FDA regulation of adipose cell use in clinical trials and clinical translation

2022 ◽  
pp. 265-310
Author(s):  
Mary Ann Chirba ◽  
Veronica Morgan Jones ◽  
Patsy Simon ◽  
Adam J. Katz
Keyword(s):  
Clinical Trials ◽  
Clinical Translation ◽  
Adipose Cell

scholarly journals Cell Therapy for Stroke: A Mechanistic Analysis

Neurosurgery ◽  
2020 ◽  
Author(s):  
Ben Jiahe Gu ◽  
David K Kung ◽  
Han-Chiao Isaac Chen
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Cell Therapy ◽  
Clinical Translation ◽  
Stroke Survivors ◽  
Cell Replacement ◽  
Preclinical Data ◽  
Promising Strategy ◽  
Mechanistic Analysis

Abstract Cell therapy has been widely recognized as a promising strategy to enhance recovery in stroke survivors. However, despite an abundance of encouraging preclinical data, successful clinical translation remains elusive. As the field continues to advance, it is important to reexamine prior clinical trials in the context of their intended mechanisms, as this can inform future preclinical and translational efforts. In the present work, we review the major clinical trials of cell therapy for stroke and highlight a mechanistic shift between the earliest studies, which aimed to replace dead and damaged neurons, and later ones that focused on exploiting the various neuromodulatory effects afforded by stem cells. We discuss why both mechanisms are worth pursuing and emphasize the means through which cell replacement can still be achieved.

Clinical Translation of Recommendations from Randomized Clinical Trials on Patching Regimen for Amblyopia

Ophthalmology ◽  
2013 ◽  
Vol 120 (4) ◽  
pp. 657-662 ◽  
Author(s):  
Ya-Ping Jin ◽  
Amy H.Y. Chow ◽  
Linda Colpa ◽  
Agnes M.F. Wong
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Clinical Translation

scholarly journals Selective inhibition of the p38α MAPK–MK2 axis inhibits inflammatory cues including inflammasome priming signals

2018 ◽  
Vol 215 (5) ◽  
pp. 1315-1325 ◽  
Author(s):  
Chun Wang ◽  
Susan Hockerman ◽  
E. Jon Jacobsen ◽  
Yael Alippe ◽  
Shaun R. Selness ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Mrna Decay ◽  
Selective Inhibition ◽  
Mrna Degradation ◽  
Cytokine Expression ◽  
Clinical Translation ◽  
Tnf Α ◽  
P38α Mapk ◽  
Nlrp3 Expression

p38α activation of multiple effectors may underlie the failure of global p38α inhibitors in clinical trials. A unique inhibitor (CDD-450) was developed that selectively blocked p38α activation of the proinflammatory kinase MK2 while sparing p38α activation of PRAK and ATF2. Next, the hypothesis that the p38α–MK2 complex mediates inflammasome priming cues was tested. CDD-450 had no effect on NLRP3 expression, but it decreased IL-1β expression by promoting IL-1β mRNA degradation. Thus, IL-1β is regulated not only transcriptionally by NF-κB and posttranslationally by the inflammasomes but also posttranscriptionally by p38α–MK2. CDD-450 also accelerated TNF-α and IL-6 mRNA decay, inhibited inflammation in mice with cryopyrinopathy, and was as efficacious as global p38α inhibitors in attenuating arthritis in rats and cytokine expression by cells from patients with cryopyrinopathy and rheumatoid arthritis. These findings have clinical translation implications as CDD-450 offers the potential to avoid tachyphylaxis associated with global p38α inhibitors that may result from their inhibition of non-MK2 substrates involved in antiinflammatory and housekeeping responses.

scholarly journals When Origin Matters: Properties of Mesenchymal Stromal Cells From Different Sources for Clinical Translation in Kidney Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Sandra Calcat-i-Cervera ◽  
Clara Sanz-Nogués ◽  
Timothy O'Brien
Keyword(s):  
Cell Culture ◽  
Clinical Trials ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Scale Up ◽  
Clinical Translation ◽  
Health Concern ◽  
Optimal Scale ◽  
Wide Range ◽  
Processing Variables

