NUCEL (Cell and Molecular Therapy Center): A Multidisciplinary Center for Translational Research in Brazil

Abstract

Social and economical development is closely associated with technological innovation and a well-developed biotechnological industry. In the last few years, Brazil's scientific production has been steadily increasing; however, the number of patents is lagging behind, with technological and translational research requiring governmental incentive and reinforcement. The Cell and Molecular Therapy Center (NUCEL) was created to develop activities in the translational research field, addressing concrete problems found in biomedical and veterinary areas and actively searching for solutions by employing a genetic engineering approach to generate cell lines over-expressing recombinant proteins to be transferred to local biotech companies, aiming at furthering the development of a national competence for local production of biopharmaceuticals of widespread use and of life-saving importance. To this end, mammalian cell engineering technologies were used to generate cell lines over-expressing several different recombinant proteins of biomedical and biotechnological interest, namely, recombinant human Amylin/IAPP for diabetes treatment, human FVIII and FIX clotting factors for hemophilia, human and bovine FSH for fertility and reproduction, and human bone repair proteins (BMPs). Expression of some of these proteins is also being sought with the baculovirus/insect cell system (BEVS) which, in many cases, is able to deliver high-yield production of recombinant proteins with biological activity comparable to that of mammalian systems, but in a much more cost-effective manner. Transfer of some of these recombinant products to local Biotech companies has been pursued by taking advantage of the São Paulo State Foundation (FAPESP) and Federal Government (FINEP, CNPq) incentives for joint Research Development and Innovation partnership projects.

A Fusion between Domains of the Human Bone Morphogenetic Protein-2 and Maize 27 kD γ-Zein Accumulates to High Levels in the Endoplasmic Reticulum without Forming Protein Bodies in Transgenic Tobacco

“…Several attempts to express recombinant active hBMPs in different heterologous systems (such as Escherichia coli, P. pastoris , Baculovirus/insect cells, and mammalian cells) have been made (Colin et al, 2008 ). However, the production has encountered difficulties, especially due to the impairment of protein folding, different grade or absence of post-translational modifications and low protein stability (Hazama et al, 1995 ; Pulkki et al, 2011 ; Park et al, 2014 .).…”

In vitro differentiation of cGMP-grade retinal pigmented epithelium from human embryonic stem cells

“…The WA-09 embryonic stem cell lineage [15] was acquired directly from the Wicell Research Institute (WiCell, Madison, WI, USA) and thawed and cultured under current Good Manufacturing Practices (cGMP) conditions at the University of São Paulo (USP) Cell and Molecular Therapy Center (NUCEL) [16]. Pluripotent cell colonies were plated onto hESC-qualified Matrigel (Corning, NY, USA), maintained in mTeSR-1 medium (Stem Cell Technologies, Vancouver BC, Canada) and manually expanded every 4 to 5 days.…”

Bone Morphogenetic Proteins

“…This strategy ensures reliability, efficiency, and high yields. Biologically active BMPs were expressed in several recombinant systems, such as Escherichia coli, Picchia pastoris, Baculovirus/insect cells, and mammalian cells (Colin et al, 2008;Bustos-Valenzuela et al, 2010;Granjeiro et al, 2010). However, for therapeutic purposes, it is necessary to express the protein in large-scale and in a system that ensures biological activity without immunogenicity, imposing the use of eukaryotic expression systems, which are able to glycosylate these BMPs.…”