Article
Biotechnology & Applied Microbiology
Pedro Silva Couto, Dale J. J. Stibbs, Marco C. C. Rotondi, Yasuhiro Takeuchi, Qasim A. A. Rafiq
Summary: This study demonstrates a scalable manufacturing process using a microcarrier-bioreactor system for the expansion of gene-modified human mesenchymal stromal cells (hMSCs). The transduced and expanded cells met the criteria established by the International Society for Cell and Gene Therapy (ISCT). This work provides a foundation for the scalable manufacturing of gene-modified hMSCs.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Botao Zhang, Qiaohui Lu, Gance Dai, Yi Zhou, Qian Ye, Yan Zhou, Wen-Song Tan
Summary: Computational fluid dynamic simulations were used to investigate the effect of an impeller structure on flow field structure, aggregate formation, and cellular physiological activity in a commercial spinner flask. By designing a modified impeller, the size of aggregates was reduced, promoting cell proliferation and stemness maintenance.
BIORESOURCES AND BIOPROCESSING
(2023)
Article
Medicine, Research & Experimental
Ruslan Rust, Rebecca Z. Weber, Melanie Generali, Debora Kehl, Chantal Bodenmann, Daniela Uhr, Debora Wanner, Kathrin J. Zuercher, Hirohide Saito, Simon P. Hoerstrup, Roger M. Nitsch, Christian Tackenberg
Summary: In this study, transgene- and xeno-free neural progenitor cells (NPCs) were generated for potential clinical applications. These cells had stable gene expression, could be expanded, and spontaneously differentiated into mature neurons. This research presents a valuable tool for safe and effective cell therapies for brain injuries.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Engineering, Biomedical
Aishah Nasir, Jordan Thorpe, Laurence Burroughs, Joris Meurs, Sara Pijuan-Galito, Derek J. Irvine, Morgan R. Alexander, Chris Denning
Summary: This study identified a polymer substrate suitable for culturing human pluripotent stem cells (hPSCs) in completely defined, xenogenic-free conditions, overcoming limitations in cost, scalability, and reproducibility. A novel polymer blend was discovered that supports long-term expansion of hPSCs and can be easily coated onto standard cultureware. Analysis of cell-polymer interactions provided insight into the role of certain proteins in hPSC attachment and signaling, making this a promising and economical platform for clinical-scale application.
ADVANCED HEALTHCARE MATERIALS
(2021)
Article
Multidisciplinary Sciences
Bei Liu, Shi Chen, Yaxing Xu, Yulin Lyu, Jinlin Wang, Yuanyuan Du, Yongcheng Sun, Heming Liu, Haoying Zhou, Weifeng Lai, Anqi Xue, Ming Yin, Cheng Li, Yun Bai, Jun Xu, Hongkui Deng
Summary: The study introduces a chemically defined and xeno-free culture system for culturing and deriving human EPS cells, which can be long-term maintained in vitro with stable genetics and developmental potentials. This system also allows efficient derivation of human EPS cells from human fibroblast through reprogramming, showing promise for future biomedical applications.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Jaakko Saari, Fatima Siddique, Sanna Korpela, Elina Mantyla, Teemu O. Ihalainen, Katri Kaukinen, Katriina Aalto-Setala, Katri Lindfors, Kati Juuti-Uusitalo
Summary: The small intestinal epithelium plays a crucial role in nutrition, drug absorption, and metabolism. By using animal-free components and serum-free method, functional small intestinal epithelial cells can be generated from iPSCs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell & Tissue Engineering
Ying Hua, Kenji Yoshimochi, Junjun Li, Kazuhiro Takekita, Motoshi Shimotsuma, Lingjun Li, Xiang Qu, Jingbo Zhang, Yoshiki Sawa, Li Liu, Shigeru Miyagawa
Summary: In this study, a xeno-free ON2/AscleStem PSC medium was developed for the expansion of human-induced pluripotent stem cells (hiPSCs). It was found that hiPSCs cultured in this medium showed normal morphology, high self-renewal and differentiation abilities, and compatibility with different matrices. The hiPSCs grown on gelatin nanofiber showed enhanced growth and stemness. Compared to other media, ON2 medium exhibited higher pluripotency. This study demonstrates the potential of ON2 as a cost-effective and reliable medium for the long-term expansion and maintenance of hiPSCs.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Cell Biology
Jun Ochiai, Larakaye Villanueva, Hope Niihara, Yutaka Niihara, Joan Oliva
Summary: This study developed a method to engineer multilayer adipose stem cell cell sheets (ASCCSs) using chemically defined/serum-free culture media, which can differentiate into osteoblasts and chondrocytes. The number of cells per cell sheet was estimated using cell sheet transmittance, providing important non-invasive information.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Nutrition & Dietetics
Dimitrios Tzimorotas, Nina Therese Solberg, R. Christel Andreassen, Panagiota Moutsatsou, Vincent Bodiou, Mona Elisabeth Pedersen, Sissel Beate Ronning
Summary: The study investigates the cultivation of bovine skeletal muscle satellite cells (MuSCs) using low-volume spinner flasks and a benchtop stirred-tank bioreactor (STR). The results demonstrate the successful expansion of primary MuSCs for 38 days in the STR with low initial seeding density and FBS reduction, while maintaining essential cell activities. The cells also retain their functionality after enzymatic dissociation from the microcarriers, and reproducible results are obtained in a separate STR run.
