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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.


Standardization of the DP-CBMP manufacturing process. It requires five major steps: tooth selection and use of the easiest technique for pulp recovery (Step 1), HDPC isolation with fast, safe and less expensive procedures (Step 2), cell expansion in defined, serum-free culture conditions with xeno-free reagents (Step 3), advanced monitoring and control of DP-CBMP manufacturing (Step 4), use of clinical-grade DP-CMBP, for immediate implantation, cryobanking or development of a bioassay (Step 5).
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Figure 1: Standardization of the DP-CBMP manufacturing process. It requires five major steps: tooth selection and use of the easiest technique for pulp recovery (Step 1), HDPC isolation with fast, safe and less expensive procedures (Step 2), cell expansion in defined, serum-free culture conditions with xeno-free reagents (Step 3), advanced monitoring and control of DP-CBMP manufacturing (Step 4), use of clinical-grade DP-CMBP, for immediate implantation, cryobanking or development of a bioassay (Step 5).

Mentions: Production and delivery of MSCs should be made in accordance with European Good Manufacturing Practices (GMP), whereas, in the US, it must comply with Current Good Tissue Practice requirements (GTP) (Fekete et al., 2012; Kellathur and Lou, 2012; Sensebé et al., 2013). GMP/GTP require many quality controls regarding donor eligibility, sample recovery, label, transport and receipt, process and storage, laboratory equipment, supplies and reagents, cell-based product distribution to recipient patients and documentation that must be maintained by the handler (Alici and Blomberg, 2010; Abou-El-Enein et al., 2013; Sensebé et al., 2013; Wuchter et al., 2015). These controls make GMP/GTP procedures long and costly, and further studies are encouraged to develop shorter, less expensive and more standardized procedures for DP-CBMP manufacturing (Albuquerque et al., 2014; Eubanks et al., 2014; Huang and Garcia-Godoy, 2014; La Noce et al., 2014; Nakashima and Iohara, 2014; Hilkens et al., 2015). In the present paper, we will firstly review current international guidelines regarding the five manufacturing steps of DP-CBMP (Figure 1), and then we will highlight the drawbacks and potential risks of actual strategies. Finally we will propose modifications of the protocols intended to increase the efficiency, reproducibility and safety of these strategies, from tooth extraction to the harvest of clinical-grade DP-CMBP.


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)

Standardization of the DP-CBMP manufacturing process. It requires five major steps: tooth selection and use of the easiest technique for pulp recovery (Step 1), HDPC isolation with fast, safe and less expensive procedures (Step 2), cell expansion in defined, serum-free culture conditions with xeno-free reagents (Step 3), advanced monitoring and control of DP-CBMP manufacturing (Step 4), use of clinical-grade DP-CMBP, for immediate implantation, cryobanking or development of a bioassay (Step 5).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Standardization of the DP-CBMP manufacturing process. It requires five major steps: tooth selection and use of the easiest technique for pulp recovery (Step 1), HDPC isolation with fast, safe and less expensive procedures (Step 2), cell expansion in defined, serum-free culture conditions with xeno-free reagents (Step 3), advanced monitoring and control of DP-CBMP manufacturing (Step 4), use of clinical-grade DP-CMBP, for immediate implantation, cryobanking or development of a bioassay (Step 5).
Mentions: Production and delivery of MSCs should be made in accordance with European Good Manufacturing Practices (GMP), whereas, in the US, it must comply with Current Good Tissue Practice requirements (GTP) (Fekete et al., 2012; Kellathur and Lou, 2012; Sensebé et al., 2013). GMP/GTP require many quality controls regarding donor eligibility, sample recovery, label, transport and receipt, process and storage, laboratory equipment, supplies and reagents, cell-based product distribution to recipient patients and documentation that must be maintained by the handler (Alici and Blomberg, 2010; Abou-El-Enein et al., 2013; Sensebé et al., 2013; Wuchter et al., 2015). These controls make GMP/GTP procedures long and costly, and further studies are encouraged to develop shorter, less expensive and more standardized procedures for DP-CBMP manufacturing (Albuquerque et al., 2014; Eubanks et al., 2014; Huang and Garcia-Godoy, 2014; La Noce et al., 2014; Nakashima and Iohara, 2014; Hilkens et al., 2015). In the present paper, we will firstly review current international guidelines regarding the five manufacturing steps of DP-CBMP (Figure 1), and then we will highlight the drawbacks and potential risks of actual strategies. Finally we will propose modifications of the protocols intended to increase the efficiency, reproducibility and safety of these strategies, from tooth extraction to the harvest of clinical-grade DP-CMBP.

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.