Marko Närhi

Services for distribution of tissue engineering products and therapies

Purpose – Tissue engineering (TE) offers treatments for chronic, life threatening, degenerative illnesses and possibilities for restoring cellular or organ functions that have been lost due to injuries or hereditary conditions. However, a prerequisite for the use of TE products as part of future therapies is the development of strategies for safe and efficient supply chain management and versatile services spanning from product development to a follow‐up period of possibly decades. The present study aims to explore the future needs for services and extended supply chains for safe delivery of health care, procurement, distribution and long‐term follow‐up of TE products and therapies.Design/methodology/approach – Studies in operational disciplines and coordination systems for different types of supply chains and service networks are used to formulate a framework for developing services throughout product lifecycle. Case examples of TE products are presented to demonstrate complexity, microbial risks, servic...

Monitoring mitochondrial inner membrane potential for detecting early changes in viability of bacterium-infected human bone marrow-derived mesenchymal stem cells

IntroductionOne of the most challenging safety issues in the manufacture of cell based medicinal products is the control of microbial risk as cell-based products cannot undergo terminal sterilization. Accordingly, sensitive and reliable methods for detection of microbial contamination are called for. As mitochondrial function has been shown to correlate with the viability and functionality of human mesenchymal stem cells (hMSCs) we have studied the use of a mitochondrial inner membrane potential sensitive dye for detecting changes in the function of mitochondria following infection by bacteria.MethodsThe effect of bacterial contamination on the viability of bone marrow-derived mesenchymal stem cells (BMMSCs) was studied. BMMSC lines were infected with three different bacterial species, namely two strains of Pseudomonas aeruginosa, three strains of Staphylococcus aureus, and three strains of Staphylococcus epidermidis. The changes in viability of the BMMSCs after bacterial infection were studied by staining with Trypan blue, by morphological analysis and by monitoring of the mitochondrial inner membrane potential.ResultsMicroscopy and viability assessment by Trypan blue staining showed that even the lowest bacterial inocula caused total dissipation of BMMSCs within 24 hours of infection, similar to the effects seen with bacterial loads which were several magnitudes higher. The first significant signs of damage induced by the pathogens became evident after 6 hours of infection. Early changes in mitochondrial inner membrane potential of BMMSCs were evident after 4 hours of infection even though no visible changes in viability of the BMMSCs could be seen.ConclusionsEven low levels of bacterial contamination can cause a significant change in the viability of BMMSCs. Moreover, monitoring the depolarization of the mitochondrial inner membrane potential may provide a rapid tool for early detection of cellular damage induced by microbial infection. Accordingly, mitochondrial analyses offer sensitive tools for quality control and monitoring of safety and efficacy of cellular therapy products.

Regulation of cell-based therapeutic products intended for human applications in the EU

AIMS Recent developments in the field of cell-based therapeutic products (CBTPs) have forced the EU to revise its legislation on therapeutic products by enacting several new legal instruments. In this study, we investigate how CBTPs are regulated and what determines their regulatory classification. Furthermore, we compare the regulatory burden between CBTPs in different product categories. MATERIALS & METHODS Product categories covering CBTPs were identified and characteristics critical for the regulatory classification of a CBTP were determined in each category. The effect of the critical characteristics on the classification was evaluated by constructing a decision tree that covers all possible combinations of the critical characteristics. Differences in the regulatory burden between CBTPs were evaluated by comparing regulations crucial for placing a therapeutic product on the EU market between the product categories. RESULTS Regulation of CBTPs has been divided between the main product categories of the EU legal framework for therapeutic products on the basis of the characteristics of the cells that the CBTPs contain. The regulatory burden is lowest for CBTPs regulated as blood, cells or tissues, and highest for CBTPs regulated as medicinal products. CONCLUSION CBTPs exist in all product categories of the EU legal framework for therapeutic products. However, the current framework does not cover all possible CBTPs. Furthermore, our results indicate that the regulatory burden of a CBTP is related to the risk it may pose to the health and safety of recipients.