By providing access to a diverse collection of high-quality patient-derived cell lines, NINDS facilitates breakthroughs in understanding diseases like Alzheimer’s and amyotrophic lateral sclerosis (ALS).

Partnering with SAMPLED for secure storage and efficient distribution, NINDS supports researchers worldwide in developing novel treatments and expanding knowledge in the field. This blog explores the impact of the NINDS Biorepository on cellular research and the crucial role of advanced biobanking practices, such as those implemented by SAMPLED, in preserving the integrity of these essential resources.

The National Institute of Neurological Disorders and Stroke

NINDS supports furthering our understanding of neurological disorders through education, funding, and its biorepository¹. The NINDS biorepository maintains a diverse set of patient-derived cell lines, including induced pluripotent stem cells (iPSCs) and fibroblasts for many neurological disorders such as Alzheimer’s disease. By providing high-quality cell lines for research and clinical trials, NINDS enables researchers to derive crucial information about neurological disorders and promotes the generation of novel therapies and management strategies. NINDS relies on SAMPLED as a trusted partner to securely store and distribute cells.

Sample Storage Challenges in Modern Research

Research institutions face several challenges when storing samples and reagents. Small institutions can struggle with capacity and having sufficiently skilled staff to manage storage infrastructure and data security, while large institutions can struggle with adapting their existing infrastructure to evolving research environments. For instance, personalized medicine and the discovery of biomarkers for neurological diseases from diverse tissue types mean that more samples may need to be stored for individual patients^2–4.

The high volume of samples necessitates more automated approaches to sample security. Manual monitoring becomes increasingly inefficient and unreliable as the volume of samples increases. Institutions like NINDS possess highly valuable cell lines sensitive to temperature fluctuations. Thus, they have an increased need for robust systems to ensure sample integrity. Beyond physical security, biorepositories require robust cybersecurity measures to safeguard patient data. In addition to protecting data, it is essential that samples and their related information are well-organized and readily accessible to authorized personnel.

Benefits of Advanced Biobanking

Advanced biobanking systems, such as those employed by SAMPLED in its partnership with NINDS, help to overcome many of these challenges, offering enhanced sample quality and security to bolster research efforts.

Scalability

Flexible storage capacity is essential for optimal biobanking and allows researchers to tackle more ambitious research projects incorporating more patient samples, treatments, and timepoints.

Security

Modern biobanks incorporate robust physical and data security systems to ensure patient data and samples are handled appropriately and are less vulnerable to theft or loss due to disasters. These systems include data encryption, dedicated alarm systems, real-time monitoring, and adherence to international regulatory standards such as the International Society for Biological and Environmental Repositories (ISBER)⁵ and the Health Insurance Portability and Accountability Act (HIPAA)⁶.

Automation

Modern biobanks use automation to streamline the retrieval and processing of different samples. This helps to eliminate the chances of human error, which can accelerate sample degradation and lead to sample misplacement.

The SAMPLED Framework

SAMPLED is the dedicated supplier for the NINDS Human Cell and Data Repository (NHCDR) and is trusted by other government institutions for sample storage and distribution. SAMPLED maintains a modern sample collection, storage and analysis infrastructure to help streamline the next generation of therapies for neurological disorders.

Automation

SAMPLED uses high-end automated instrumentation throughout its sample collection and storage pipeline. This helps ensure samples are stored at optimal temperatures, giving the best chances for high-quality data.

Security

SAMPLED uses dedicated alarm systems and real-time monitoring for each of its 600 mechanical -80°C freezers to ensure samples are always maintained appropriately. SampledSphere is our Title 21 CFR part 11⁷ and HIPAA-compliant cloud-based portal where clients can view their data and receive reporting tailored to their needs.

Ordering NINDS Cell Lines

SAMPLED facilitates efficient ordering of cell lines from NINDS to drive the next generation of treatments for neurological disorders.

Visit this page for a detailed guide.

Conclusion

The NINDS Biorepository, bolstered by its partnership with SAMPLED, is transforming cellular research by providing researchers with secure, high-quality, patient-derived cell lines. This resource accelerates breakthroughs in understanding neurological disorders and developing novel therapies.

With advanced biobanking practices, including automated storage, robust data security, and scalable infrastructure, NINDS ensures the preservation and accessibility of critical research materials. As a result, the biorepository plays a pivotal role in advancing scientific knowledge and treatment possibilities for neurological diseases.

Do you need high-quality cell lines for your neurology research?

Download our comprehensive whitepaper, which covers the importance of NINDS and advanced biobanking practice in more detail.

