“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.

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Available from: Donald Fink
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    • "Since our differentiation system makes it feasible to produce large numbers of CD34 + CD45 + cells that are highly enriched in myeloid and lymphoid progenitors, it opens opportunities for preclinical testing of iPSC-derived blood products in a highly relevant NHP model. Moving artificial blood products into the clinic requires proof-of-concept animal studies and preclinical safety and toxicity assessment of stem cell therapies in animal models before entering into clinical trials (FDA, 2008FDA, , 2013Fink, 2009). Tumorigenicity, biodistribution, and immunogenicity are identified as areas of concern that need to be addressed through in vivo studies (Goldring et al., 2011;Sharpe et al., 2012). "
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    ABSTRACT: Advances in the scalable production of blood cells from induced pluripotent stem cells (iPSCs) open prospects for the clinical translation of de novo generated blood products, and evoke the need for preclinical evaluation of their efficacy, safety, and immunogenicity in large animal models. Due to substantial similarities with humans, the outcomes of cellular therapies in non-human primate (NHP) models can be readily extrapolated to a clinical setting. However, the use of this model is hampered by relatively low efficiency of blood generation and lack of lymphoid potential in NHP-iPSC differentiation cultures. Here, we generated transgene-free iPSCs from different NHP species and showed the efficient induction of mesoderm, myeloid, and lymphoid cells from these iPSCs using a GSK3β inhibitor. Overall, our studies enable scalable production of hematopoietic progenitors from NHP-iPSCs, and lay the foundation for preclinical testing of iPSC-based therapies for blood and immune system diseases in an NHP model.
    Full-text · Article · Feb 2016 · Stem Cell Reports
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    • "Other works then proposed the use of the more upstanding induced pluripotent stem cells (iPSCs), that is, somatic cells that are reprogrammed for pluripotency via the overexpression of a specific set of genes [8] [9] [10] [11]. Nevertheless, the main issue for both ESCs and iPSCs is the ability to form teratomas [12– 14], which are considered a major obstacle for biomedical applications [15]; in addition, iPSCs have also been associated to marked tumorigenic activity [16]. Besides pluripotent SCs, in the adults, many organs posses tissue-specific populations of SCs which can give rise to differentiated cell lineages appropriate for their location, therefore not fulfilling the principle of pluripotency and, with respect to ESCs and iPSCs, being less self-renovating [17]. "
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    ABSTRACT: Accurate and noninvasive stem cell tracking is one of the most important needs in regenerative medicine to determine both stem cell destinations and final differentiation fates, thus allowing a more detailed picture of the mechanisms involved in these therapies. Given the great importance and advances in the field of nanotechnology for stem cell imaging, currently, several nanoparticles have become standardized products and have been undergoing fast commercialization. This review has been intended to summarize the current use of different engineered nanoparticles in stem cell tracking for regenerative medicine purposes, in particular by detailing their main features and exploring their biosafety aspects, the first step for clinical application. Moreover, this review has summarized the advantages and applications of stem cell tracking with nanoparticles in experimental and preclinical studies and investigated present limitations for their employment in the clinical setting.
    Full-text · Article · Jan 2016 · Stem cell International
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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.
    Full-text · Article · Mar 2014 · Stem Cell Research & Therapy
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