Advanced therapy medicinal products (ATMPs) offer new prospects to improve the treatment of conditions with unmet medical needs. Kidney diseases are a current major health concern with an increasing global prevalence. Chronic renal failure appears after many years of impairment, which opens a temporary window to apply novel therapeutic approaches to delay or halt disease progression. The immunomodulatory, anti-inflammatory, and pro-regenerative properties of mesenchymal stromal cells (MSCs) have sparked interest for their use in cell-based regenerative therapies. Currently, several early-phase clinical trials have been completed and many are ongoing to explore MSC safety and efficacy in a wide range of nephropathies. However, one of the current roadblocks to the clinical translation of MSC therapies relates to the lack of standardization and harmonization of MSC manufacturing protocols, which currently hinders inter-study comparability. Studies have shown that cell culture processing variables can have significant effects on MSC phenotype and functionality, and these are highly variable across laboratories. In addition, heterogeneity within MSC populations is another obstacle. Furthermore, MSCs may be isolated from several sources which adds another variable to the comparative assessment of outcomes. There is now a growing body of literature highlighting unique and distinctive properties of MSCs according to the tissue origin, and that characteristics such as donor, age, sex and underlying medical conditions may alter the therapeutic effect of MSCs. These variables must be taken into consideration when developing a cell therapy product. Having an optimal scale-up strategy for MSC manufacturing is critical for ensuring product quality while minimizing costs and time of production, as well as avoiding potential risks. Ideally, optimal scale-up strategies must be carefully considered and identified during the early stages of development, as making changes later in the bioprocess workflow will require re-optimization and validation, which may have a significant long-term impact on the cost of the therapy. This article provides a summary of important cell culture processing variables to consider in the scale-up of MSC manufacturing as well as giving a comprehensive review of tissue of origin-specific biological characteristics of MSCs and their use in current clinical trials in a range of renal pathologies.

scholarly journals Blowing up Neural Repair for Stroke Recovery

Stroke ◽  
2020 ◽  
Vol 51 (10) ◽  
pp. 3169-3173
Author(s):  
Nick S. Ward ◽  
S. Thomas Carmichael
Keyword(s):  
Clinical Trials ◽  
Clinical Translation ◽  
Stroke Recovery ◽  
Preclinical Studies ◽  
Neural Repair ◽  
Biological Targets ◽  
Blowing Up ◽  
Biological Target ◽  
Multicenter Clinical Trials ◽  
The Brain

The repair and recovery of the brain after stroke is a field that is emerging in its preclinical science and clinical trials. However, recent large, multicenter clinical trials have been negative, and conflicting results emerge on biological targets in preclinical studies. The coalescence of negative clinical translation and confusion in preclinical studies raises the suggestion that perhaps the field of stroke recovery faces a fate similar to stroke neuroprotection, with interesting science ultimately proving difficult to translate to the clinic. This review highlights improvements in 4 areas of the stroke neural repair field that should reorient the field toward successful clinical translation: improvements in rodent genetic models of stroke recovery, consideration of the biological target in stroke recovery, stratification in clinical trials, and the use of appropriate clinical trial end points.

scholarly journals Advances in Lipid-Based Nanoparticles for Cancer Chemoimmunotherapy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 520
Author(s):  
Tianqi Wang ◽  
Yusuke Suita ◽  
Saradha Miriyala ◽  
Jordan Dean ◽  
Nikos Tapinos ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cancer Therapy ◽  
Cancer Treatment ◽  
Clinical Translation ◽  
Hybrid Nanoparticles ◽  
Future Perspectives ◽  
Preclinical Research ◽  
Delivery Platform