Download white paper

References

1. The NINDS Human Cell and Data Repository – Providing iPSCs and Fibroblasts for the Study of Neurological Disease. March 1, 2021. Accessed October 29, 2024. https://nindsgenetics.org/

2. Zeng X, Chen Y, Sehrawat A, et al. Alzheimer blood biomarkers: practical guidelines for study design, sample collection, processing, biobanking, measurement and result reporting. Mol Neurodegener. 2024;19(1):40. doi:10.1186/s13024-024-00711-1

3. Jiao LL, Dong HL, Liu MM, et al. The potential roles of salivary biomarkers in neurodegenerative diseases. Neurobiology of Disease. 2024;193:106442. doi:10.1016/j.nbd.2024.106442

4. Król-Grzymała A, Sienkiewicz-Szłapka E, Fiedorowicz E, Rozmus D, Cieślińska A, Grzybowski A. Tear Biomarkers in Alzheimer’s and Parkinson’s Diseases, and Multiple Sclerosis: Implications for Diagnosis (Systematic Review). Int J Mol Sci. 2022;23(17):10123. doi:10.3390/ijms231710123

5. ISBER. Accessed October 30, 2024. https://isber.org

6. CDC. Health Insurance Portability and Accountability Act of 1996 (HIPAA). Public Health Law. September 10, 2024. Accessed October 30, 2024. https://www.cdc.gov/phlp/php/resources/health-insurance-portability-and-accountability-act-of-1996-hipaa.html

7. CFR – Code of Federal Regulations Title 21. Accessed October 30, 2024. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=11

How the Sampled’s GIAB Meets the Challenges of PBMC Isolation

As living cells, PBMCs are vulnerable to many environmental variables. Temperature and time before processing can affect cell viability and impact immunological phenotypes such as cytokine production, which can hamper studies that require statistically reproducible results. Here, we break down the different stages of PBMC isolation and discuss how mismanagement of these processes can ruin studies and lead to long and costly delays in the drug development pipeline. For each challenge discussed, we provide a description of the robust solutions that Sampled’s GIAB offers.

Logistics and Processing

PBMCs are best isolated from whole blood within twenty-four hours of phlebotomy, and that has not been frozen. In multicentre trials, whole blood samples can be subjected to temperatures ranging from  -1 °C to 35 °C, affecting viability⁴, the effectiveness of cryopreservation⁵, and important immunological phenotypes⁴. Time prior to analysis is also an important factor⁶. Contamination with other cell types such as granulocytes can occur during PBMC isolation and affect T-cell activation⁷. Thus, robust and reproducible isolation protocols are essential.

How the Sampled’s GIAB enhances PBMC logistics and processing

Streamlined Logistics and Data Storage

We provide optimal transport materials through our custom kitting service and organize a trusted courier to ensure all samples arrive on time and are maintained in optimal conditions. We also ensure accurate and secure data collection and storage and allow clients to view and audit their data via our cloud platform, SampledSphere.

Automated and Manual Processing

At Sampled, we use the Hamilton EasyBlood, a high-capacity automated instrument for PBMC isolation. Automation minimizes human errors and allows samples to be processed simultaneously, preventing inter-run variation and ensuring the isolation of a pure pool of PBMCs. We also have on-site experts to perform manual isolation for challenging, low-volume, or low-cell number samples. This combination allows us to maximize study success.

Sample Handling and Storage

Handling and storage conditions can introduce variables that impact PBMC viability and function. In fact, temperature prior to cryopreservation of PBMCs can significantly impact immunological phenotypes after thawing, such as interferon-gamma production by T-cells⁵. Lack of suitable storage capacity can mean that precious samples are left to deteriorate and cannot be used for follow-up studies. Large longitudinal studies can require decades of secure dedicated storage space that many facilities cannot provide. Furthermore, having reliable backup plans for power outages and freezer breakdowns can make the difference between study success and needing to start from scratch.

Sampled’s GIAB Provides Handling and Storage Capacity to Meet the Requirements of any Study

Storage

The Sampled GIAB is home to 600 -80 °C freezers with a capacity for 1,000 freezers and adheres strictly to the International Society for Biological and Environmental Repositories standards⁸. This means no sample is left to deteriorate at suboptimal conditions and we can accommodate large-scale studies that require high-volume, secure storage.

Study Management

We work with clients to immortalize samples, ensuring, where possible, that there is enough left over for future studies. Our broad processing capabilities mean we can process and store multiple important biomolecules from PBMCs, such as DNA, protein, and serum.

Disaster Recovery

Sometimes disasters like freezer malfunctions are unavoidable, and having a detailed disaster recovery plan can help to mitigate risk. Sampled offers an on-call team of technical experts who can retrieve your samples and store them in our freezers with dedicated alarms and multiple backup generators, helping to secure your samples should the worst happen.

Analytical Considerations

Data analysis is where all of the variables introduced in PBMC processing appear, and it can be challenging to determine what results are genuine and which are artifacts. Quality control (QC) is important to determine cell viability and number and can help identify confounding variables that may have been introduced. As such, failure to perform QC can waste time and resources.

How Sampled’s GIAB Enhances Data Analysis

QC

For PBMC counting and viability tests, Sampled uses standardized pre-calibrated single-use cassettes and automated fluorescence microscopy (ChemoMetec Nucleocounter®). We perform plasma QC with the Lunatic spectrophotometer from Unchained Labs and cDrop analysis software. QC saves time and resources by ensuring only good-quality samples are brought forward for analysis.

Dedicated Bioinformatics Team

Sampled has a team of expert bioinformaticians who can use sophisticated analyses that take confounding factors into account. Even if damaging variables have been introduced, our team can salvage your data, allowing you to achieve study success even where best practices were not followed.

