FDA regulation of stem cell-based products.

Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, 1401 Rockville Pike, Suite 200N, Mail Code HFM-720, Rockville, MD 20852-1448, USA.
Science (Impact Factor: 31.2). 07/2009; 324(5935):1662-3. DOI: 10.1126/science.1173712
Source: PubMed

ABSTRACT Cell self-renewal and the capacity to differentiate into multiple cell types (pluripotency) are biological attributes casting stem cells as attractive candidates for development of therapies targeting indications that involve functional restoration of damaged tissues. In the United States, clinical trials designed to demonstrate the safety and effectiveness of stem cell-based products are regulated by the U.S. Food and Drug Administration (FDA). To ensure that subjects enrolled in a clinical study involving stem cell-based products are not exposed to significant and unreasonable risk, the FDA reviews medical and scientific information that encompasses delineation of product-specific characteristics and preclinical testing to determine whether there is sufficient safety assurance to permit initiation of human clinical studies.

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    ABSTRACT: Advances in stem cell manufacturing methods have made it possible to produce stem cell-derived cardiac myocytes at industrial scales for in vitro muscle physiology research purposes. Although FDA-mandated quality assurance metrics address safety issues in the manufacture of stem cell-based products, no standardized guidelines currently exist for the evaluation of stem cell-derived myocyte functionality. As a result, it is unclear whether the various stem cell-derived myocyte cell lines on the market perform similarly, or whether any of them accurately recapitulate the characteristics of native cardiac myocytes. We propose a multiparametric quality assessment rubric in which genetic, structural, electrophysiological, and contractile measurements are coupled with comparison against values for these measurements that are representative of the ventricular myocyte phenotype. We demonstrated this procedure using commercially available, mass-produced murine embryonic stem cell- and induced pluripotent stem cell-derived myocytes compared with a neonatal mouse ventricular myocyte target phenotype in coupled in vitro assays.
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    ABSTRACT: Osteogenic differentiation of various adult stem cell populations such as neural crest-derived stem cells is of great interest in context of bone regeneration. Ideally, exogenously differentiation should mimic endogenous differentiation process, which is partly mediated by topological cues. To elucidate the osteoinductive potential of porous substrates with different pore diameters (30 nm, 100 nm), human neural crest-derived stem cells isolated from the inferior nasal turbinate were cultivated on the surface of nanoporous titanium covered membranes without additional chemical or biological osteoinductive cues. As controls, flat titanium without any topological features and osteogenic medium was used. Cultivation of human neural crest-derived stem cells on 30 nm pores resulted in osteogenic differentiation as demonstrated by alkaline phosphatase activity after seven days as well as by calcium deposition after 3 weeks of cultivation. In contrast, cultivation on flat titanium and membranes with 100 nm pores was not sufficient to induce osteogenic differentiation. Moreover, we demonstrate increase of osteogenic transcripts including Osterix, Osteocalcin and up-regulation of Integrin β1 and α2 in 30 nm pore approach only. Thus, transplantation of stem cells pre-cultivated on nanostructured implants might improve the clinical outcome by support of the graft adherence and acceleration of the regeneration process.
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    ABSTRACT: Facing the challenging treatment of neurodegenerative diseases as well as complex craniofacial injuries such as those common after cancer therapy, the field of regenerative medicine increasingly relies on stem cell transplantation strategies. Here, neural crest-derived stem cells (NCSCs) offer many promising applications, although scale up of clinical-grade processes prior to potential transplantations is currently limiting. In this study, we aimed to establish a clinical-grade, cost-reducing cultivation system for NCSCs isolated from the adult human nose using cGMP-grade Afc-FEP bags. We cultivated human neural crest-derived stem cells from inferior turbinate (ITSCs) in a cell culture bag system using AfC-FEP bags in human blood plasma-supplemented medium. Investigations of viability, proliferation and expression profile of bag-cultured ITSCs were followed by DNA-content and telomerase activity determination. Cultivated ITSCs were introduced to directed in vitro differentiation assays to assess their potential for mesodermal and ectodermal differentiation. Mesodermal differentiation was determined using an enzyme activity assay (alkaline phosophatase, ALP), respective stainings (Alizarin Red S, Von Kossa and Oil Red O), and RT-PCR, while immunocytochemistry and synaptic vesicle recycling were applied to assay neuroectodermal differentiation of ITSCs. When cultivated within Afc-FEP bags, ITSCs grew three-dimensionally in a human blood plasma-derived matrix, thereby showing unchanged morphology, proliferation capability, viability and expression profile in comparison to three dimensionally-cultured ITSCs growing in standard cell culture plastics. Genetic stability of bag-cultured ITSCs was further accompanied by unchanged telomerase activity. Importantly, ITSCs retained their potential to differentiate into mesodermal cell types, particularly including ALP-active, Alizarin Red S-, and Von Kossa-positive osteogenic cell types, as well as adipocytes positive in Oil Red O assays. Bag culture further did not affect the potential of ITSCs to undergo differentiation into neuroectodermal cell types coexpressing beta-III-tubulin and MAP2 and exhibiting the capability for synaptic vesicle recycling. Here, we report for the first time the successful cultivation of human NCSCs within cGMP-grade AfC-FEP bags using a human blood plasma-supplemented medium. Our findings particularly demonstrate the unchanged differentiation capability and genetic stability of the cultivated NCSCs, suggesting the great potential of this culture system for future medical applications in the field of regenerative medicine.
    Stem Cell Research & Therapy 03/2014; 5(2):34. · 3.65 Impact Factor

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