FRONTIERS IN NUTRITION
(2023)
Article
Chemistry, Physical
Yoko Masuzawa, Manabu Kitazawa
Summary: It has been discovered that a series of synthetic sulfated materials can effectively prevent the reduction of bFGF levels in the growth of iPSCs and maintain their cell proliferation. These materials have the potential to improve the expansion culture of iPSCs.
Article
Chemistry, Multidisciplinary
Lingyan Gong, Chayakorn Petchakup, Pujiang Shi, Pei Leng Tan, Lay Poh Tan, Chor Yong Tay, Han Wei Hou
Summary: A novel microfluidic approach for label-free and continuous-flow monitoring of single spheroid/microcarrier based on electrical impedance spectroscopy is reported, with unique impedance signatures identified for optimal spheroid growth and viability monitoring. The platform offers great versatility for multi-parametric analysis of spheroids/microcarriers at high throughput, and can be integrated into bioreactors for long-term and remote monitoring of biomass and cell quality.
Article
Multidisciplinary Sciences
Samuel Nayler, Devika Agarwal, Fabiola Curion, Rory Bowden, Esther B. E. Becker
Summary: By utilizing a robust method without the need for mouse co-culture, three-dimensional cerebellar organoids were successfully generated from human pluripotent stem cells (hPSCs), displaying hallmarks of in vivo cerebellar development. Single-cell profiling revealed the presence and maturity of transcriptionally distinct populations encompassing major cerebellar cell types. This xeno-free human cerebellar organoid model provides valuable insight into cerebellar development and associated disorders through enrichment of cerebellar disease genes in distinct cell populations.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Eiko Shimizu, Hiroki Iguchi, Minh Nguyen Tuyet Le, Yuta Nakamura, Daigo Kobayashi, Yuhei Arai, Kenta Takakura, Seiko Benno, Noriko Yoshida, Masayoshi Tsukahara, Satoshi Haneda, Kouichi Hasegawa
Summary: In this study, a chemically synthetic culture substrate was developed for the expansion and differentiation of human pluripotent stem cells. The substrate exhibited thermotolerance and underwater stability, and could be stored at room temperature. It supported hPSC expansion with similar efficiency to commercial substrates and enabled directed differentiation.
SCIENTIFIC REPORTS
(2022)
Article
Cell & Tissue Engineering
Hassan R. W. Ali, Salwa Suliman, Tarig Al-Hadi Osman, Manuel Carrasco, Ove Bruland, Daniela-Elena Costea, Helge Raeder, Kamal Mustafa
Summary: This study compared the efficiency of using humanized culture conditions and using fetal bovine serum for the generation of iPS cells from different sources and evaluated their stemness. The results showed that the reprogramming efficiency of xeno-free iPS cells was lower compared to xenogenic iPS cells cultured with fetal bovine serum.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Cell & Tissue Engineering
Robert E. Rogers, Andrew Haskell, Berkley P. White, Sujata Dalal, Megan Lopez, Daniel Tahan, Simin Pan, Gagandeep Kaur, Hyemee Kim, Heather Barreda, Susan L. Woodard, Oscar R. Benavides, Jing Dai, Qingguo Zhao, Kristen C. Maitland, Arum Han, Zivko L. Nikolov, Fei Liu, Ryang Hwa Lee, Carl A. Gregory, Roland Kaunas
Summary: The study introduces a platform for scalable expansion and rapid harvest of ihMSCs using GelMA microcarriers, demonstrating robust immunomodulatory activity. This method offers advantages of reproducibility and low cost, making it a significant contribution to the translational potential of ihMSCs.
STEM CELLS TRANSLATIONAL MEDICINE
(2021)
Article
Chemistry, Medicinal
Fuming Zhang, Peng He, Andre L. Rodrigues, Walter Jeske, Ritesh Tandon, John T. Bates, Michael A. Bierdeman, Jawed Fareed, Jonathan Dordick, Robert J. Linhardt
Summary: The study demonstrates that sulfated glycans and highly negatively charged compounds can inhibit the infectivity of SARS-CoV-2. These compounds exhibit strong antiviral activities against both wild-type and Delta S-proteins of the virus in vitro.
Article
Biochemistry & Molecular Biology
Tiago P. Dias, Sandra N. Pinto, Sandra Carvalho, Tiago G. Fernandes, Fabio Fernandes, Maria Margarida Diogo, Maria C. Peleteiro, Manuel Prieto, Joaquim M. S. Cabral
Summary: This study demonstrates the development of a culture system that supports the self-organization of hiPSC-derived cardiac microtissues. It combines manual aggregation, Matrigel encapsulation, and dynamic culture to enhance cardiac differentiation and the formation of organized structures. Furthermore, VEGF supplementation enhances the emergence of microvessel-like structures.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biotechnology & Applied Microbiology
Miguel F. Tenreiro, Mariana A. Branco, Joao P. Cotovio, Joaquim M. S. Cabral, Tiago G. Fernandes, Maria Margarida Diogo
Summary: Human adult stem cells and patient-derived induced pluripotent stem cells are valuable tools for studying human biology, development, and disease. Organoids, which are organ-like structures created from stem cell derivatives, have revolutionized the field. However, there are still limitations such as variability, limited function, and small size. In this article, we summarize the latest technologies that aim to improve the biological fidelity and physiological relevance of organoids, and discuss their potential applications.
TRENDS IN BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Mariana A. Branco, Tiago P. Dias, Joaquim M. S. Cabral, Perpetua Pinto-do-O, Maria Margarida Diogo
Summary: In this study, a self-organized human multilineage organoid was developed to recreate the co-emergence of pro-epicardium, septum transversum mesenchyme, and liver bud. The impact of WNT, BMP, and retinoic acid signaling modulation on the specification of multilineage organoids was investigated. Co-culturing these organoids with cardiomyocyte aggregates resulted in the generation of a self-organized heart organoid with an epicardium-like layer surrounding a myocardium-like tissue. These heart organoids recapitulates the impact of epicardial cells on promoting cardiomyocyte proliferation and maturation. This study provides valuable insights into the myocardium-epicardium interaction during heart organogenesis in both healthy and diseased settings.
NATURE COMMUNICATIONS
(2022)
Article
Cell & Tissue Engineering
Tiago P. Dias, Tania Baltazar, Sandra N. Pinto, Tiago G. Fernandes, Fabio Fernandes, Maria Margarida Diogo, Manuel Prieto, Joaquim M. S. Cabral
Summary: A xeno-free differentiation platform for human induced pluripotent stem cells (hiPSCs) was established, allowing efficient differentiation into cardiomyocytes (CMs). The replating step and integration with purification/enrichment metabolic approaches improved CM yield and purity, while maintaining CM sheet integrity and functionality.
STEM CELLS INTERNATIONAL
(2022)
Article
Biotechnology & Applied Microbiology
Ana Fernandes-Platzgummer, Raquel Cunha, Sara Morini, Marta Carvalho, Juan Moreno-Cid, Carmen Garcia, Joaquim M. S. Cabral, Claudia L. da Silva
Summary: This study successfully establishes a serum-/xenogeneic-free microcarrier-based culture system for the cultivation of bone marrow-derived MSC and production of MSC-EVs. Large numbers of cells and EVs were obtained through static culture and continuous perfusion. The size and concentration of EVs were estimated using nanoparticle tracking analysis.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Review
Biochemistry & Molecular Biology
Mariana A. Branco, Tiago C. Nunes, Joaquim M. S. Cabral, Maria Margarida Diogo
Summary: It is now acknowledged that drug use during pregnancy is necessary to prevent or treat illnesses, but there is often a lack of information on teratogenic risk in humans. Animal models have been the main source of data, but their limitations in predicting human outcomes have led to misidentification of teratogenicity. The development of humanized in vitro models, particularly those that replicate important early developmental stages, can overcome these limitations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Sofia A. Vaz, Sara M. Badenes, Helena M. Pinheiro, Rui C. Martins
Summary: The conventional wastewater treatment process is being improved to reduce pollutant content in effluent. Microalgae cultivation on wastewater shows promise in both water purification and nutrient recovery. Further directing algal biomass to anaerobic co-digestion with wastewater sludge improves biogas yield and energy recovery. However, more data on the distribution of carbon, nitrogen, and phosphorus are needed for future studies.
