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> Insights > Accelerate PSC Derived Neuron Differentiation with Universal Laminin 521/511 & Complementary Growth Factors 
Parkinson's disease, a prevalent neurodegenerative disorder, affects approximately 1% of the population aged 60 and above, with the number of cases expected to double by 2040, posing a growing global health burden. The disease primarily targets dopaminergic neurons in the substantia nigra of the brain, causing a progressive decline in dopamine production. This neurotransmitter deficit manifests as characteristic motor symptoms, including tremors, bradykinesia, and postural instability. Current treatments mainly rely on medications like levodopa to replenish dopamine levels or mimic its function, offering temporary symptomatic relief but failing to halt disease progression. Deep brain stimulation, an invasive surgical option, modulates neural activity but is not suitable for all patients.
Stem cells have emerged as a highly promising approach for treating Parkinson's disease, offering the potential to not only alleviate symptoms but also address the root cause of the disease by replacing the lost dopaminergic neurons. Embryonic stem cells (ES) and induced pluripotent stem cells (iPSCs) are of particular interest due to their remarkable ability to differentiate into various cell types, including dopaminergic neurons. Through a carefully controlled process of differentiation, these stem cells can be guided to develop into functional neurons that can integrate into the existing neural circuitry, secrete dopamine, and restore normal neural communication. BlueRock Therapeutics has made significant strides in this field with its lead candidate, bemdaneprocel (BRT - DA01), which is derived from pluripotent stem cells. In preclinical and early - stage clinical studies, BRT - DA01 has demonstrated good tolerability and the ability to integrate into the host brain tissue, leading to the restoration of dopamine - producing cells. Encouraged by these results, the company is set to advance BRT - DA01 into Phase III trials, bringing hope for a more effective and long - lasting treatment for Parkinson's patients. Aspen Neuroscience is another notable player in the stem cell therapy arena for Parkinson's disease. Their approach involves using autologous iPSCs, which are reprogrammed from the patient's own cells, reducing the risk of immune rejection. Aspen's research focuses on differentiating these autologous iPSCs into dopaminergic neurons and transplanting them into the patient's brain, aiming to provide a personalized and safe treatment option. Their ongoing clinical trials are closely monitored, and initial data show promising signs of cell survival and potential functional improvement.
Figure. Overview of GMP manufacturing of stem cell derived dopamine progenitor cell products.
(Cited by 2023. Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson’s disease, STEM-PD. Cell Stem Cell)
Despite the great potential of stem cell therapies for Parkinson's disease, several significant challenges need to be overcome before they can become widely available. One of the major hurdles lies in the large - scale production of high - quality, functional dopaminergic neurons from stem cells while maintaining consistency in cell quality and characteristics. When it comes to the expansion of iPSCs, maintaining their pluripotency and genomic stability over the long term is of utmost importance. Pluripotency allows iPSCs to differentiate into any cell type in the body, and genomic stability ensures that the cells do not accumulate harmful mutations during the expansion process. High quality Laminin protein, a major component of the extracellular matrix, plays a pivotal role in this regard. Laminin interacts with specific receptors on the surface of stem cells, initiating a series of intracellular signaling cascades that are essential for the self - renewal of the cells. In traditional culture systems, feeder cells or complex matrices are often used to support the growth of iPSCs. However, these methods can introduce variability in cell growth and differentiation, making it difficult to scale up the production process. To address this, researchers are actively exploring defined, xeno - free culture media and advanced bioreactor systems that incorporate high quality Laminin protein. These systems are designed to precisely control environmental factors such as nutrient supply, oxygen tension, and shear stress, creating an optimal environment for the expansion of iPSCs. Nevertheless, even with these advancements, genetic alterations can still occur during prolonged cell culture, potentially leading to genomic instability. Advanced gene - editing techniques like CRISPR - Cas9 offer the possibility of correcting or preventing genetic mutations, but concerns regarding off-target effects, which may lead to unintended genetic changes, and ethical considerations surrounding the modification of human genes remain major obstacles.
Another critical challenge is increasing the yield and efficiency of iPSC differentiation into neural cells. The current differentiation protocols are often complex, time - consuming, and result in relatively low yields of functional neurons. The process of guiding iPSCs to differentiate into dopaminergic neurons involves multiple sequential steps, each requiring precise control of various signaling pathways. Key factors such as FGF8b (fibroblast growth factor 8b) and SHH (sonic hedgehog) play crucial roles in inducing neural differentiation. FGF8b activates specific signaling pathways during the early stages of differentiation, guiding the iPSCs towards a neural lineage. SHH, on the other hand, is essential for the subsequent specification and maturation of dopaminergic neurons. Researchers are constantly working on optimizing these differentiation protocols, exploring the use of different combinations of cytokines, growth factors, and small molecules to enhance the efficiency of the process. Additionally, 3D culture systems have shown great potential in improving the differentiation of iPSCs into neural cells. These systems can better mimic the in - vivo microenvironment, promoting more efficient cell - cell and cell - matrix interactions, which in turn can lead to the production of higher - quality and greater quantities of differentiated neural cells. However, scaling these optimized protocols to industrial levels while maintaining strict quality control remains a significant challenge. Ensuring the consistency and reproducibility of the differentiation process across large - scale production is essential to guarantee the safety and efficacy of stem cell - based treatments for Parkinson's disease.
Fortunately, ACRO offers a complete solution for differentiating iPSCs into neurons, providing hope for overcoming these hurdles and making stem cell - based treatments for Parkinson's more accessible.
GMP-grade cytokines support the creation of neuronal cultures from hiPSC, originating from a patient for the use in neurological disorders, has received wide attention for the potential to create translatable disease-in-dish models.
•Laminin 521(Cat. No. GMP-LA5H24) & Laminin 511(Cat. No. GMP-LA1H25):
Available in both PG and GMP grades, these universal ECM reagents are essential for consistent hPSC expansion and neuron differentiation. In our internal verification, GMP grade Laminin 521 or Laminin 511 could support hPSC expansion and stemness (about 99% OCT4+SOX2+SSEA4+) after passage 10. And they could also support neuronal progenitor cell (NPC) differentiation (about 99% purity with PAX1+SOX2+Nestin+ expression after 7 days differentiation) and dopaminergic neuron formation (about 95% purity with TH1+MAP2+ expression). Moreover, our bulk GMP Laminin protein (>=10mg) will reduce at least 30%-50% cost in your manufacturing process. Our GMP Laminin protein have already been widely used in PSC banking and differentiation process.
•Differentiation Factors (Cat. No. GMP-FGBH16, SH7-H5116, BDF-H5219, GDF-H5118):
The first GMP grade FGF8b in the world;
• The combination of GMP grade FGF8b and Noggin, Shh, BDNF and GDNF could highly support dopaminergic neuron differentiation (about 95% purity with TH1+MAP2+). And they also have high batch-to-batch consistency and stability based on Stringent quality control tests.
As a globally recognized, regulation - compliant supplier, we adhere to all international legal and regulatory standards, ensuring seamless integration into your manufacturing processes. Moreover, we offer a complete range of customizable services to meet your specific requirements, providing comprehensive support to overcome every challenge in stem cell therapy and drive the success of your projects.
• Shh and Noggin for iPSC derived NPC differentiation
Human Sonic Hedgehog (C24II) Protein, premium grade (Cat. No. SH7-H5116) and Human Noggin Protein, premium grade (Cat. No. NON-H5219) could significantly induce iPSC derived NPC differentiation coating with GMP Human Laminin 521 Protein (Cat. No. GMP-LA5H24), with high expression of NPC markers (PAX6, SOX1, NESTIN) by immunofluorescence.
Human Sonic Hedgehog (C24II) Protein, premium grade (Cat. No. SH7-H5116) and Human Noggin Protein, premium grade (Cat. No. NON-H5219) could significantly induce iPSC derived NPC differentiation coating with GMP Human Laminin 521 Protein (Cat. No. GMP-LA5H24), with high expression of NPC markers (PAX6, SOX1, NESTIN) by FACS.
• Shh and FGF-8b for dopaminergic neurons differentiation
GMP Human FGF-8b Protein (Cat. No. GMP-FGBH16) and Human Sonic Hedgehog (C24II) Protein, premium grade (Cat. No. SH7-H5116) could efficiently induce the neuron progenitor cell into dopaminergic neurons differentiation, highly expressed TH1 and MAP2 in immunofluorescence staining and FACS (Routinely tested).
GMP Human FGF-8b Protein (Cat. No. GMP-FGBH16) and Human FGF-8b Protein, premium grade (Cat. No. FGB-H5115) have similar bioactivity to efficiently induce the neuron progenitor cell into dopaminergic neurons differentiation, highly expressed TH1 and MAP2 in immunofluorescence staining and FACS (Routinely tested).
| Catalog No. | Molecule | Product Description |
|---|---|---|
| GMP-FGBH16 | FGF-8b | GMP Human FGF-8b Protein Hot |
| GMP-TG1H25 | TGF-beta 1 | GMP Human TGF-Beta 1 / TGFB1 Protein |
| SH7-H5116 | Sonic Hedgeho | Human Sonic Hedgehog / Shh (C24II) Protein, premium grade |
| NON-H5219 | Noggin | Human Noggin Protein, premium grade |
| BDF-H5219 | BDNF | Human BDNF / Abrineurin Protein (HEK293), premium grade |
| GDF-H5219 | GDNF | Human GDNF / ATF / hGDNF Protein, premium grade |
| GMP-LA5H24 | Laminin 521 | GMP Human Laminin 521 Protein |
| GMP-LA1H25 | Laminin 511 | GMP Human Laminin 511 Protein |
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