Next-generation stem cells — ushering in a new era of cell-based therapies

Kimbrel, Erin A.; Lanza, Robert

doi:10.1038/s41573-020-0064-x

Cited by 216 publications

(159 citation statements)

References 175 publications

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“…Derivation of large quantities of hiPSC-derived cardiomyocytes and hepatocytes is of particular interest for drug development, toxicology studies, and regenerative medicine (Kimbrel and Lanza, 2020;Sharma et al, 2020). To generate cardiomyocytes, we adopted a kit-based protocol for automated differentiation of hPSCs ( Figure 7A).…”

Section: Standardized Production Of Functional Cardiomyocytes and Hepmentioning

confidence: 99%

“…Human pluripotent stem cells (hPSCs) such as hiPSCs are characterized by extensive self-renewal capacity and differentiation into all somatic cell types, thereby enabling novel approaches to model, diagnose, and treat human diseases ( Kimbrel and Lanza, 2020 ; Sato et al, 2019 ; Sharma et al, 2020 ). Considering the tremendous potential of hiPSCs, several challenges still remain to be addressed for their efficient and safe utilization.…”

Section: Introductionmentioning

confidence: 99%

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Robotic High-Throughput Biomanufacturing and Functional Differentiation of Human Pluripotent Stem Cells

Tristan

Ormanoglu

Slamecka

et al. 2020

Preprint

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Efficient translation of human induced pluripotent stem cells (hiPSCs) depends on implementing scalable cell manufacturing strategies that ensure optimal self-renewal and functional differentiation. Currently, manual culture of hiPSCs is highly variable and labor-intensive posing significant challenges for high-throughput applications. Here, we established a robotic platform and automated all essential steps of hiPSC culture and differentiation under chemically defined conditions. This streamlined approach allowed rapid and standardized manufacturing of billions of hiPSCs that can be produced in parallel from up to 90 different patient-and disease-specific cell lines. Moreover, we established automated multi-lineage differentiation to generate primary embryonic germ layers and more mature phenotypes such as neurons, cardiomyocytes, and hepatocytes. To validate our approach, we carefully compared robotic and manual cell culture and performed molecular and functional cell characterizations (e.g. bulk culture and single-cell transcriptomics, mass cytometry, metabolism, electrophysiology, Zika virus experiments) in order to benchmark industrial-scale cell culture operations towards building an integrated platform for efficient cell manufacturing for disease modeling, drug screening, and cell therapy. Combining stem cell-based models and non-stop robotic cell culture may become a powerful strategy to increase scientific rigor and productivity, which are particularly important during public health emergencies (e.g. opioid crisis, COVID-19 pandemic).

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Section: Standardized Production Of Functional Cardiomyocytes and Hepmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Robotic High-Throughput Biomanufacturing and Functional Differentiation of Human Pluripotent Stem Cells

Tristan

Ormanoglu

Slamecka

et al. 2020

Preprint

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“…Despite the lack of FDA approval, the allure of profits from stem cell therapies have sparked a growing industry of DTC clinics that advertise and provide non-FDA approved therapies. These clinics often employ predatory practices by targeting patients with chronic or severe conditions that have complex or multifactorial etiologies for which conventional, evidence-based therapy options may have run out (Frow et al 2019) such as cancer, hepatitis, neurodegeneration and vision loss (Kimbrel and Lanza 2020). Insurance companies typically will not cover non-FDA approved treatments, leading to crowdfunding campaigns by desperate patients (Snyder, Turner, and Crooks 2018), which result in individuals paying anywhere from $2,500 to over $50,000 per non-regulated stem cell injection (P. Knoepfler 2019).…”

Section: The Rise and Risks Of Unregulated Stem Cell Clinicsmentioning

confidence: 99%

Stem the Tide of Predatory Stem Cell Clinics: State and FDA Coordination to Protect Patients

McCutcheon

Malloy

Hall

et al. 2020

JSPG

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While stem cell therapies hold promise as regenerative treatments for combating a variety of conditions, the majority of these therapies remain in clinical trials without sufficient evidence for current clinical use. Predatory direct-to-consumer stem cell clinics (hereafter, DTC clinics), undeterred by a lack of clinical evidence, continue to offer unapproved stem cell injections to patients desperate to treat chronic conditions. These clinics can pose significant physical and financial harm to patients as their therapies are not without risks. Clinics rarely practice the requisite level of follow-up care required by clinical trials. To promote the safety and well-being of patients treated in stem cell clinics, we propose additional funding to support the Federal Food and Drug Administration (FDA) and state-level health departments’ oversight of DTC clinics. The FDA will likely experience a substantial financial burden from enforcing regulations, given that there are hundreds of DTC clinics in the U.S. This number is expected to continue rising, as evidenced by a 114% increase in DTC clinics between 2015 and 2017 (P. S. Knoepfler 2019). We propose that the FDA appropriate additional funding to support state level government enforcement and address this impending shortcoming. Additionally, we suggest state legislatures enact registry laws to prevent DTC clinics from avoiding federal regulations and enable local governments to address low-risk offenders as needed. These laws would enable states to take a more proactive role in patient protections, while also allowing the FDA to more effectively target its resources towards high-risk DTC business.

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“…Other major breakthroughs have been made in the field of stem cell therapies. In addition to traditional hematopoietic stem cell transplants, mesenchymal stem cells or cells differentiated from induced pluripotent stem cell (iPSC) developed from the patient's own cells or embryonic stem cells have been actively investigated for the therapy or regeneration of damaged tissue [14,15].…”

Section: Introductionmentioning

confidence: 99%

Imaging of cell-based therapy using ⁸⁹Zr-oxine ex vivo cell labeling for positron emission tomography

Kurebayashi¹,

Choyke²,

Sato³

2021

Nanotheranostics

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With the rapid development of anti-cancer cell-based therapies, such as adoptive T cell therapies using tumor-infiltrating T cells, T cell receptor transduced T cells, and chimeric antigen receptor T cells, there has been a growing interest in imaging technologies to non-invasively track transferred cells in vivo. Cell tracking using ex vivo cell labeling with positron emitting radioisotopes for positron emission tomography (PET) imaging has potential advantages over single-photon emitting radioisotopes. These advantages include intrinsically higher resolution, higher sensitivity, and higher signal-to-background ratios. Here, we review the current status of recently developed Zirconium-89 (89 Zr)-oxine ex vivo cell labeling with PET imaging focusing on its applications and future perspectives. Labeling of cells with 89 Zr-oxine is completed in a series of relatively simple steps, and its low radioactivity doses required for imaging does not interfere with the proliferation or function of the labeled immune cells. Preclinical studies have revealed that 89 Zr-oxine PET allows high-resolution in vivo tracking of labeled cells for 1-2 weeks after cell transfer both in mice and non-human primates. These results provide a strong rationale for the clinical translation of 89 Zr-oxine PET-based imaging of cell-based therapy.

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Next-generation stem cells — ushering in a new era of cell-based therapies

Cited by 216 publications

References 175 publications

Robotic High-Throughput Biomanufacturing and Functional Differentiation of Human Pluripotent Stem Cells

Robotic High-Throughput Biomanufacturing and Functional Differentiation of Human Pluripotent Stem Cells

Stem the Tide of Predatory Stem Cell Clinics: State and FDA Coordination to Protect Patients

Imaging of cell-based therapy using ⁸⁹Zr-oxine ex vivo cell labeling for positron emission tomography

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Next-generation stem cells — ushering in a new era of cell-based therapies

Cited by 216 publications

References 175 publications

Robotic High-Throughput Biomanufacturing and Functional Differentiation of Human Pluripotent Stem Cells

Robotic High-Throughput Biomanufacturing and Functional Differentiation of Human Pluripotent Stem Cells

Stem the Tide of Predatory Stem Cell Clinics: State and FDA Coordination to Protect Patients

Imaging of cell-based therapy using 89Zr-oxine ex vivo cell labeling for positron emission tomography

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Product

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Imaging of cell-based therapy using ⁸⁹Zr-oxine ex vivo cell labeling for positron emission tomography