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Manufacturing of dental pulp cell-based products from human third molars: current strategies and future investigations.

Ducret M, Fabre H, Degoul O, Atzeni G, McGuckin C, Forraz N, Alliot-Licht B, Mallein-Gerin F, Perrier-Groult E, Farges JC - Front Physiol (2015)

Bottom Line: In this context, the tooth has recently emerged as a valuable source of stem/progenitor cells for regenerating orofacial tissues, with easy access to pulp tissue and high differentiation potential of dental pulp mesenchymal cells.However, most dental pulp cell-based medicinal products manufacturing procedures may not be fully satisfactory since they could alter the cells biological properties and the quality of derived products.This article focuses on current manufacturing strategies of dental pulp cell-based medicinal products and proposes a new protocol to improve efficiency, reproducibility and safety of these strategies.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire de Biologie Tissulaire et Ingénierie thérapeutique, UMR5305 Centre National de la Recherche Scientifique/Université Claude Bernard Lyon 1 Lyon, France ; Faculté d'Odontologie, Université de Lyon, Université Claude Bernard Lyon 1 Lyon, France ; Hospices Civils de Lyon, Service de Consultations et Traitements Dentaires Lyon, France.

ABSTRACT
In recent years, mesenchymal cell-based products have been developed to improve surgical therapies aimed at repairing human tissues. In this context, the tooth has recently emerged as a valuable source of stem/progenitor cells for regenerating orofacial tissues, with easy access to pulp tissue and high differentiation potential of dental pulp mesenchymal cells. International guidelines now recommend the use of standardized procedures for cell isolation, storage and expansion in culture to ensure optimal reproducibility, efficacy and safety when cells are used for clinical application. However, most dental pulp cell-based medicinal products manufacturing procedures may not be fully satisfactory since they could alter the cells biological properties and the quality of derived products. Cell isolation, enrichment and cryopreservation procedures combined to long-term expansion in culture media containing xeno- and allogeneic components are known to affect cell phenotype, viability, proliferation and differentiation capacities. This article focuses on current manufacturing strategies of dental pulp cell-based medicinal products and proposes a new protocol to improve efficiency, reproducibility and safety of these strategies.

No MeSH data available.


Important steps during DP-CBMP manufacturing that require modification. Major drawbacks, risks and pitfalls are highlighted for each one, and proposals are made for the development of more GMP-compliant procedures.
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Figure 2: Important steps during DP-CBMP manufacturing that require modification. Major drawbacks, risks and pitfalls are highlighted for each one, and proposals are made for the development of more GMP-compliant procedures.

Mentions: DP-CBMP could also be used in biomedical research as components of bioassay kits to investigate the effects of drugs on dental pulp cells in a reproducible “humanized” system (Jurga et al., 2010; Leeb et al., 2011; Forraz et al., 2013). Such kits are reliable preclinical alternatives to animal models in the actual regulatory context. Assessment of the risks related to chemical products' use and screening or testing new therapeutic molecules are indeed extremely complicated and costly. The average costs to take a blockbuster drug to clinical trials are estimated to be around 1 billion euros. Furthermore, the accuracy of toxicological and preclinical studies greatly depends on the experimental animal models used for such evaluations. In particular, rodent species, widely use, are known to only partially mimic the human biological system. Development of DP-CBMP bioassay kits would offer a prime platform to successfully induce dentinogenesis, osteogenesis or neurogenesis in vitro (Zhang et al., 2006; Woloszyk et al., 2014; Jensen et al., 2015; Leijten et al., 2015).


Manufacturing of dental pulp cell-based products from human third molars: current strategies and future investigations.

Ducret M, Fabre H, Degoul O, Atzeni G, McGuckin C, Forraz N, Alliot-Licht B, Mallein-Gerin F, Perrier-Groult E, Farges JC - Front Physiol (2015)

Important steps during DP-CBMP manufacturing that require modification. Major drawbacks, risks and pitfalls are highlighted for each one, and proposals are made for the development of more GMP-compliant procedures.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526817&req=5

Figure 2: Important steps during DP-CBMP manufacturing that require modification. Major drawbacks, risks and pitfalls are highlighted for each one, and proposals are made for the development of more GMP-compliant procedures.
Mentions: DP-CBMP could also be used in biomedical research as components of bioassay kits to investigate the effects of drugs on dental pulp cells in a reproducible “humanized” system (Jurga et al., 2010; Leeb et al., 2011; Forraz et al., 2013). Such kits are reliable preclinical alternatives to animal models in the actual regulatory context. Assessment of the risks related to chemical products' use and screening or testing new therapeutic molecules are indeed extremely complicated and costly. The average costs to take a blockbuster drug to clinical trials are estimated to be around 1 billion euros. Furthermore, the accuracy of toxicological and preclinical studies greatly depends on the experimental animal models used for such evaluations. In particular, rodent species, widely use, are known to only partially mimic the human biological system. Development of DP-CBMP bioassay kits would offer a prime platform to successfully induce dentinogenesis, osteogenesis or neurogenesis in vitro (Zhang et al., 2006; Woloszyk et al., 2014; Jensen et al., 2015; Leijten et al., 2015).

Bottom Line: In this context, the tooth has recently emerged as a valuable source of stem/progenitor cells for regenerating orofacial tissues, with easy access to pulp tissue and high differentiation potential of dental pulp mesenchymal cells.However, most dental pulp cell-based medicinal products manufacturing procedures may not be fully satisfactory since they could alter the cells biological properties and the quality of derived products.This article focuses on current manufacturing strategies of dental pulp cell-based medicinal products and proposes a new protocol to improve efficiency, reproducibility and safety of these strategies.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire de Biologie Tissulaire et Ingénierie thérapeutique, UMR5305 Centre National de la Recherche Scientifique/Université Claude Bernard Lyon 1 Lyon, France ; Faculté d'Odontologie, Université de Lyon, Université Claude Bernard Lyon 1 Lyon, France ; Hospices Civils de Lyon, Service de Consultations et Traitements Dentaires Lyon, France.

ABSTRACT
In recent years, mesenchymal cell-based products have been developed to improve surgical therapies aimed at repairing human tissues. In this context, the tooth has recently emerged as a valuable source of stem/progenitor cells for regenerating orofacial tissues, with easy access to pulp tissue and high differentiation potential of dental pulp mesenchymal cells. International guidelines now recommend the use of standardized procedures for cell isolation, storage and expansion in culture to ensure optimal reproducibility, efficacy and safety when cells are used for clinical application. However, most dental pulp cell-based medicinal products manufacturing procedures may not be fully satisfactory since they could alter the cells biological properties and the quality of derived products. Cell isolation, enrichment and cryopreservation procedures combined to long-term expansion in culture media containing xeno- and allogeneic components are known to affect cell phenotype, viability, proliferation and differentiation capacities. This article focuses on current manufacturing strategies of dental pulp cell-based medicinal products and proposes a new protocol to improve efficiency, reproducibility and safety of these strategies.

No MeSH data available.