PBMCs are pivotal in immunological research and many drug discovery pipelines. However, PBMC processing is fraught with challenges, including variability in isolation and environmental sensitivity, which can compromise research integrity. Sampled’s GIAB addresses these obstacles through streamlined logistics, robust quality control, and advanced storage solutions, ensuring sample viability and purity. By mitigating variables at each processing stage, the Sampled GIAB enhances the reproducibility of immunological research, accelerating drug development and improving study outcomes.

If you want to learn more about how Sampled’s GIAB can help you succeed with PBMC studies, you can check out our latest white paper[1] .

References

1. Lim WA, June CH. The Principles of Engineering Immune Cells to Treat Cancer. Cell. 2017;168(4):724-740. doi:10.1016/j.cell.2017.01.016
2. Speiser DE, Chijioke O, Schaeuble K, Münz C. CD4+ T cells in cancer. Nat Cancer. 2023;4(3):317-329. doi:10.1038/s43018-023-00521-2
3. Serra V, Fiorillo E, Cucca F, Orrù V. Quantifying the Detrimental Effects of Multiple Freeze/Thaw Cycles on Primary Human Lymphocyte Survival and Function. Int J Mol Sci. 2022;24(1):634. doi:10.3390/ijms24010634
4. Olson WC, Smolkin ME, Farris EM, et al. Shipping blood to a central laboratory in multicenter clinical trials: effect of ambient temperature on specimen temperature, and effects of temperature on mononuclear cell yield, viability and immunologic function. J Transl Med. 2011;9(1):26. doi:10.1186/1479-5876-9-26
5. Owen RE, Sinclair E, Emu B, et al. Loss of T cell responses following long-term cryopreservation. J Immunol Methods. 2007;326(1-2):93-115. doi:10.1016/j.jim.2007.07.012
6. Yi PC, Zhuo L, Lin J, Chang C, Goddard A, Yoon OK. Impact of delayed PBMC processing on functional and genomic assays. J Immunol Methods. 2023;519:113514. doi:10.1016/j.jim.2023.113514
7. Agashe C, Chiang D, Grishin A, et al. Impact of granulocyte contamination on PBMC integrity of shipped blood samples: Implications for multi-center studies monitoring regulatory T cells. J Immunol Methods. 2017;449:23-27. doi:10.1016/j.jim.2017.06.004
8. ISBER. Accessed February 16, 2024.
9. Lim WA, June CH. The Principles of Engineering Immune Cells to Treat Cancer. Cell. 2017;168(4):724-740. doi:10.1016/j.cell.2017.01.016
10. Speiser DE, Chijioke O, Schaeuble K, Münz C. CD4+ T cells in cancer. Nat Cancer. 2023;4(3):317-329. doi:10.1038/s43018-023-00521-2
11. Serra V, Fiorillo E, Cucca F, Orrù V. Quantifying the Detrimental Effects of Multiple Freeze/Thaw Cycles on Primary Human Lymphocyte Survival and Function. Int J Mol Sci. 2022;24(1):634. doi:10.3390/ijms24010634
12. Olson WC, Smolkin ME, Farris EM, et al. Shipping blood to a central laboratory in multicenter clinical trials: effect of ambient temperature on specimen temperature, and effects of temperature on mononuclear cell yield, viability and immunologic function. J Transl Med. 2011;9(1):26. doi:10.1186/1479-5876-9-26
13. Owen RE, Sinclair E, Emu B, et al. Loss of T cell responses following long-term cryopreservation. J Immunol Methods. 2007;326(1-2):93-115. doi:10.1016/j.jim.2007.07.012
14. Yi PC, Zhuo L, Lin J, Chang C, Goddard A, Yoon OK. Impact of delayed PBMC processing on functional and genomic assays. J Immunol Methods. 2023;519:113514. doi:10.1016/j.jim.2023.113514
15. Agashe C, Chiang D, Grishin A, et al. Impact of granulocyte contamination on PBMC integrity of shipped blood samples: Implications for multi-center studies monitoring regulatory T cells. J Immunol Methods. 2017;449:23-27. doi:10.1016/j.jim.2017.06.004
16. ISBER. Accessed February 16, 2024. https://isber.org

Haris Choudhery (HC): Talk us through why it’s so important to get PBMC isolation done correctly and what downstream applications it leads to

Jennifer Moore (JM): PBMC isolation is crucial because it enables researchers to separate peripheral blood mononuclear cells (PBMCs) from whole blood, allowing for focused study on these specific cells. Correctly isolating these PBMCs ensures purity and viability, which is essential for downstream applications such as biomarker discovery, drug development, oncology research, and clinical trials. PBMCs serve as valuable indicators of immune response, disease progression, and treatment efficacy in various medical and research contexts. Therefore, accurate isolation of these cells is fundamental to obtaining reliable data as failing to do this can lead to low reproducibility between investigations.

HC: Why might researchers choose to automate PBMC isolation instead of manually isolating them?

