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Scalable manufacture of therapeutic mesenchymal stromal cell products on customizable microcarriers in vertical wheel bioreactors that improve direct visualization, product harvest, and cost.
Haskell, Andrew; White, Berkley P; Rogers, Robert E; Goebel, Erin; Lopez, Megan G; Syvyk, Andrew E; de Oliveira, Daniela A; Barreda, Heather A; Benton, Joshua; Benavides, Oscar R; Dalal, Sujata; Bae, EunHye; Zhang, Yu; Maitland, Kristen; Nikolov, Zivko; Liu, Fei; Lee, Ryang Hwa; Kaunas, Roland; Gregory, Carl A.
Afiliación
  • Haskell A; Department of Cell Biology and Genetics, Texas A&M School of Medicine, Bryan, Texas, USA.
  • White BP; Department of Biomedical Engineering, Texas A&M University, College Station, Texas, USA.
  • Rogers RE; Department of Cell Biology and Genetics, Texas A&M School of Medicine, Bryan, Texas, USA.
  • Goebel E; Department of Cell Biology and Genetics, Texas A&M School of Medicine, Bryan, Texas, USA; Department of Biomedical Engineering, Texas A&M University, College Station, Texas, USA.
  • Lopez MG; Department of Cell Biology and Genetics, Texas A&M School of Medicine, Bryan, Texas, USA.
  • Syvyk AE; National Center for Therapeutics Manufacturing, Texas A&M University, College Station, Texas, USA.
  • de Oliveira DA; National Center for Therapeutics Manufacturing, Texas A&M University, College Station, Texas, USA; Biological and Agricultural Engineering, Texas A&M University, College Station, Texas, USA.
  • Barreda HA; Department of Cell Biology and Genetics, Texas A&M School of Medicine, Bryan, Texas, USA.
  • Benton J; Department of Cell Biology and Genetics, Texas A&M School of Medicine, Bryan, Texas, USA.
  • Benavides OR; Department of Biomedical Engineering, Texas A&M University, College Station, Texas, USA.
  • Dalal S; Department of Cell Biology and Genetics, Texas A&M School of Medicine, Bryan, Texas, USA.
  • Bae E; Department of Cell Biology and Genetics, Texas A&M School of Medicine, Bryan, Texas, USA.
  • Zhang Y; Department of Cell Biology and Genetics, Texas A&M School of Medicine, Bryan, Texas, USA.
  • Maitland K; Department of Biomedical Engineering, Texas A&M University, College Station, Texas, USA; Imaging Program, Chan Zuckerberg Initiative, Redwood City, California, USA.
  • Nikolov Z; National Center for Therapeutics Manufacturing, Texas A&M University, College Station, Texas, USA; Biological and Agricultural Engineering, Texas A&M University, College Station, Texas, USA.
  • Liu F; Department of Cell Biology and Genetics, Texas A&M School of Medicine, Bryan, Texas, USA.
  • Lee RH; Department of Cell Biology and Genetics, Texas A&M School of Medicine, Bryan, Texas, USA.
  • Kaunas R; Department of Biomedical Engineering, Texas A&M University, College Station, Texas, USA. Electronic address: rkaunas@tamu.edu.
  • Gregory CA; Department of Cell Biology and Genetics, Texas A&M School of Medicine, Bryan, Texas, USA. Electronic address: cgregory@tamu.edu.
Cytotherapy ; 26(4): 372-382, 2024 04.
Article en En | MEDLINE | ID: mdl-38363250
ABSTRACT
BACKGROUND

AIMS:

Human mesenchymal stromal cells (hMSCs) and their secreted products show great promise for treatment of musculoskeletal injury and inflammatory or immune diseases. However, the path to clinical utilization is hampered by donor-tissue variation and the inability to manufacture clinically relevant yields of cells or their products in a cost-effective manner. Previously we described a method to produce chemically and mechanically customizable gelatin methacryloyl (GelMA) microcarriers for culture of hMSCs. Herein, we demonstrate scalable GelMA microcarrier-mediated expansion of induced pluripotent stem cell (iPSC)-derived hMSCs (ihMSCs) in 500 mL and 3L vertical wheel bioreactors, offering several advantages over conventional microcarrier and monolayer-based expansion strategies.

METHODS:

Human mesenchymal stromal cells derived from induced pluripotent cells were cultured on custom-made spherical gelatin methacryloyl microcarriers in single-use vertical wheel bioreactors (PBS Biotech). Cell-laden microcarriers were visualized using confocal microscopy and elastic light scattering methodologies. Cells were assayed for viability and differentiation potential in vitro by standard methods. Osteogenic cell matrix derived from cells was tested in vitro for osteogenic healing using a rodent calvarial defect assay. Immune modulation was assayed with an in vivo peritonitis model using Zymozan A.

RESULTS:

The optical properties of GelMA microcarriers permit noninvasive visualization of cells with elastic light scattering modalities, and harvest of product is streamlined by microcarrier digestion. At volumes above 500 mL, the process is significantly more cost-effective than monolayer culture. Osteogenic cell matrix derived from ihMSCs expanded on GelMA microcarriers exhibited enhanced in vivo bone regenerative capacity when compared to bone morphogenic protein 2, and the ihMSCs exhibited superior immunosuppressive properties in vivo when compared to monolayer-generated ihMSCs.

CONCLUSIONS:

These results indicate that the cell expansion strategy described here represents a superior approach for efficient generation, monitoring and harvest of therapeutic MSCs and their products.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Técnicas de Cultivo de Célula / Células Madre Mesenquimatosas Tipo de estudio: Health_economic_evaluation Límite: Humans Idioma: En Revista: Cytotherapy Asunto de la revista: TERAPEUTICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Técnicas de Cultivo de Célula / Células Madre Mesenquimatosas Tipo de estudio: Health_economic_evaluation Límite: Humans Idioma: En Revista: Cytotherapy Asunto de la revista: TERAPEUTICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido