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Stem Cells and Good Manufacturing Practices pp 25–48Cite as

GMP Tiered Cell Banking of Non-enzymatically Isolated Dermal Progenitor Fibroblasts for Allogenic Regenerative Medicine

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 2286))

Abstract

Non-enzymatically isolated primary dermal progenitor fibroblasts derived from fetal organ donations are ideal cell types for allogenic musculoskeletal regenerative therapeutic applications. These cell types are differentiated, highly proliferative in standard in vitro culture conditions and extremely stable throughout their defined lifespans. Technical simplicity, robustness of bioprocessing and relatively small therapeutic dose requirements enable pragmatic and efficient production of clinical progenitor fibroblast lots under cGMP standards. Herein we describe optimized and standardized monolayer culture expansion protocols using dermal progenitor fibroblasts isolated under a Fetal Transplantation Program for the establishment of GMP tiered Master, Working and End of Production cryopreserved Cell Banks. Safety, stability and quality parameters are assessed through stringent testing of progeny biological materials, in view of clinical application to human patients suffering from diverse cutaneous chronic and acute affections. These methods and approaches, coupled to adequate cell source optimization, enable the obtention of a virtually limitless source of highly consistent and safe biological therapeutic material to be used for innovative regenerative medicine applications.

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Abbreviations

ATMP:

Advanced therapy medicinal product

BPyV:

Bovine polyomavirus

CD:

Cluster of differentiation

cGMP:

Current good manufacturing practices

CMV:

Cytomegalovirus

CPMP:

European Union Committee for Proprietary Medicinal Products

DMEM:

Dulbecco’s modified Eagle medium

DMSO:

Dimethylsulfoxide

DNA:

Deoxyribonucleic acid

D-PBS:

Dulbecco’s phosphate-buffered saline

EBV:

Epstein-Barr virus

EOP:

End of production

EOPCB:

End of Production Cell Bank

FACS:

Fluorescence-activated cell sorting

FBS:

Fetal bovine serum

FDA:

US Food and Drug Administration

GLP:

Good laboratory practices

GMP:

Good manufacturing practices

HAV:

Hepatitis A virus

HBoV:

Human bocavirus

HBV:

Hepatitis B virus

hCMV:

Human cytomegalovirus

HCV:

Hepatitis C virus

HHV-6/7/8:

Human herpes viruses types 6, 7 and 8

HIV-1/2:

Human immunodeficiency viruses types 1 and 2

HLA:

Human leukocyte antigen

HPL:

Human platelet lysate

HPV:

Human papilloma virus

HSA:

Human serum albumin

HTLV-1/2:

Human T-cell leukemia-lymphoma viruses types 1 and 2

HuPyV:

Human polyomavirus

IPC:

In-process control

KIPyV:

KI polyomavirus

MCB:

Master Cell Bank

PCB:

Parental Cell Bank

PCR:

Polymerase chain reaction

PDT:

Population doubling time

PDV:

Population doubling value

PWCB:

Pilot Working Cell Bank

QFPERT:

Quantitative fluorescent product enhanced reverse transcriptase

QRM:

Quality risk management

SOP:

Standard operating procedure

TEM:

Transmission electron microscopy

WCB:

Working Cell Bank

WUPyV:

WU polyomavirus

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Acknowledgments

We would like to thank the S.A.N.T.E and Sandoz Foundations for their commitments to the Fetal Biobanking Program through the years. We would like to thank Mrs. Judith Applegate for her reviewing of spelling and grammar of the manuscript.

Author information

Authors and Affiliations

  1. Regenerative Therapy Unit, Musculoskeletal Medicine Department, Lausanne University Hospital, University of Lausanne, Epalinges, Switzerland

    Alexis Laurent, Corinne Scaletta, Murielle Michetti, Nathalie Hirt-Burri & Lee Ann Applegate

  2. Plastic, Reconstructive & Hand Surgery Service, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland

    Alexis Laurent, Corinne Scaletta, Murielle Michetti, Nathalie Hirt-Burri, Wassim Raffoul & Lee Ann Applegate

  3. Pediatric Surgery Service, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland

    Anthony S. de Buys Roessingh

  4. Oxford Suzhou Center for Advanced Research, Science and Technology Co. Ltd., Oxford University, Suzhou, People’s Republic of China

    Lee Ann Applegate

  5. Competence Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland

    Lee Ann Applegate

Authors
  1. Alexis Laurent
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  2. Corinne Scaletta
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  3. Murielle Michetti
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  4. Nathalie Hirt-Burri
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  5. Anthony S. de Buys Roessingh
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  6. Wassim Raffoul
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  7. Lee Ann Applegate
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Corresponding author

Correspondence to Lee Ann Applegate .

Editor information

Editors and Affiliations

  1. Ottawa, ON, Canada

    Kursad Turksen

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Laurent, A. et al. (2020). GMP Tiered Cell Banking of Non-enzymatically Isolated Dermal Progenitor Fibroblasts for Allogenic Regenerative Medicine. In: Turksen, K. (eds) Stem Cells and Good Manufacturing Practices. Methods in Molecular Biology, vol 2286. Humana, New York, NY. https://doi.org/10.1007/7651_2020_295

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  • DOI: https://doi.org/10.1007/7651_2020_295

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1326-9

  • Online ISBN: 978-1-0716-1327-6

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