JM: Researchers often opt for automated PBMC isolation for several reasons. Firstly, automation streamlines the process, reducing human error and variability inherent in manual isolation techniques. This consistency ensures reproducibility and reliability of results which is critical for research validity. Additionally, automation increases throughput, enabling the processing of larger sample volumes in a shorter time frame, which is advantageous for high-throughput studies or clinical trials. Furthermore, automated systems often offer integrated data management, traceability, and quality control features, enhancing efficiency and compliance with regulatory standards.

HC: What hurdles do researchers face when isolating PBMCs themselves?

JM: Researchers will encounter various challenges when isolating PBMCs if they are unfamiliar with best practices and standard operating procedures. Regarding manual isolation methods, these can be labor-intensive, time-consuming, and prone to inconsistencies, leading to variable outcomes. Achieving high purity and viability of PBMCs consistently requires expertise and experience in handling blood samples and performing centrifugation techniques. Additionally, manual workflows pose risks of contamination and sample mishandling, jeopardizing data integrity and experimental validity. Moreover, manual isolation may not be scalable for studies requiring processing of large sample cohorts, limiting research efficiency and productivity.

HC: How easy or difficult is it to set up automated PBMC isolation in your own labs?

JM: Researchers who are new to automated PBMC isolation may encounter several challenges or hurdles:

• Initial Investment: Acquiring automated PBMC isolation equipment represents a significant upfront capital expenditure for research laboratories, which may pose financial challenges, especially for smaller or resource-constrained institutions.

• Technical Complexity: Operating automated systems requires technical expertise and training. Researchers may face a learning curve in understanding the operation, maintenance, and troubleshooting of the equipment and software.

• Protocol Optimization: Despite being automated, PBMC isolation protocols may still require optimization to ensure optimal performance and yield. Researchers may need to experiment with various parameters to achieve desired results. This may increase turn around times initially while researchers learn how to achieve the desired results.

• Integration with Workflows: Integrating automated PBMC isolation into existing laboratory workflows and processes can be challenging. Researchers need to ensure seamless integration with sample handling, data management, and downstream analysis procedures.

• Quality Control: Maintaining quality control measures is crucial in automated PBMC isolation to ensure consistency and reliability of results. Researchers must establish robust quality control protocols and monitor process parameters effectively.

• Validation and Compliance: Validating automated PBMC isolation protocols and ensuring compliance with regulatory standards are essential but can be time-consuming and complex processes requiring careful documentation and adherence to guidelines.

Overall, while automated PBMC isolation offers numerous benefits, researchers new to this technology must navigate various challenges to maximize its potential and integration into their research workflows.

HC: How does Sampled help researchers who require PBMC isolation? What are the benefits of outsourcing PBMC isolation?

JM: Sampled provides comprehensive PBMC isolation services, offering researchers a range of benefits:

• Expertise: Sampled’s experienced team ensures accurate and reproducible PBMC isolation using well established protocols and state-of-the-art equipment, such as the Hamilton EasyBlood platform, which minimizes variability and ensures reproducibility.

• Efficiency: Outsourcing PBMC isolation to Sampled saves researchers time and resources by eliminating the need for specialized equipment, personnel training, and protocol optimization. This allows researchers to focus on core research activities and accelerate project timelines whilst saving on capital expenditure.

• Quality Assurance: Sampled maintains rigorous quality control measures throughout the isolation process, ensuring high purity and viability of PBMCs for downstream applications. This commitment to quality assurance provides researchers with confidence in the reliability and consistency of their data.

• Scalability: Sampled can meet your changing needs and enables processing of large sample volumes efficiently, catering to diverse research needs and timelines. Whether for small-scale studies or high-throughput projects, Sampled offers flexible solutions to meet researcher requirements.

In summary, outsourcing PBMC isolation to Sampled offers researchers a convenient, reliable, and cost-effective solution, enabling them to obtain high-quality PBMCs for their research endeavors.

If you would like to learn more about our automated PBMC isolation services and the advantages of outsourcing this service, contact one of our experts today

1. Genomic Stability

One of the biggest concerns in iPSC generation is the potential accumulation of genetic mutations, including copy number variations and single nucleotide variants (SNVs). Without meticulous quality control, undetected genetic aberrations may  compromise the genomic stability of iPSCs, leading to unpredictable downstream effects such as tumorigenicity and impaired differentiation potential.

G-band karyotyping should also be carried out to ensure that no chromosomal abnormalities are present, such whole chromosome deletions or duplications. An analysis of the chromosome banding patterns in iPSCs should always be carried out and compared against the banding pattern of a normal cell.

2. Cell Line Purity and Homogeneity

Contamination with residual non-pluripotent cells during reprogramming poses a significant risk to the purity and homogeneity of iPSC populations. In the absence of stringent quality control, the presence of non-pluripotent cells can compromise the validity of experimental results and potentially introduce genetically abnormal cells into an otherwise homogenous population which would lead to clinical applications needing to be halted for safety concerns.

Inadequate quality control can also lead to the persistence of residual reprogramming factors or vectors, such as Sendai reprogramming vectors, which may elicit an immune response upon transplantation into a host. This immunogenicity poses a significant safety concern for iPSC-based therapies. Rigorous quality control is essential to eliminate or minimize the presence of potentially harmful components, ensuring the safety and efficacy of iPSC-derived products in clinical settings.

3. Functional Pluripotency

The ultimate utility of iPSCs lies in their ability to accurately recapitulate the characteristics of embryonic stem cells, including robust pluripotency and the capacity for directed differentiation. Insufficient quality control measures may result in the generation of iPSCs with compromised pluripotency, limiting their differentiation potential and rendering them unsuitable for downstream applications in disease modeling and therapeutic interventions.

Many tests now exist to ensure that newly generated iPSC populations are indeed pluripotent such as confirming expression of stemness markers through FACS analysis. Through FACS, the dual expression of Oct4 and Tra-1-60 (key stem markers) can be confirmed within the cells. Additionally, analysis of pluripotency can be carried out by demonstrating that the cells can form embryoid bodies that contain each of the three germ line layers. Finally, through gene expression arrays, key genes known to be markers of pluripotency can be assayed. 

4. Viability and Sterility

If you are able to generate genetically normal, pluripotent iPSCs without any residual non-pluripotent cells or reprogramming factors, another consideration is the cell population’s viability and sterility. It isn’t enough to be able to generate a few thousand viable iPSCs at a time when millions or billions of cells are required for your research. Likewise, if you haven’t tested your cells for the presence of microbial contamination (including mycoplasma), your iPSCs may be contaminated leading to loss in viability, cell function and genetic abnormalities.

Regulatory agencies, such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), have strict guidelines regarding the quality and safety of cell-based therapies. The presence of mycoplasma contamination in iPSCs violates these regulatory standards, making the cells unsuitable for use in clinical trials.

iPSC Quality Control: Conclusion

In conclusion, the successful harnessing of iPSCs for biomedical applications hinges on the establishment and adherence to stringent quality control measures throughout the generation process. Failure to implement these measures not only jeopardizes the reliability and reproducibility of experimental results but also poses serious safety concerns for the translational use of iPSCs in regenerative medicine.

Sampled’s experts are highly trained at generating iPSCs and carrying out stringent quality control tests to measure pluripotency of newly generated iPSCs as well as ensure they are viable and pure. We understand that not all labs can afford to carry out the necessary quality control procedures they want to, which is why clients work with us to gain peace of mind and save on capital expenditure. To learn more about our iPSC generation services, contact one of our experts today

Who are NINDS?

The National Institute of Neurological Disorders and Stroke (NINDS) was established in 1950 and is a part of the US National Institutes of Health (NIH). Its mission is to seek fundamental knowledge about the brain and nervous system to reduce the burden of neurological disease for all people.

NINDS aims to provide tools and funding for research into neurological disorders that cause a considerable burden on individuals, families, and communities. NINDS research funding has already led to the development of precise diagnostic tools and new treatment interventions for many neurological conditions. The institute also invests heavily in educating the general public and medical practitioners on the signs and symptoms of neurological disorders and stroke.

One of NINDS’ critical projects is the extensive collection and storage of human cells that can be requested for research purposes. This extensive collection of cells come from a large population of donors including men, women and children of all wide and diverse range of backgrounds. The repository of biomaterials is not restricted to researchers based in the US and can be requested by small academic groups through to large biotechnology and pharmaceutical companies.

NINDS Human Cell and Data Repository (NHCDR)

The NHCDR hosts over 400 subjects that can be requested for research purposes. These subjects are sourced from a wide array of hosts and can be filtered for by gender, age, race and cell type (iPSCs, edited iPSCs or Fibroblasts). Subjects can also be selected based on the disease type, of which there are 14 to choose from including:

• Alzheimer’s disease
• Amyotrophic Lateral Sclerosis
• Ataxia-Telangiectasia
• Dystonia
• Frontotemporal Degeneration
• Huntington’s Disease
• Lewy Body Dementia
• Mild cognitive impairment
• Myotonic Dystrophy
• Parkinson’s Disease
• Parkonsonism
• Spinal Muscular Atrophy
• Spinal-Bulbar Muscular Atrophy
• Spinocerebellar Ataxia
• Control samples

A full comprehensive list of subjects held by NINDS can be found on their website. If you wish to query or request cell samples, an easy “how to order” guide can be found here. Once a Material Transfer Agreement form is completed (found on NINDS website here), researchers can search for the cells they require and purchase up to a maximum of 10 vials.

NINDS impact on research

The NHCDR has supported a diverse array of stem cells-based research, from studies of the basic biology of stem cells in the developing and adult mammalian brain, to studies focusing on nervous system disorders such as ALS or spinal cord injury. Other examples of research include using induced pluripotent stem cells (iPSCs) to derive dopamine-producing neurons that might alleviate symptoms in patients with Parkinson’s disease and using embryonic stem cells to generate cerebral organoids to model Zika virus infection.

Since the NINDS repository was established, countless papers have been published that have credited the organization for providing the biomaterial in their investigations. Many of the papers crediting NINDS for providing the biomaterial utilized in their investigations include high impact factor journals such as

• Nature
• Cell Stem Cell
• Molecular Cell
• Neuron
• Science Translational Medicine

Requesting cells from Sampled

Sampled is proud to be the sole distributor for the NHCDR. Although NINDS is based in the US, the biomaterials can be requested by scientists worldwide by small academic groups to large pharmaceutical organizations. Requesting cells from the NHCDR is a straightforward process, researchers can contact us directly through our website here, to speak to one of experts. We are here to help researchers, which is why we also have a step by step guide to ordering cells from the NHCDR.

The benefits of working with iPSC Reprogramming Services

A major advantage of working with human iPSCs, compared to pluripotent embryonic stem cells, is that these cells have a known phenotype, unlike pluripotent cells from embryos in which the phenotype is unknown.

Similar to human embryonic stem cells (hESCs), iPSCs can be generated and used as a cellular tool to unravel mechanisms of human development and to model diseases in a manner not possible before given that many of these diseases do not occur until later in life. iPSCs also provide a human model system, which is important to consider as certain disease models such as Alzheimer’s disease cannot be accurately replicated in animal models.

Besides these fundamental aspects of human biology and physiology that are revealed using iPSC or iPSC-derived cells, these cells hold an immense potential for cell-based therapies, and for the discovery of new or personalized pharmacological treatments for many disorders. An additional advantage is that many of the ethical concerns around the derivation of hESCs are not applicable to the derivation of iPSCs. 

What are the advantages of outsourcing the reprogramming of adult cells into iPSCs?

1. Our iPSC Reprogramming experts are your experts

One of the key advantages of using an iPSC reprogramming services, such as those offered by Sampled, is the convenience it offers. Before even working with the cells, researching the protocols, best practices and reagents required for efficient and reliable iPSC reprogramming can be a time-consuming and costly process.

By outsourcing this work to a service provider such as Sampled, researchers can access the latest reprogramming iPSC protocols and technologies, which ensures a higher level of efficiency and accuracy in the reprogramming process. We know that reprogramming protocols are long and laborious, and that one simple error can set back researchers by weeks. By outsourcing cell reprogramming, you can stay one step ahead by focusing on the work that matters most and not wasting any time on experiments that fail due to insufficient expertise or knowledge.

2. Quality control that is tailored to meet your needs

By outsourcing iPSC reprogramming services, you are able to tailor the quality control tests in order to get exactly what you need. At Sampled our human iPSC generation service come with several quality control tests as standard. Every cell undergoes rigorous testing to ensure their quality and consistency:

• Sterility testing including mycoplasma
• Cell identity confirmation using 96 SNP Fluidigm Panel
• Post thaw viability
• Expression of stemness markers through FACS analysis of the dual expression of Oct4 and Tra-1-60

This gives researchers confidence in the cells they are using and provides them with a reliable source of cells for their research. Furthermore, we offer bespoke quality control options that include:

• Analysis of pluripotency through Scorecard: Demonstration of pluripotency using in vitro assays such as embryoid body formation
• Analysis of pluripotency through Pluritest: Demonstration of stemness using a gene expression array
• Reprogramming factor persistence assays that ensure the loss of exogenous reprogramming factors
• Assessment of iPSC genomic stability by G-banded karyotyping

3. Save on capital expenditure

Outsourcing iPSC reprogramming services can provide significant cost savings. As mentioned earlier, setting up and maintaining an efficient iPSC reprogramming protocol requires a considerable investment in time and resources. Hiring and maintaining staff members to grow, maintain and reprogram cells is an expensive venture which becomes more costly when the cost of reagents and equipment is also added.  By outsourcing to a service that specializes in iPSC generation, researchers can also save money from not having wasted reagents and cells on failed attempts to reprogram them. This cost-saving can be particularly beneficial for small to medium-sized enterprises, as well as academic institutions with limited budgets.

4. Saving time

Meeting deadlines is a priority for every business regardless of its size, which is why outsourcing to a service provider that can generate iPSCs is a powerful reason why researchers are turning to Sampled for iPSC reprogramming services. Instead of trying and failing to reprogram cells over and over again, which inevitably pushes back deadlines, outsourcing gives researchers peace of mind that their iPSCs will arrive on time and is exactly what they need to conduct their investigations. Moreover, outsourcing to a service provider allows researchers to scale up their research without worrying about expanding their lab space, head count or costs associated with purchasing more resources.

In summary, outsourcing iPSC reprogramming services from cells to iPSCs could offer numerous advantages compared to reprogramming iPSCs in house. It saves time, provides access to highly-characterized human iPSCs, produces cells of higher quality, and can provide significant cost savings. Consequently, more organizations and researchers are turning to iPSC generation services to take advantage of these benefits.

To learn more about how our iPSC reprogramming services work, talk to an expert today

NPC Differentiation applications can be vast, and could revolutionize treatment of neurological diseases – but why outsource it?

Neural progenitor cells (NPCs) are a type of multipotent, adult stem cell that possess the ability to differentiate into neural cells. NPCs differentiate into the glial and neural cell types that populate the central nervous system (CNS). It is for this reason that they are highly sought after in such fields as drug discovery, disease modelling, studying neurodevelopment and regenerative medicine.

