“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: 33.61). 07/2009; 324(5935):1662-3. DOI: 10.1126/science.1173712
Source: PubMed


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.


Available from: Donald Fink
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    • "Such necessary cultivation procedures greatly increase the risk of transmitting infectious agents [2], such as viruses [30,31] or bacteria [3] together with the transplant. In this regard, the FDA, as well as respective bodies of the European Union (Euro GMP guidelines), prescribe good tissue handling practices in a sterile environment with minimal contamination risk as well as recommend against the use of animal-derived sera [5,12,32]. "
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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. DOI:10.1186/scrt422 · 3.37 Impact Factor
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    • "In response to widespread efforts to commercialize differentiated stem cells (Brower, 1999), the U.S. Food and Drug Administration (FDA) established a set of regulations and guidelines for manufacturing and quality-control evaluations of human cellular and tissue-based products derived from stem cells (FDA, 2011). The recommendations outlined for evaluating differentiated stem cell phenotypes were developed specifically to address patient safety concerns such as tumorigenicity and immunologic incompatibility , due to the initial focus of the industry on regenerative-medicine applications (Fink, 2009). Concerns about patient safety may have slowed the commercialization of regenerative therapies (Fox, 2011), but the use of industrial stem cell-based products for in vitro research, particularly pharmaceutical screening applications (Placzek et al., 2009; Rubin, 2008; Thomson, 2007; Wobus and Löser, 2011), is a promising goal that can potentially be reached in the near term. "
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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.
    Stem Cell Reports 03/2014; 2(3):282-94. DOI:10.1016/j.stemcr.2014.01.015 · 5.37 Impact Factor
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    • "Additionally, the differentiation of stem cell based products that are allogeneic with respect to the recipient results in increased immunologic incompatibility, due to the expression of foreign non-self antigens. In addition, the death of large proportions of the transplanted cell population, not unique to stem cells, may constitute further risk.2) To determine whether it is reasonable to grant permission for a clinical trial to proceed, the FDA evaluates potential risk based on results derived from the analytical assessment of product characteristics, as well as preclinical proof-of-concept and safety testing, which, collectively, are considered within the context of a proposed clinical study.3) "
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    ABSTRACT: Animal models have long been developed for cardiovascular research. These animal models have been helpful in understanding disease, discovering potential therapeutics, and predicting efficacy. Despite many efforts, however, translational study has been underestimated. Recently, investigations have identified stem cell treatment as a potentially promising cell therapy for regenerative medicine, largely because of the stem cell's ability to differentiate into many functional cell types. Stem cells promise a new era of cell-based therapy for salvaging the heart. However, stem cells have the potential risk of tumor formation. These properties of stem cells are considered a major concern over the efficacy of cell therapy. The translational/preclinical study of stem cells is essential but only at the beginning stages. What types of heart disease are indicated for stem cell therapy, what type of stem cell, what type of animal model, how do we deliver stem cells, and how do we improve heart function? These may be the key issues that the settlement of which would facilitate the transition of stem cell research from bench to bedside. In this review article, we discuss state-of-the-art technology in stem cell therapies for cardiovascular diseases.
    Korean Circulation Journal 08/2013; 43(8):511-518. DOI:10.4070/kcj.2013.43.8.511 · 0.75 Impact Factor
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