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Manufacturing mesenchymal stromal cells for clinical applications: A survey of Good Manufacturing Practices at U.S. academic centers

  • Donald G. Phinney
    Correspondence
    Correspondence: Donald G. Phinney, PhD, Department of Molecular Medicine, The Scripps Research Institute, Scripps Florida, A215, 130 Scripps Way, Jupiter, FL 33458.
    Affiliations
    Department of Molecular Medicine, The Scripps Research Institute–Scripps Florida, Jupiter, Florida, USA
    Search for articles by this author
  • Jacques Galipeau
    Affiliations
    Department of Medicine and Carbone Cancer Center, University of Wisconsin in Madison, Madison, Wisconsin, USA
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  • MSC COMMITTEE OF THE INTERNATIONAL SOCIETY OF CELL AND GENE THERAPY

      Abstract

      Background aims

      Mesenchymal stromal cells (MSC) have gained prominence in the field of regenerative medicine due to their excellent safety profile in human patients and recently demonstrated efficacy in late-stage clinical studies. A prerequisite to achieving successful MSC-based therapies is the development of large-scale manufacturing processes that preserve the biological potency of the founder cell population. Because no standardized manufacturing process exists for MSCs, understanding differences in these processes among U.S. academic facilities would allow for better comparison of results obtained in the clinical setting.

      Methods

      We collected information through a questionnaire sent to U.S. academic centers that produce MSCs under Good Manufacturing Practice conditions.

      Results

      The survey provided information on the number and geographic location of academic facilities in the United States and major trends in their manufacturing practices. For example, most facilities employed MSCs enriched from bone marrow by plastic adherence and expanded in media supplemented with pooled human platelet lysate. Sterility testing and product identification via cell surface phenotype analysis were commonly reported practices, whereas initial and working cell plating densities, culture duration, product formulation and the intended use of the MSC product were highly variable among facilities. The survey also revealed that although most facilities assessed product potency, the methods used were limited in scope compared with the broad array of intended clinical applications of the product.

      Conclusions

      Survey responses reported herein offer insight into the current best practices used to manufacture MSC-based products in the United States and how these practices may affect product quality and potency. The responses also provide a foundation to establish standardized manufacturing platforms.

      Key Words

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