One of the biggest potential goals of NPC differentiation is in the development of cell therapy for various neurological disorders. NPC differentiation has been shown to improve neurological function in animal models of Parkinson’s disease, spinal cord injury, and stroke. Researchers are now exploring potential therapeutic applications for NPCs in humans, which could lead to significant advancements in the treatment of these conditions. Similarly, pharmaceutical companies are now actively utilizing NPCs is in drug discovery and development.

With the ability to produce neurons and glial cells, NPC Differentitation can be used to study the effects of drugs on the nervous system as well as study the risk of toxicity to ensure patient safety. This can help researchers identify potential drug candidates and optimize their efficacy and safety profiles.

With such promise, the question arises: should researchers create their own iPSCs before differentiating them into NPCs? Briefly, iPSCs are pluripotent stem cell that can be generated from adult cells, such as fibroblasts or blood cells, and reprogrammed to their pluripotent or “blank” state. This makes them an attractive source of NPCs, however, depending on the methods used this can be very laborious in terms of time and resources. In most reprogramming protocols, a single mistake or misstep in following the protocol can lead to weeks of cell culture work being wasted, not to mention the loss in cell culture reagents.

In this article we will explore 4 reasons why outsourcing NPC differentiation is advantageous to researchers:

Reducing expenditure and resources

Outsourcing iPSC differentiation can save time and resources for researchers, who may not have the necessary expertise or infrastructure to perform the complex differentiation process in-house. This allows them to focus on their core research, such as drug discovery and preclinical testing. Additionally, outsourcing can provide access to a diverse range of iPSC lines and NPCs, which can be custom designed to meet specific research needs such as the NINDS Stem Cell Catalog.

Instead of hiring new employees who have the ability to reprogram patient cells into iPSCs and differentiate them into NPCs, Sampled can take patient samples and do the work for you, saving you time and money by removing the need to hire new staff members and training them.

Consistency and Quality of NPCs

Another advantage of outsourcing is that it can ensure the quality and consistency of NPCs. Differentiation of iPSCs into NPCs is a labor-intensive process that requires strict quality control measures to ensure that the NPCs are of the desired purity and functionality, this process takes even longer if you do not have the right training or expertise. Our in-house experts are equipped with the right knowledge and tools to be able to carry out reprogramming and differentiation for you.

Outsourcing to a specialized service provider can offer access to experts with experience in the differentiation process and quality control measures, ensuring that the NPCs are of high quality and consistent across batches. To learn more about our quality control options you can read our resource on Source and Stem cell reprogramming services.

Reducing turn around time

As mentioned above, differentiation of iPSCs into NPCs is a time and labor-intensive process. This is especially true if you are new to cell culture work or differentiating iPSCs, as a single mistake can cost you months of time as you are forced to restart your differentiation protocol. At Sampled we can provide up to 10 individual cell lines within 3-4 months where researchers will receive 16-20 vials containing 2 x 10⁶ cells per vial.

Scaling NPC Differentiation Efficiently

Projects can change direction at a moment’s notice. We understand the need to stay agile which is why outsourcing iPSC differentiation into NPCs can benefit researchers who need to scale up their research. We work with you to understand your needs and requirements and aid in experimental design where necessary to ensure that you receive the right number of NPCs that have undergone the appropriate quality control measures

In conclusion, the applications of NPC Differentiation are vast and can potentially revolutionize the treatment of neurological disorders. Outsourcing iPSC differentiation into NPCs can offer several advantages, including cost and time savings, access to specialized expertise, and quality control measures. This can enable researchers and biopharmaceutical companies to accelerate their drug discovery and development programs, providing potential new treatments and hope for patients suffering from neurological disorders.

The NINDS biobank stem cell collection currently contains 411 subjects, 169 of which have iPSC and 270 of which have fibroblasts and represents several neurodegenerative disorders, including (but not limited to):

• Alzheimer’s disease
• Amyotrophic Lateral Sclerosis
• Frontotemporal Degeneration
• Huntington’s disease
• Parkinson’s disease

If you would like to browse and order cell lines, first go to: https://stemcells.nindsgenetics.org/ and follow the instructions below:

Creating a signed Material Transfer Agreement (MTA)

A key requirement for ordering lines is ensuring a signed MTA is in place.

The MTA forms can be found in the Documents section of the catalog application as shown below.

Selecting cell lines

1. Once you have downloaded the correct MTA form, select the Subjects tab and choose subjects of interest using the filters to narrow by disease, etc, if necessary

Locate the desired cell lines in the subject’s detail view, clicking anywhere within the row will bring up the cell line’s details.

If the subject has cell lines, such as iPSCs and Fibroblasts, they will be displayed in the subject’s detail view. These are found at the bottom of the Full Record tab, and also the Cell Lines tab. Click the Add to Cart button for the desired lines.

Purchasing cell lines

2. Once you have selected the cell line, scroll down and Click Add to Cart.

3. You can then click on the up and down arrows to specify how many vials you would like to purchase (the maximum is 10):

4. Go to the cart and click Checkout.

5. Enter the required fields and upload the required documents, such as signed MTAs (found in the Documents section) and Statement of research intent (SRI).

