SINGAPORE AND INDIA – Through a collaborative partnership between Stempeutics Research, India, and Esco Aster, Singapore, the first study to demonstrate the success of macrocarrier-based Tide Motion system for human bone marrow mesenchymal stromal cells (hBM-MSCs) expansion has been recently published in the peer-reviewed Biotechnology Journal.
Mesenchymal stromal cell (MSC) expansion has evoked great expectations in the scientific community due to its promising potential to be a turning point in modern medicine. With its ease of expansion and low immunogenicity, allogeneic MSC-based interventions are now under several clinical trials as a treatment option for various conditions including treating patients with Acute Respiratory Distress Syndrome (ARDS) caused by pneumonia due to COVID-19. Scale-up manufacturing is necessary to cater to the number of effective doses required for clinical trials and also for commercialization. However, expansion using conventional 2D culture systems not only limits the large-scale expansion of MSC required for commercial manufacturing, but also for making MSC therapies affordable. Other systems developed for larger cultures are facing constraints in terms of their potential to scale up adherent MSCs, in reducing shear stress that may damage these cells, and in the monitoring and controlling culture conditions.
“This collaborative study between Stempeutics and Esco has demonstrated the potential to overcome the limitations of 2D systems using the linearly scalable, extremely low shear stress BioNOC™ II macrocarrier-based Tide Motion technology,” said Xiangliang Lin, CEO, and President of Esco Aster.
In this new peer-reviewed paper, it has been demonstrated that hBM-MSCs could be grown in Esco Aster’s BioNOC™ II macrocarriers in a proof-of-concept (POC) small-scale system and harvested within 11-12 days about 300 million cells in a 0.1L packed bed CelCradle™ Tide Motion bioreactor. Cell expansion amounting to a 60-fold increase from seeding density demonstrates macrocarrier-based Tide Motion system suitability for scale-up. It was also demonstrated in this study the feasibility of the system and macrocarriers to culture hBM-MSCs in serum-free media. Furthermore, growth in macrocarriers retained the phenotypic and potency characteristics of MSCs after confirmation of surface marker expression, differentiation potential, and surrogate vascular endothelial growth factor (VEGF) secretion.
“The results of this study indicate the feasibility and ease of macrocarriers coupled with the Tide Motion system to scale up adherent MSC culture from small scale (isolated and grown initially in serum media) to larger-scale bioreactors using the same packed bed macrocarriers grown in serum-free culture media. The same culture condition and setup can be applied to larger BioNOC™ II packed bed volume (1-300L) of TideXcell® bioreactor, which features a monitoring system, and a closed and automated harvesting system” said Prof. Raviraja NS, Scientific Advisor for Stempeutics and Esco Aster.
“This research is part of a broader effort to commercialize stem cell therapies which have shown promising results from recent clinical trials. Further studies are still being conducted in collaboration to optimize specifically downstream and harvesting to increase the yield harvested while retaining MSCs characteristics”, said Mr. B N Manohar, MD, and CEO of Stempeutics Research.
Esco Aster provides process development with our patented tide motion bioreactors to develop a large scale manufacturing process to produce sufficient doses for clinical trials and meet market demands.
Esco Aster Pte Ltd is a contract development and manufacturing organization (CDMO) founded and deeply rooted by scientists enabling fellow scientists to translate their benchwork into life-saving diagnostics, medicines, therapies, cosmeceuticals, and cellular agriculture at affordable prices for self-sufficiency of the country. Esco Aster Singapore Manufacturing Pte Ltd is our manufacturing arm to provide scale-up and commercial production services for drug substances, drug products, and advanced therapy medicinal products. Esco Aster uses its Tide Motion system for the culture of adherent or anchorage-dependent cells. The system’s applications include cell banking, cell culture-based vaccine production, biologics production, cell therapy, gene therapy, and diagnostics. The name “Tide Motion” derives from the cyclical low and high tides experienced by bodies of water on earth. Similarly, Tide Motion uses a gentle upward and downward liquid flow to provide alternate oxygen and nutrients to the adherent cells in culture. This gentle vertical oscillation of the culture medium creates a dynamic interface between air and culture medium on the surface of the cells. It creates an environment of extremely low shear stress, high aeration and nutrition levels, low to no foaming, and no oxygen limitation. This efficient nutrient and oxygen transfer is what allows the Tide Motion system to produce high-density cell yields. Learn more at www.escoaster.com and connect with Esco Aster on LinkedIn.
Stempeutics is a leading regenerative medicine company in India with a stem-cell platform technology developing treatment of cardiovascular, immune-mediated, and degenerative diseases. It was founded by Manipal Education and Medical Group (MEMG) in 2006 and later entered into strategic alliances with Cipla in 2009 and with Kemwell in 2019. Stempeutics’ strength lies in developing innovative stem cell products by nurturing cutting-edge research and clinical applications through the dedicated efforts of its highly qualified team. Its goal is to develop novel stem cell drugs addressing major unmet medical needs with India’s first global next approach. In 2020, the Drug Controller General of India (DCGI) granted marketing approval of Stempeucel® product for the treatment of Critical Limb Ischemia (CLI). Stempeutics is the only Indian bio-pharma company, holding marketing authorization for Cell Therapy products for Critical Limb Ischemia management. It also has two products in the Phase 3 stage. For more information please visit www.stempeutics.com
Bhat, S., Chiew, G. G. Y., Ng, J. X., Lin, X., & Seetharam, R. N. (2021). Optimization of culture conditions for human bone marrow‐derived mesenchymal stromal cell expansion in macrocarrier‐based Tide Motion system. Biotechnology Journal, e2000540. https://doi.org/10.1002/biot.202000540