ENVIRONMENTAL TECHNOLOGY & INNOVATION
(2023)
Article
Biochemistry & Molecular Biology
Laura Alves, Vanessa Machado, Joao Botelho, Jose Joao Mendes, Joaquim M. S. Cabral, Claudia L. da Silva, Marta S. Carvalho
Summary: Cell-based therapies using PDLSC may be a promising alternative to MSC(M) and MSC(AT) for periodontal regeneration, as PDLSC showed enhanced proliferative and osteogenic potential. PDLSC expressed osteogenic markers and had higher calcium content and upregulated osteogenic/periodontal genes compared to MSC(M) and MSC(AT). CD146 was specifically expressed by PDLSC, which also had a higher proliferative capacity. However, alkaline phosphatase activity did not increase in PDLSC.
Article
Biochemistry & Molecular Biology
Frederico Barbosa, Fabio F. F. Garrudo, Ana C. Marques, Joaquim M. S. Cabral, Jorge Morgado, Frederico Castelo Ferreira, Joao C. Silva
Summary: This study aimed to develop electroconductive PAN/PEDOT:PSS nanofibers via electrospinning, which can mimic the fibrous extracellular matrix (ECM) of natural tissue and provide a platform for the delivery of exogenous electrical stimulation (ES). The resulting nanofibers were functionalized with apatite-like structures to imitate the inorganic phase of the bone ECM. The mineralized electroconductive nanofibers demonstrated improved biological performance, including enhanced proliferation of cells and up-regulated expression levels of bone marker genes, making them potential electroactive biomimetic scaffolds for bone defect repair.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biotechnology & Applied Microbiology
Claudia C. Miranda, Mariana Ramalho Gomes, Mariana Moco, Joaquim M. S. Cabral, Frederico Castelo Ferreira, Paola Sanjuan-Alberte
Summary: Chronic kidney disease is a global deadly disease and current treatment methods are insufficient. Engineering kidney tissues from induced pluripotent stem cells (iPSCs) could provide a solution, but implementation is challenging due to the complexity of mature kidneys. Electrospinning, a technique using synthetic and natural polymers to create fibers, shows promise in kidney tissue engineering. However, further research is needed to advance the applications of electrospinning in combination with other manufacturing methods.
BIOENGINEERING-BASEL
(2022)
Article
Biotechnology & Applied Microbiology
Pedro M. Neto, Diogo E. S. Nogueira, Yas Hashimura, Sunghoon Jung, Bruno Pedras, Mario N. Berberan-Santos, Tiago Palmeira, Brian Lee, Joaquim M. S. Cabral, Vitor Geraldes, Carlos A. Rodrigues
Summary: In this study, oxygen transport and hydrodynamic flow in the PBS Vertical-Wheel MINI 0.1 bioreactor were characterized using experimental data and computational fluid dynamics simulations. The results provide new insights into oxygen mass transfer and hydrodynamics, and offer a computational model for further studies.
BIOENGINEERING-BASEL
(2022)
Article
Biotechnology & Applied Microbiology
Diana M. C. Marques, Joao C. Silva, Ana Paula Serro, Joaquim M. S. Cabral, Paola Sanjuan-Alberte, Frederico C. Ferreira
Summary: In this study, novel bioinks based on kappa-carrageenan were successfully formulated and used to fabricate 3D scaffolds. The ink formulation and printing parameters were optimized, enabling the manufacturing of complex structures. Mechanical tests and cell viability assays demonstrated the excellent performance of this material, indicating its potential applications in tissue engineering and cellular agriculture.
BIOENGINEERING-BASEL
(2022)