6. Once all relevant information has been filled in, Click Submit Order 

7. You will receive an e-mail summarizing your order and requesting e-mail address verification.

Here is an example of the e-mail you will receive. Click the link to verify your email address and your order should be all set.

Cell and Data Repository infographic

Download our infographic

View further details on our catalog of the NINDS Human Cell and Data Repository, including a breakdown of gender, race and clinical affected status of cell and disease types.

View infographic

If you need any help ordering from the NINDS website, you can contact us at NINDS@sampled.com and one of our experts will be happy to help.

You can also view our other cellular services here.

How does CRISPR gene editing work?

When CRISPR Cas9 protein is added to a cell, along with a strand of guide RNA, the Cas9 protein first binds to the guide RNA. This complex is then able to move along the DNA sequence until it locates a specific sequence of DNA (approximately 20 base pairs long) that matches the guide RNA. Once the complex locates the specific sequence or gene it was programmed to, it cuts the DNA before mutations are introduced to make precise changes to the DNA sequence. This can include removing the sequence or turning the genes on/off by changing the one letter of the DNA code to another.  

The promise of CRISPR technology is very exciting as the technology opens doors for groundbreaking changes to everyday life, including the prevention and treatment of many diseases, increasing crop yield and even editing out harmful genes within the DNA of fetuses.

So, what are the benefits of outsourcing CRISPR gene editing?

While some research institutions have developed in-house expertise in CRISPR gene editing, there are several compelling reasons why outsourcing these services can be beneficial. In this blog, we will explore some of the five reasons why outsourcing CRISPR gene editing services can be advantageous.

Access to specialized expertise

CRISPR gene editing is a complex and rapidly evolving technology that requires specialized expertise to execute with precision and accuracy. With CRISPR being a new technology, there is a lack of user friendly guides or resources to help researchers who wish to carry out CRISPR by themselves. This has led to scientists who are unfamiliar with protocols attempting their experiments several times before achieving some success, with many citing that the optimization step is particularly difficult to execute properly. The success achieved by the few who have managed to delete/insert genes is limited however, as editing efficiency is far lower than they would hope.

By repeating the same experiment several times, only to obtain low editing efficiency, researchers who have tried to execute CRISPR research are wasting not only time and resources but money too. Outsourcing gene editing services to a specialized service provider such as Sampled allows researchers to gain access to a team of experienced and knowledgeable experts with deep expertise in this field. We  are equipped with the latest gene editing tools and technologies, allowing us to deliver efficient and effective solutions for a wide range of gene editing applications.

Cost-effective solution

Outsourcing CRISPR gene editing services can be a cost-effective solution for research institutions and biotech companies. The cost of setting up an in-house gene editing laboratory can be high, as it requires significant investments in equipment, personnel, and training which can take a long time. By outsourcing gene editing services, institutions and companies can save on these costs and leverage the expertise of specialized service providers who have already made these investments.

Flexibility and scalability

Outsourcing CRISPR gene editing services to Sampled offers flexibility and scalability. We can quickly adapt to your project needs and timelines changing, providing researchers with the ability to scale up or down their gene editing projects as required. This flexibility can be particularly valuable in situations where resources are limited or where project timelines are subject to change.

Quality assurance

Outsourcing gene editing services can also provide researchers with quality assurance and peace of mind. Our tried and tested established protocols and quality control processes are in place to ensure that all gene editing projects are executed to the highest standards of accuracy, efficiency, and safety. By outsourcing gene editing services, researchers can be confident that their gene editing projects will be executed to the highest standards, providing reliable and reproducible results.

Regulatory compliance

CRISPR gene editing is subject to stringent regulatory compliance requirements, particularly when it comes to clinical trial research. By outsourcing gene editing services to a service provider that specializes in regulatory compliance, researchers can ensure that their projects meet all regulatory requirements and standards which in turn ensures your project won’t suffer delays. This can be particularly important for researchers seeking to develop new gene therapies or other clinical applications of CRISPR gene editing.

The benefits of outsourcing CRISPR gene editing work to Sampled

We accept induced pluripotent stem cells (iPSCs) directly from clients or those selected from repositories housed at Sampled such as National Institute of Mental Health (NIMH; https://www.nimhgenetics.org/) and the National Institute of Neurological Disorders and Stroke (NINDS; https://stemcells.nindsgenetics.org/). Our trained experts can discuss your needs and help with experimental design so that you can be assured that the cells to be edited meet your expectations. Furthermore, our cells undergo rigorous quality control testing to ensure that you will receive a 100% homogeneous population, this is crucial for investigations such as drug screening studies to minimize noise and prevent genetic drift within cell populations.

To summarize, outsourcing CRISPR gene editing services can provide many benefits to research institutions and biotech companies. By gaining access to specialized expertise, cost-effective solutions, flexibility, quality assurance, and regulatory compliance, researchers can execute their gene editing projects with confidence and achieve their desired outcomes, without having to become CRISPR experts overnight.

To get in touch with our experts and learn more about our Sampled Labs Services click here.