Development of Human Chondrocyte–Based Medicinal Products for Autologous Cell Therapy

Abstract

A cell therapy is a clinical treatment including an ex vivo cell manipulation step. Such a therapeutical option began more than forty years ago and is now a worldwide reality. Many human cell-based clinical trials have been developed in every medicine’s field mostly to cure diseases where conventional treatments are inadequate. Even though there have been few completed trials and some conflicting results on their effectiveness have been reported, the full potential of cell-based treatments remains to be explored and investigated (Park et al., 2008). Moreover, public expectation for such novel therapies, especially for treating incurable and/or rare diseases, remains high. Nowadays each tissue of the human body, including foetal and embryonic ones, can become a reliable source for cell therapy (Mason & Dunnill, 2009). Cells isolated from a specific source can be used also to cure every other tissue of the body and may be administered alone, in combination with biomaterials, scaffolds, cytokines and growth factors or can be genetically manipulated (gene therapy). Cell administrations can be local or systemic, singles or multiples. Treatments may be autologous or allogeneic (from living or cadaver donors). A cell preparation can be crucial for a treatment such as in bone marrow transplantation or otherwise it may be used as an adjuvant to improve clinical results like in regenerative medicine or to slow down the development of several chronic conditions. Cell effect after treatment can be via the ability to differentiate along several lineages or, as recently highlighted for stem cells, also via the capacity to release anti-inflammatory cytokines, growth factors and proteins, collectively known as paracrine factors, which may modulate the host microenvironment by stimulating endogenous stem cells recruitment, differentiation and angiogenesis, thus acting as real drugs (Yagi et al., 2010). Ex vivo cell manipulation protocols are different, depending on cell source, type, target, disease and Country regulations. Current European cell therapy laws classify manipulation types according to potentially associated risks. Cutting, grinding, shaping, centrifugation, soaking in antibiotic or antimicrobial solutions, sterilization, irradiation, cell separation, concentration or purification, filtering, lyophilization, freezing, cryopreservation and vitrification are considered “minimal manipulations”. On the other