Nanomedicines have shown great potential in cancer therapy; in particular, the combination of chemotherapy and immunotherapy (namely chemoimmunotherapy) that is revolutionizing cancer treatment. Currently, most nanomedicines for chemoimmunotherapy are still in preclinical and clinical trials. Lipid-based nanoparticles, the most widely used nanomedicine platform in cancer therapy, is a promising delivery platform for chemoimmunotherapy. In this review, we introduce the commonly used immunotherapy agents and discuss the opportunities for chemoimmunotherapy mediated by lipid-based nanoparticles. We summarize the clinical trials involving lipid-based nanoparticles for chemoimmunotherapy. We also highlight different chemoimmunotherapy strategies based on lipid-based nanoparticles such as liposomes, nanodiscs, and lipid-based hybrid nanoparticles in preclinical research. Finally, we discuss the challenges that have hindered the clinical translation of lipid-based nanoparticles for chemoimmunotherapy, and their future perspectives.

scholarly journals The Use of Platelet-Rich Plasma (PRP) for the Management of Non-union Fractures

2021 ◽  
Author(s):  
Christian Andersen ◽  
Nicholas M. Wragg ◽  
Maryam Shariatzadeh ◽  
Samantha Louise Wilson
Keyword(s):  
Clinical Trials ◽  
Bone Healing ◽  
Platelet Rich Plasma ◽  
Clinical Effectiveness ◽  
Biologic Agents ◽  
Clinical Translation ◽  
Randomised Clinical Trials ◽  
Non Union ◽  
Significant Challenge ◽  
Level I

Abstract Purpose of Review The treatment of non-union fractures represents a significant challenge for orthopaedic surgeons. In recent years, biologic agents have been investigated and utilised to support and improve bone healing. Among these agents, platelet-rich plasma (PRP) is an emerging strategy that is gaining popularity. The aim of this review is to evaluate the current literature regarding the application and clinical effectiveness of PRP injections, specifically for the treatment of non-union fractures. Recent Findings The majority of published studies reported that PRP accelerated fracture healing; however, this evidence was predominantly level IV. The lack of randomised, clinical trials (level I–II evidence) is currently hampering the successful clinical translation of PRP as a therapy for non-union fractures. This is despite the positive reports regarding its potential to heal non-union fractures, when used in isolation or in combination with other forms of treatment. Summary Future recommendations to facilitate clinical translation and acceptance of PRP as a therapy include the need to investigate the effects of administering higher volumes of PRP (i.e. 5–20 mL) along with the requirement for more prolonged (> 11 months) randomised clinical trials.

Localization of Gallium-67 in Peritoneal Cells by Electron Microscopic Autoradiography

1973 ◽  
Vol 31 ◽  
pp. 404-405
Author(s):  
D. C. Swartzendruber ◽  
Norma L. Idoyaga-Vargas
Keyword(s):  
Clinical Trials ◽  
Soft Tissue ◽  
Tumor Tissue ◽  
Soft Tissue Tumors ◽  
Clinical Usefulness ◽  
Electron Microscopic ◽  
Normal Cells ◽  
Electron Microscopic Autoradiography ◽  
Peritoneal Cells ◽  
Gallium 67

The radionuclide gallium-67 (67Ga) localizes preferentially but not specifically in many human and experimental soft-tissue tumors. Because of this localization, 67Ga is used in clinical trials to detect humar. cancers by external scintiscanning methods. However, the fact that 67Ga does not localize specifically in tumors requires for its eventual clinical usefulness a fuller understanding of the mechanisms that control its deposition in both malignant and normal cells. We have previously reported that 67Ga localizes in lysosomal-like bodies, notably, although not exclusively, in macrophages of the spocytaneous AKR thymoma. Further studies on the uptake of 67Ga by macrophages are needed to determine whether there are factors related to malignancy that might alter the localization of 67Ga in these cells and thus provide clues to discovering the mechanism of 67Ga localization in tumor tissue.

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