062072094874
Author(s):  
Juan Chen ◽  
Hongtao Wang ◽  
Jiaxi Zhou ◽  
Sizhou Feng
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Function ◽  
Hematopoietic Stem ◽  
Poor Graft Function

Poor graft function (PGF) following allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is a life-threatening complication and is characterized by bilineage or trilineage blood cell deficiency and hypoplastic marrow with full chimerism. With the rapid development of allo-HSCT, especially haploidentical-HSCT, PGF has become a growing concern. The most common risk factors illustrated by recent studies include low dose of infused CD34+ cells, donor-specific antibody, cytomegalovirus infection, graft versus host disease (GVHD), iron overload and splenomegaly, among others. Because of the poor prognosis of PGF, it is crucial to uncover the underlying mechanism, which remains elusive. Recent studies have suggested that the bone marrow microenvironment may play an important role in the pathogenesis of PGF. Deficiency and dysfunction of endothelial cells and mesenchymal stem cells, elevated reactive oxygen species (ROS) levels, and immune abnormalities are believed to contribute to PGF. In this review, we also discuss recent clinical trials that evaluate the safety and efficacy of new strategies in patients with PGF. CD34+-selected stem-cell boost (SCB) is effective with an acceptable incidence of GVHD, despite the need for a second donation. Alternative strategies including the applications of mesenchymal stem cells, N-acetyl-l-cysteine (NAC), and eltrombopag have shown favorable outcomes, but further large-scale studies are needed due to the small sample sizes of the recent clinical trials.

Transplantation of Stem Cells as a Potential Therapeutic Strategy in Neurodegenerative Disorders

2020 ◽  
Vol 15 ◽  
Author(s):  
Tahereh Ebrahimi ◽  
Mozhgan Abasi ◽  
Fatemeh Seifar ◽  
Shirin Eyvazi ◽  
Mohammas Saeid Hejazi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Neurological Diseases ◽  
Experimental Studies ◽  
Embryonic Stem ◽  
Lysosomal Storage ◽  
Cord Injury

: Stem cells are considered to have significant capacity to differentiate into various cell types in humans or animals. Unlike specialized cells, these cells can proliferate several times to produce millions of cells. Nowadays, pluripotent stem cells are important candidates to provide a renewable source for replacement of cells in tissues of interest. The damage to neurons and glial cells in the brain or spinal cord is present in neurological disorders such as Amyotrophic lateral sclerosis, stroke, Parkinson’s disease, multiple sclerosis, Alzheimer’s disease, Huntington’s disease, spinal cord injury, lysosomal storage disorder, epilepsy, and glioblastoma. Therefore, stem cell transplantation can be used as novel therapeutic approach in cases of brain and spinal cord damage. Recently, researchers have generated neuron-like cells and glial-like cells from embryonic stem cells, mesenchymal stem cells, and neural stem cells. In addition, several experimental studies have been performed for developing stem cell transplantation in brain tissue. Herein, we focus on stem cell therapy to regenerate injured tissue resulting from neurological diseases and then discuss possible differentiation pathways of stem cells to the renewal of neurons.

scholarly journals Human Stem Cell Transplantation for Retinal Degenerative Diseases. Where Are We Now?

Medicina ◽  
2022 ◽  
Vol 58 (1) ◽  
pp. 102
Author(s):  
Ignacio Alcalde ◽  
Cristina Sánchez-Fernández ◽  
Carla Martín ◽  
Nagore De Pablo ◽  
Nahla Jemni-Damer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Degenerative Diseases ◽  
Age Related ◽  
Retinal Degenerative Diseases

Background and Objectives: Irreversible visual impairment is mainly caused by retinal degenerative diseases such as age-related macular degeneration and retinitis pigmentosa. Stem cell research has experienced rapid progress in recent years, and researchers and clinical ophthalmologists are trying to implement this promising technology to treat retinal degeneration. The objective of this systematic review is to analyze currently available data from clinical trials applying stem cells to treat human retinal diseases. Materials and Methods: We performed a systematic literature search in PubMed to identify articles related with stem cell therapies to retinal diseases published prior to September 2021. Furthermore, a systematic search in ClinicalTrials (NIH U.S. National Library of Medicine) was performed to identify clinical trials using stem cells to treat retinal diseases. A descriptive analysis of status, conditions, phases, interventions, and outcomes is presented here. Conclusions: To date, no available therapy based on stem cell transplantation is approved for use with patients. However, numerous clinical trials are currently finishing their initial phases and, in general, the outcomes related to implantation techniques and their long-term safety seem promising. In the next few years, we expect to see quantifiable results pertaining to visual function improvement.

scholarly journals Evaluation of the Clinical Efficacy of Stem Cell Transplantation in the Treatment of Spinal Cord Injury: A Systematic Review and Meta-analysis

2021 ◽  
Vol 30 ◽  
pp. 096368972110678
Author(s):  
Qiao-Rui Tang ◽  
Hui Xue ◽  
Qiao Zhang ◽  
Ying Guo ◽  
Hao Xu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Treatment Time ◽  
Cell Numbers ◽  
Cord Injury

Stem cell transplantation has been applied to treat spinal cord injury (SCI) in clinical trials for many years. However, the clinical efficacies of stem cell transplantation in SCI have been quite diverse. The purpose of our study was to systematically investigate the efficacy of stem cell transplantation in patients with SCI. The PubMed, Web of Science, Ovid-Medline, Cochrane Library, China National Knowledge Infrastructure, VIP, Wanfang, and SinoMed databases were searched until October 27, 2020. Quantitative and qualitative data were analyzed by Review Manager 5.3 and R. Nine studies ( n = 328) were included, and the overall risk of bias was moderate. The ASIA Impairment Scale (AIS) grading improvement rate was analyzed in favor of stem cell transplantation group [odds ratio (OR) = 6.06, 95% confidence interval (CI): 3.16–11.62, P < 0.00001]. Urodynamic indices also showed improvement in bladder function. In subgroup analyses, the results indicated that in patients with complete (AIS A) SCI, with the application of cell numbers between n*(107–108), two cell types (i.e., bone marrow–derived mesenchymal stem cells and bone marrow mononuclears), and treatment time of more than 6 months, stem cell transplantation was more beneficial for sensorimotor function ( P < 0.05 for all groups). The risk of fever incidence in the stem cell transplantation group was 4.22 (95% CI: 1.7–10.22, P = 0.001), and principal component analysis (PCA) suggested it was more related to transplanted cell numbers. Thus, stem cell transplantation can promote functional recovery in SCI patients. Moreover, the type and quantity of transplanted stem cells and treatment time are important factors affecting the therapeutic effect of stem cell transplantation in SCI. Further studies are needed to evaluate the effects and elucidate the mechanisms of these factors on stem cell therapy in SCI.

A Randomized Trial of Two 2-Dose Influenza Vaccination Strategies for Patients Following Autologous Hematopoietic Stem Cell Transplantation

2020 ◽  
Author(s):  
Benjamin W Teh ◽  
Vivian K Y Leung ◽  
Francesca L Mordant ◽  
Sheena G Sullivan ◽  
Trish Joyce ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Influenza Vaccination ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Influenza B ◽  
High Dose ◽  
Hematopoietic Stem

Abstract Background Seroprotection and seroconversion rates are not well understood for 2-dose inactivated influenza vaccination (IIV) schedules in autologous hematopoietic stem cell transplantation (autoHCT) patients. Methods A randomized, single-blind, controlled trial of IIV in autoHCT patients in their first year post-transplant was conducted. Patients were randomized 1:1 to high-dose (HD) IIV followed by standard dose (SD) vaccine (HD-SD arm) or 2 SD vaccines (SD-SD arm) 4 weeks apart. Hemagglutination inhibition (HI) assay for IIV strains was performed at baseline, 1, 2, and 6 months post–first dose. Evaluable primary outcomes were seroprotection (HI titer ≥40) and seroconversion (4-fold titer increase) rates and secondary outcomes were geometric mean titers (GMTs), GMT ratios (GMRs), adverse events, influenza-like illness (ILI), and laboratory-confirmed influenza (LCI) rates and factors associated with seroconversion. Results Sixty-eight patients were enrolled (34/arm) with median age of 61.5 years, majority male (68%) with myeloma (68%). Median time from autoHCT to vaccination was 2.3 months. For HD-SD and SD-SD arms, percentages of patients achieving seroprotection were 75.8% and 79.4% for H1N1, 84.9% and 88.2% for H3N2 (all P &gt; .05), and 78.8% and 97.1% for influenza-B/Yamagata (P = .03), respectively. Seroconversion rates, GMTs and GMRs, and number of ILI or LCIs were not significantly different between arms. Adverse event rates were similar. Receipt of concurrent cancer therapy was independently associated with higher odds of seroconversion (OR, 4.3; 95% CI, 1.2–14.9; P = .02). Conclusions High seroprotection and seroconversion rates against all influenza strains can be achieved with vaccination as early as 2 months post-autoHCT with either 2-dose vaccine schedules. Clinical Trials Registration Australian New Zealand Clinical Trials Registry: ACTRN12619000617167.

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