Challenges and Solutions for Commercial Scale Manufacturing of Allogeneic Pluripotent Stem Cell Products

Lee, Brian; Borys, Breanna S.; Kallos, Michael S.; Rodrigues, Carlos Alberto Chirano; Silva, Teresa P

doi:10.3390/bioengineering7020031

Cited by 15 publications

(14 citation statements)

References 27 publications

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“…The combination of cell expansion technologies and diverse differentiation protocols has opened the door for creating human-scale, organ-specific cell sources. While these systems have established cell expansion technologies to generate cell quantities sufficient for repopulating humansized organs, the increase in cell numbers begets a more complex microenvironment, which poses a risk of spontaneous differentiation, hindering expansion and directed differentiation capacity [Lee et al, 2020].…”

Section: Bioreactors For Scaling Up Cell Expansion Systemsmentioning

confidence: 99%

Whole Heart Engineering: Advances and Challenges

Morrissey¹,

Mesquita²,

Hochman‐Mendez³

et al. 2021

Cells Tissues Organs

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Bioengineering a solid organ for organ replacement is a growing endeavor in regenerative medicine. Our approach – recellularization of a decellularized cadaveric organ scaffold with human cells – is currently the most promising approach to building a complex solid vascularized organ to be utilized in vivo, which remains the major unmet need and a key challenge. The 2008 publication of perfusion-based decellularization and partial recellularization of a rat heart revolutionized the tissue engineering field by showing that it was feasible to rebuild an organ using a decellularized extracellular matrix scaffold. Toward the goal of clinical translation of bioengineered tissues and organs, there is increasing recognition of the underlying need to better integrate basic science domains and industry. From the perspective of a research group focusing on whole heart engineering, we discuss the current approaches and advances in whole organ engineering research as they relate to this multidisciplinary field’s 3 major pillars: organ scaffolds, large numbers of cells, and biomimetic bioreactor systems. The success of whole organ engineering will require optimization of protocols to produce biologically-active scaffolds for multiple organ systems, and further technological innovation both to produce the massive quantities of high-quality cells needed for recellularization and to engineer a bioreactor with physiologic stimuli to recapitulate organ function. Also discussed are the challenges to building an implantable vascularized solid organ.

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Section: Bioreactors For Scaling Up Cell Expansion Systemsmentioning

confidence: 99%

Whole Heart Engineering: Advances and Challenges

Morrissey¹,

Mesquita²,

Hochman‐Mendez³

et al. 2021

Cells Tissues Organs

View full text Add to dashboard Cite

show abstract

“…Based on the established suspension culture system in 48-well plates, we intended to develop the method to differentiate hESCs into β-like cells in 48-well plates. The diameter of cell aggregates affects mass transfer efficiency and therefore influences differentiation efficiency [26]. Hence, H9 cells at three different densities were initially adopted in this study, including 9 × 10 4 cells/mL, 1.8 × 10 5 cells/mL and 5.4 × 10 5 cells/mL, respectively.…”

Section: Effect Of Cell Density On the Pancreatic Differentiation Efficiency From H9 Cells In 48-well Platesmentioning

confidence: 99%

Development of a 48-Well Dynamic Suspension Culture System for Pancreatic Differentiation from Human Embryonic Stem Cells

Song

Chen²,

Liang³

et al. 2021

Stem Cell Rev and Rep

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Background Human pluripotent stem cells (hPSCs) have started to emerge as a potential tool with application in fields of drug discovery, disease modelling and cell therapy. A variety of protocols for culturing and differentiating pluripotent stem cells into pancreatic β like cells have been published. However, small-scale dynamic suspension culture systems, which could be applied toward systematically optimizing production strategies for cell replacement therapies to accelerate the pace of their discovery and development toward the clinic, are overlooked. Methods Human embryonic stem cell (hESC) line H9 was used to establish the novel 48-well dynamic suspension culture system. The effects of various rotational speeds and culture medium volumes on cell morphology, cell proliferation, cell viability and cell phenotype were evaluated. Effect of cell density on the pancreatic differentiation efficiency from H9 cells in 48-well plates was further investigated. In vitro the function of pancreatic β like cells was assessed by measuring glucosestimulated insulin secretion. Main Results A 48-well dynamic suspension culture system for hESC expansion as cell aggregates was developed. With optimized rotational speed and culture medium volume, hESCs maintained normal karyotype, viability and pluripotency. Furthermore, the system can also support the hESC aggregates subsequent differentiation into functional pancreatic β like cells after optimizing initial cell seeding density. Conclusion A controllable 48-well suspension culture system in microplates for hESCs maintenance, expansion and pancreatic differentiation was developed, which may provide an efficient platform for high-throughput drug screening.

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“…The latter has shown a promising effect when injected in a burn model, in terms of healing and new vessel formation [ 54 ]. However, allogenic cells are less likely to reach the clinic due to several technical challenges, including production in enough numbers, standardization of production and characterization and unexpected immunological events [ 55 ].…”

Section: Reviewmentioning

confidence: 99%

Vascularization is the next challenge for skin tissue engineering as a solution for burn management

et al. 2020

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Skin regeneration represents a promising line of management for patients with skin loss, including burn victims. The current approach of spraying single cells over the defective areas results in variable success rates in different centers. The modern approach is to synthesize a multilayer skin construct that is based on autologous stem cells. One of the main complications with different types of transplants is sloughing due to the absence of proper vascularization. Ensuring proper vascularization will be crucial for the integration of skin constructs with the surrounding tissues. Combination of the right cells with scaffolds of proper physico-chemical properties, vascularization can be markedly enhanced. The material effect, pore size and adsorption of certain proteins, as well as the application of appropriate growth factors, such as vascular endothelial growth factors, can have an additive effect. A selection of the most effective protocols is discussed in this review.

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Challenges and Solutions for Commercial Scale Manufacturing of Allogeneic Pluripotent Stem Cell Products

Cited by 15 publications

References 27 publications

Whole Heart Engineering: Advances and Challenges

Whole Heart Engineering: Advances and Challenges

Development of a 48-Well Dynamic Suspension Culture System for Pancreatic Differentiation from Human Embryonic Stem Cells

Vascularization is the next challenge for skin tissue engineering as a solution for burn management

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